Healthy
Conditions
Keywords
Relative abuse potential study; oxycodone; nalteone; Opioid-related disorders; drug abusers, Chronic pain
Brief summary
The main purpose of this study is to determine if oxycodone and naltrexone combination capsules (ALO-02) have the potential to be abused.
Detailed description
Abuse Liability Study
Interventions
DRUGPlacebo
Placebo solution + Placebo ALO-02 (intact)
DRUGintact ALO-02 60 mg/7.2 mg
Placebo solution + ALO-02 60 mg/7.2 mg (intact)
DRUGcrushed ALO-02 60 mg/7.2 mg
crushed ALO-02 60 mg/7.2 mg in solution + placebo ALO-02 (intact)
DRUGcrushed oxycodone IR 60 mg
crushed oxycodone immediate-release (IR) 60 mg in solution + placebo ALO-02 (intact)
DRUGcrushed ALO-02 40 mg/4.8 mg
crushed ALO-02 40 mg/4.8 mg in solution + placebo ALO-02 (intact)
DRUGcrushed oxycodone IR 40 mg
crushed oxycodone immediate-release (IR) 40 mg in solution + placebo ALO-02 (intact)
Sponsors
Syneos Health
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects. * Non-dependent, recreational opioid users. (Must use opioid for non-therapeutic purposes on at least 10 occassions within the last year before Screening Visit, and at least once in 8 weeks before the Screening Visit.
Exclusion criteria
* Diagnosis of substance and/or alcohol dependence. * Subject has participated in, is currently participating in, or is seeking treatment for substance and/or alcohol related disorder. * History of sleep apnea. * Positive urine drug screen (UDS) for other that marijuana. * Positive for Hepatitis B or C and HIV on Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Liking: Peak Effect (Emax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase | Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). Peak Effect (Emax) = Maximum observed score. |
| High: Area Under Effect Curve (AUE) From 0-2 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2 hours post-dose | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours. |
| High: Peak Effect (Emax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 0.25, 0.5, 1, 1.5, 2 hours post-dose | Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Feel Sick: Peak Effect (Emax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Feel Sick: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Nausea: Peak Effect (Emax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Nausea: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Sleepy: Peak Effect (Emax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Sleepy: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm)to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Dizzy: Peak Effect (Emax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Dizzy: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Pupillometry: Peak Effect (Emax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. Emax = Maximum observed score. |
| Pupillometry: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. TEmax = Time to maximum observed score. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone. |
| Take Drug Again: Peak Effect (Emax) | 12, 24, 36 hours post-dose | Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score. |
| Take Drug Again: Mean Effect (Emean) | 12, 24, 36 hours post-dose | Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score. |
| Take Drug Again: Minimum Effect (Emin) | 12, 24, 36 hours post-dose | Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score. |
| Take Drug Again Effect at Hours 12, 24 and 36 | 12, 24, 36 hours post-dose | Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score. |
| Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Overall Drug Liking: Peak Effect (Emax) | 12, 24, 36 hours post-dose | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emax = Maximum observed score. |
| Overall Drug Liking: Mean Effect (Emean) | 12, 24, 36 hours post-dose | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emean = Average observed score. |
| Overall Drug Liking: Minimum Effect (Emin) | 12, 24, 36 hours post-dose | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emin= Average observed score. |
| Overall Drug Liking Effect at Hours 12, 24 and 36 | 12, 24, 36 hours post-dose | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). |
| Any Drug Effects: Peak Effect (Emax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Good Drug Effects: Peak Effect (Emax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Bad Drug Effects: Peak Effect (Emax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). |
| Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone. |
| Plasma Terminal Half-Life (t1/2) of Oxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone. |
| Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Participants who received oxycodone were reported. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Area under the plasma concentration time-curve from zero to the last quantifiable concentration (AUClast). Participants who received oxycodone were reported. |
| Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | \[AUC (0 - ∞)dn\]= Dose normalized area under the plasma concentration versus time curve \[AUC(dn)\] from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0- t) plus AUC (t - ∞). Participants who received oxycodone were reported. Participants who received oxycodone were reported. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Screening up to 28 days after last study drug administration (Day 29) | An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 3 - 7 days following last study drug administration. Symptoms of withdrawal following naloxone administration (naloxone challenge phase) were not collected as adverse events unless they met the criteria for an SAE. AEs included SAEs as well as non-serious AEs which occurred during the trial. |
| Number of Participants With Clinically Significant Change in Vital Sign Examinations | Screening up to 7 days following last study drug administration (Day 8) | Vital signs assessment included measurement of heart rate, systolic and diastolic blood pressures, respiratory rate and oral temperature. Criteria for clinically significant change in any vital sign examination was based on investigator's discretion. |
| Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5 hours post-dose in drug discrimination phase; pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in intervention period | End-tidal carbon dioxide concentration in the expired air (EtCO2) was monitored using capnography in a sitting position. Criteria for clinically significant change in EtCO2 was based on investigator's discretion. |
| Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | pre-dose up to 5 hours in drug discrimination phase; pre-dose up to 12 hours in intervention period | Oxygen saturation of hemoglobin in blood (SpO2) was monitored using pulse oximetry continuously for 5 hours following dosing in the drug discrimination phase and continuously for 12 hours following dosing in the treatment phase, or longer at the discretion of the investigator. Individual measurements was collected in a sitting position. If SpO2 fall below 90 percent (%), the investigator might had administered oxygen via nasal cannula at a flow rate sufficient to maintain the SpO2 greater than or equal to 90%. Participants with fall in SpO2 below 90% were reported. |
| Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the left with strong disliking (score of 0 mm) and on the right with strong liking (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x). |
| High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x). |
| Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the left with strong disliking (score of 0 mm) and on the right with strong liking (score of 100 mm). TEmax = Time to maximum observed score. |
| Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | Cmax\[dn\]=Dose normalized maximum observed plasma concentration of participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone. |
| High: Time to Maximum (Peak) Effect (TEmax) | pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
Countries
Canada
Participant flow
Recruitment details
Recreational opioid users who were not dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria, were recruited in this study.
Pre-assignment details
After successful naloxone challenge test, all participants underwent training sessions involving complete pharmacodynamics test battery before the drug discrimination phase, to ensure that participants fully understood how to perform the tests, were comfortable, and attained a stable level of performance on the various performance-based measures.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Included all participants enrolled in the study. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Drug Discrimination Phase: Day 1 | Adverse Event | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Adverse Event | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Did not met entrance criteria | 0 | 9 | 10 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Protocol Violation | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Naloxone Challenge Phase | Adverse Event | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Naloxone Challenge Phase | Did not meet entrance criteria | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Phase: First Intervention | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Treatment Phase: Fourth Intervention | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Treatment Phase: Fourth Intervention | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Phase: Fourth Intervention | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Treatment Phase: Second Intervention | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Phase: Third Intervention | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 75 | 70 / 72 | 7 / 37 | 28 / 36 | 37 / 37 | 26 / 38 | 33 / 37 | 36 / 36 | 10 / 69 |
| serious Total, serious adverse events | 0 / 75 | 1 / 72 | 0 / 37 | 0 / 36 | 0 / 37 | 0 / 38 | 0 / 37 | 0 / 36 | 0 / 69 |
Outcome results
Primary
Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.
Time frame: 0.25, 0.5, 1, 1.5, 2 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 100.004 hours*mm | Standard Deviation 5.1468 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 118.480 hours*mm | Standard Deviation 28.7707 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 141.305 hours*mm | Standard Deviation 32.9203 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 100.188 hours*mm | Standard Deviation 10.6437 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 127.320 hours*mm | Standard Deviation 31.2906 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | 149.484 hours*mm | Standard Deviation 24.1907 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [39.2, 59.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.999495% CI: [-10.1, 10.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12.1, 32.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [17, 37.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12.8, 33.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000595% CI: [8.1, 28.4]Mixed Models Analysis
Primary
Drug Liking: Peak Effect (Emax)
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). Peak Effect (Emax) = Maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose Pharmacodynamic (PD) data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Peak Effect (Emax) | 51.6 mm | Standard Deviation 3.74 |
| ALO-02 40 Mg-C | Drug Liking: Peak Effect (Emax) | 70.1 mm | Standard Deviation 19.23 |
| OXY 40 mg | Drug Liking: Peak Effect (Emax) | 85.5 mm | Standard Deviation 16.11 |
| ALO-02 60 Mg-I | Drug Liking: Peak Effect (Emax) | 59.3 mm | Standard Deviation 15.09 |
| ALO-02 60 mg- C | Drug Liking: Peak Effect (Emax) | 74.4 mm | Standard Deviation 18.1 |
| OXY 60 mg | Drug Liking: Peak Effect (Emax) | 89.7 mm | Standard Deviation 13.59 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [24.4, 36.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.013295% CI: [1.6, 13.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [9.3, 21.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [16.8, 28.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [9.3, 21.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 18.595% CI: [12.5, 24.6]Mixed Models Analysis
Primary
High: Area Under Effect Curve (AUE) From 0-2 Hour
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-2 Hour | 2.496 hours*mm | Standard Deviation 8.3003 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-2 Hour | 55.250 hours*mm | Standard Deviation 54.128 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-2 Hour | 112.082 hours*mm | Standard Deviation 43.7 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-2 Hour | 9.902 hours*mm | Standard Deviation 21.1911 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-2 Hour | 71.254 hours*mm | Standard Deviation 55.9812 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-2 Hour | 117.578 hours*mm | Standard Deviation 42.2152 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [91.6, 124.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.412595% CI: [-9.6, 23.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [29.6, 62.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [52.4, 85.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [40.3, 73.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [36.2, 69]Mixed Models Analysis
Primary
High: Peak Effect (Emax)
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Peak Effect (Emax) | 10.9 mm | Standard Deviation 20.6 |
| ALO-02 40 Mg-C | High: Peak Effect (Emax) | 47.3 mm | Standard Deviation 36.88 |
| OXY 40 mg | High: Peak Effect (Emax) | 77.9 mm | Standard Deviation 25.46 |
| ALO-02 60 Mg-I | High: Peak Effect (Emax) | 21.7 mm | Standard Deviation 35.36 |
| ALO-02 60 mg- C | High: Peak Effect (Emax) | 53.4 mm | Standard Deviation 34.68 |
| OXY 60 mg | High: Peak Effect (Emax) | 84.7 mm | Standard Deviation 23.67 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [51.5, 74.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.040295% CI: [0.6, 24.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [21.1, 44.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [30.9, 54.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [20.3, 43.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [24.6, 48.1]Mixed Models Analysis
Secondary
Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 23.324 hours*mm | Standard Deviation 98.1331 |
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 5.949 hours*mm | Standard Deviation 16.4695 |
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 3.090 hours*mm | Standard Deviation 10.1113 |
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 5.949 hours*mm | Standard Deviation 16.4695 |
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 1.105 hours*mm | Standard Deviation 5.6058 |
| Placebo | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 13.762 hours*mm | Standard Deviation 46.7425 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 140.152 hours*mm | Standard Deviation 147.5551 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 157.059 hours*mm | Standard Deviation 175.7028 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 20.129 hours*mm | Standard Deviation 23.9971 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 57.504 hours*mm | Standard Deviation 57.6543 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 156.652 hours*mm | Standard Deviation 175.1035 |
| ALO-02 40 Mg-C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 157.059 hours*mm | Standard Deviation 175.7028 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 345.488 hours*mm | Standard Deviation 260.3746 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 345.301 hours*mm | Standard Deviation 260.4659 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 40.199 hours*mm | Standard Deviation 20.3489 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 317.270 hours*mm | Standard Deviation 218.4262 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 283.770 hours*mm | Standard Deviation 173.4241 |
| OXY 40 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 112.910 hours*mm | Standard Deviation 41.6661 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 10.734 hours*mm | Standard Deviation 23.0043 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 107.180 hours*mm | Standard Deviation 190.7655 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 53.242 hours*mm | Standard Deviation 99.4186 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 235.117 hours*mm | Standard Deviation 424.9088 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 4.539 hours*mm | Standard Deviation 11.9639 |
| ALO-02 60 Mg-I | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 218.805 hours*mm | Standard Deviation 379.7129 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 186.387 hours*mm | Standard Deviation 173.5877 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 167.137 hours*mm | Standard Deviation 152.8249 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 26.566 hours*mm | Standard Deviation 24.8693 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 69.059 hours*mm | Standard Deviation 55.0442 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 176.199 hours*mm | Standard Deviation 165.0887 |
| ALO-02 60 mg- C | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 184.137 hours*mm | Standard Deviation 172.7494 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 402.703 hours*mm | Standard Deviation 244.275 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 48.328 hours*mm | Standard Deviation 19.8494 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 124.617 hours*mm | Standard Deviation 41.2197 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 354.391 hours*mm | Standard Deviation 184.4799 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 392.828 hours*mm | Standard Deviation 229.3565 |
| OXY 60 mg | Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 402.516 hours*mm | Standard Deviation 244.3471 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [36, 51.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.415495% CI: [-4.6, 11.2]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [13.9, 29.7]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [17.5, 33.3]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12.3, 28.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [11, 26.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [97.1, 131.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.398595% CI: [-9.8, 24.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [38.5, 72.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [48.8, 83]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [38.5, 72.7]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [37, 71.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [248.8, 356.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.082495% CI: [-6.2, 101.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [134.6, 242.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [108, 216]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [87.9, 195.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [81.7, 189.6]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [219.1, 356.1]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00495% CI: [32.9, 169.8]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [150, 287]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [102, 239]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [90.1, 227.1]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [83.7, 220.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [90.1, 281.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [109.2, 300.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [125.2, 316.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [74.1, 265.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [89.9, 281.5]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003395% CI: [49.1, 240.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001795% CI: [65.2, 274.9]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000195% CI: [106.6, 316.2]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [114.5, 324]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.002795% CI: [57.3, 267]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [81.1, 290.7]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.011695% CI: [30.7, 240.4]Mixed Models Analysis
Secondary
Any Drug Effects: Peak Effect (Emax)
Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Drug Effects: Peak Effect (Emax) | 8.8 mm | Standard Deviation 19.43 |
| ALO-02 40 Mg-C | Any Drug Effects: Peak Effect (Emax) | 47.2 mm | Standard Deviation 38.45 |
| OXY 40 mg | Any Drug Effects: Peak Effect (Emax) | 82.4 mm | Standard Deviation 25.27 |
| ALO-02 60 Mg-I | Any Drug Effects: Peak Effect (Emax) | 27.7 mm | Standard Deviation 35.77 |
| ALO-02 60 mg- C | Any Drug Effects: Peak Effect (Emax) | 56.0 mm | Standard Deviation 35.9 |
| OXY 60 mg | Any Drug Effects: Peak Effect (Emax) | 88.7 mm | Standard Deviation 20.52 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [48.8, 73.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003295% CI: [6.4, 31.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [20.5, 45.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [34.8, 59.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [61.1, 86]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [26, 50.8]Mixed Models Analysis
Secondary
Any Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.258 hours |
| ALO-02 40 Mg-C | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 40 mg | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| ALO-02 60 Mg-I | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.758 hours |
| ALO-02 60 mg- C | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.258 hours |
| OXY 60 mg | Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-4.3, -1.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000195% CI: [1.4, 4.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.700595% CI: [-1.7, 1.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.84495% CI: [-1.3, 1.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.729595% CI: [-1.6, 1.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.875795% CI: [-1.3, 1.5]Mixed Models Analysis
Secondary
Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.652 hours*mm | Standard Deviation 3.5995 |
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 1.270 hours*mm | Standard Deviation 5.2494 |
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 2.527 hours*mm | Standard Deviation 7.6234 |
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 2.527 hours*mm | Standard Deviation 7.6234 |
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 10.340 hours*mm | Standard Deviation 44.842 |
| Placebo | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 19.715 hours*mm | Standard Deviation 97.5206 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 8.164 hours*mm | Standard Deviation 18.3516 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 29.984 hours*mm | Standard Deviation 48.2808 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 30.578 hours*mm | Standard Deviation 48.6353 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.977 hours*mm | Standard Deviation 2.9225 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 28.984 hours*mm | Standard Deviation 47.6235 |
| ALO-02 40 Mg-C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 30.203 hours*mm | Standard Deviation 48.481 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 85.852 hours*mm | Standard Deviation 146.125 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 85.477 hours*mm | Standard Deviation 145.5365 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 71.195 hours*mm | Standard Deviation 112.5641 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 60.133 hours*mm | Standard Deviation 104.8279 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 4.359 hours*mm | Standard Deviation 12.9297 |
| OXY 40 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 16.023 hours*mm | Standard Deviation 32.3331 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 41.570 hours*mm | Standard Deviation 88.3012 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 2.359 hours*mm | Standard Deviation 8.9454 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 22.195 hours*mm | Standard Deviation 63.1674 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 169.352 hours*mm | Standard Deviation 379.2034 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 138.039 hours*mm | Standard Deviation 300.2416 |
| ALO-02 60 Mg-I | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.445 hours*mm | Standard Deviation 2.4294 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.918 hours*mm | Standard Deviation 2.4707 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 50.348 hours*mm | Standard Deviation 111.5406 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 4.840 hours*mm | Standard Deviation 10.928 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 38.191 hours*mm | Standard Deviation 83.7177 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 46.691 hours*mm | Standard Deviation 105.0132 |
| ALO-02 60 mg- C | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 51.473 hours*mm | Standard Deviation 113.3471 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 96.715 hours*mm | Standard Deviation 157.0901 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 81.777 hours*mm | Standard Deviation 124.7723 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 102.434 hours*mm | Standard Deviation 167.6105 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 102.621 hours*mm | Standard Deviation 167.6904 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 17.059 hours*mm | Standard Deviation 28.6213 |
| OXY 60 mg | Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.621 hours*mm | Standard Deviation 7.2682 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.035195% CI: [0.2, 6.3]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.875195% CI: [-3.3, 2.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.079595% CI: [-0.3, 5.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.838295% CI: [-2.7, 3.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.028995% CI: [0.4, 6.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.787895% CI: [-2.6, 3.5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001995% CI: [5.6, 24]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.82195% CI: [-8.1, 10.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.009495% CI: [3.1, 21.5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.445495% CI: [-5.6, 12.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.093495% CI: [-1.3, 17.1]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.135895% CI: [-2.2, 16.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000495% CI: [27, 92.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.236595% CI: [-13.1, 52.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.009195% CI: [11.1, 76.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.033595% CI: [2.8, 68.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.066195% CI: [-2.1, 63.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.107495% CI: [-5.9, 59.8]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.006495% CI: [15.8, 94.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.054395% CI: [-0.7, 78.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.013195% CI: [10.7, 89.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.029795% CI: [4.4, 83.5]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.040795% CI: [1.8, 80.8]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.17195% CI: [-12, 67.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.336295% CI: [-106.7, 36.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [55.2, 198.5]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.144995% CI: [-18.5, 124.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.288295% CI: [-33, 110.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.131495% CI: [-16.6, 126.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.580895% CI: [-51.6, 91.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.141595% CI: [-154.6, 22.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001195% CI: [60.7, 237.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.242395% CI: [-35.9, 140.9]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.49895% CI: [-58, 118.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.225395% CI: [-33.9, 142.9]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.794595% CI: [-76.8, 100.1]Mixed Models Analysis
Secondary
Bad Drug Effects: Peak Effect (Emax)
Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Drug Effects: Peak Effect (Emax) | 5.8 mm | Standard Deviation 15.46 |
| ALO-02 40 Mg-C | Bad Drug Effects: Peak Effect (Emax) | 16.4 mm | Standard Deviation 26.76 |
| OXY 40 mg | Bad Drug Effects: Peak Effect (Emax) | 26.5 mm | Standard Deviation 36.6 |
| ALO-02 60 Mg-I | Bad Drug Effects: Peak Effect (Emax) | 20.6 mm | Standard Deviation 35.67 |
| ALO-02 60 mg- C | Bad Drug Effects: Peak Effect (Emax) | 16.9 mm | Standard Deviation 28.85 |
| OXY 60 mg | Bad Drug Effects: Peak Effect (Emax) | 31.4 mm | Standard Deviation 32.67 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.088395% CI: [-1.7, 23.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.024195% CI: [2, 27.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.023595% CI: [2, 27.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.090195% CI: [-1.7, 23.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.131395% CI: [-3, 22.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.098295% CI: [-2, 23.6]Mixed Models Analysis
Secondary
Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.250 hours |
| ALO-02 40 Mg-C | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 40 mg | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.517 hours |
| ALO-02 60 Mg-I | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.308 hours |
| ALO-02 60 mg- C | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 60 mg | Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.758 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.012995% CI: [-5.1, -0.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000395% CI: [2, 6.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.548395% CI: [-1.6, 2.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.528495% CI: [-1.5, 2.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.133195% CI: [-0.5, 3.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.873295% CI: [-2.1, 2.4]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.125 hours*mm | Standard Deviation 0.5425 |
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 0.922 hours*mm | Standard Deviation 3.0851 |
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 1.844 hours*mm | Standard Deviation 6.2523 |
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 1.906 hours*mm | Standard Deviation 6.2536 |
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 10.094 hours*mm | Standard Deviation 49.8279 |
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 19.844 hours*mm | Standard Deviation 102.7158 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 24.008 hours*mm | Standard Deviation 41.3549 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 48.422 hours*mm | Standard Deviation 85.1544 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 50.109 hours*mm | Standard Deviation 88.1834 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 7.117 hours*mm | Standard Deviation 15.3098 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 47.297 hours*mm | Standard Deviation 82.8121 |
| ALO-02 40 Mg-C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 49.922 hours*mm | Standard Deviation 88.2865 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 85.859 hours*mm | Standard Deviation 136.2835 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 85.484 hours*mm | Standard Deviation 136.4813 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 83.266 hours*mm | Standard Deviation 131.6787 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 75.828 hours*mm | Standard Deviation 117.4212 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 10.117 hours*mm | Standard Deviation 15.909 |
| OXY 40 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 28.758 hours*mm | Standard Deviation 39.5123 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 47.684 hours*mm | Standard Deviation 145.0991 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 2.738 hours*mm | Standard Deviation 10.8592 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 23.934 hours*mm | Standard Deviation 82.1109 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 135.559 hours*mm | Standard Deviation 386.0688 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 120.934 hours*mm | Standard Deviation 324.0852 |
| ALO-02 60 Mg-I | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 1.238 hours*mm | Standard Deviation 4.8747 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 6.207 hours*mm | Standard Deviation 12.4631 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 43.754 hours*mm | Standard Deviation 81.6192 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 18.402 hours*mm | Standard Deviation 33.2777 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 41.410 hours*mm | Standard Deviation 79.02 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 42.160 hours*mm | Standard Deviation 79.5674 |
| ALO-02 60 mg- C | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 44.129 hours*mm | Standard Deviation 81.4783 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 122.551 hours*mm | Standard Deviation 150.8804 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 117.738 hours*mm | Standard Deviation 146.9677 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 122.895 hours*mm | Standard Deviation 150.666 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 123.457 hours*mm | Standard Deviation 150.3432 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 35.691 hours*mm | Standard Deviation 44.1487 |
| OXY 60 mg | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 14.043 hours*mm | Standard Deviation 17.1328 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [7.1, 17.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.686895% CI: [-4.1, 6.2]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.005895% CI: [2.2, 12.5]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.022995% CI: [0.8, 11.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.216895% CI: [-1.9, 8.3]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.009695% CI: [1.7, 11.9]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [20, 45.9]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.800995% CI: [-11.2, 14.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.008695% CI: [4.5, 30.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.008995% CI: [4.4, 30]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.422495% CI: [-7.6, 18]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [9.8, 35.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [57.9, 134.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.25395% CI: [-15.8, 59.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [40.5, 116.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.041495% CI: [1.6, 77.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.132995% CI: [-8.9, 66.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.018795% CI: [7.7, 83.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000995% CI: [31.9, 121.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.045695% CI: [0.9, 89.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000495% CI: [37.8, 127.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.081295% CI: [-5, 84.1]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.117495% CI: [-9, 80]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.042795% CI: [1.5, 90.6]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.931895% CI: [-66.9, 73]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00295% CI: [41.2, 179.6]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.022695% CI: [11.6, 151.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.362995% CI: [-37.3, 101.2]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.307795% CI: [-33.4, 105.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.266295% CI: [-30.1, 108.4]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.787595% CI: [-94.7, 71.9]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.006695% CI: [32.6, 197.4]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.05495% CI: [-1.4, 164.9]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.601495% CI: [-60.6, 104.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.388595% CI: [-46.3, 118.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.480195% CI: [-52.9, 112]Mixed Models Analysis
Secondary
Dizzy: Peak Effect (Emax)
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Peak Effect (Emax) | 3.6 mm | Standard Deviation 12.27 |
| ALO-02 40 Mg-C | Dizzy: Peak Effect (Emax) | 23.4 mm | Standard Deviation 32.63 |
| OXY 40 mg | Dizzy: Peak Effect (Emax) | 30.6 mm | Standard Deviation 36.58 |
| ALO-02 60 Mg-I | Dizzy: Peak Effect (Emax) | 12.0 mm | Standard Deviation 28.21 |
| ALO-02 60 mg- C | Dizzy: Peak Effect (Emax) | 19.5 mm | Standard Deviation 31.56 |
| OXY 60 mg | Dizzy: Peak Effect (Emax) | 39.3 mm | Standard Deviation 37.92 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [16.8, 39.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.142195% CI: [-2.8, 19.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000495% CI: [9.5, 32.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.006495% CI: [4.5, 27]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.197495% CI: [-3.9, 18.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000895% CI: [8.3, 30.8]Mixed Models Analysis
Secondary
Dizzy: Time to Maximum (Peak) Effect (TEmax)
Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.250 hours |
| ALO-02 40 Mg-C | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.758 hours |
| OXY 40 mg | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.767 hours |
| ALO-02 60 Mg-I | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.258 hours |
| ALO-02 60 mg- C | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.292 hours |
| OXY 60 mg | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.758 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.549495% CI: [-2.5, 1.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.062695% CI: [-0.1, 3.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.721695% CI: [-1.6, 2.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.364795% CI: [-1, 2.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.445695% CI: [-2.7, 1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.0595% CI: [0, 3.9]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.539 hours*mm | Standard Deviation 3.0494 |
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 0.727 hours*mm | Standard Deviation 4.0198 |
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 0.984 hours*mm | Standard Deviation 4.2307 |
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 0.984 hours*mm | Standard Deviation 4.2307 |
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 8.797 hours*mm | Standard Deviation 44.3081 |
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 18.359 hours*mm | Standard Deviation 97.2004 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 6.582 hours*mm | Standard Deviation 19.7796 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 5.176 hours*mm | Standard Deviation 17.2686 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 3.004 hours*mm | Standard Deviation 14.4372 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 5.176 hours*mm | Standard Deviation 17.2686 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 5.645 hours*mm | Standard Deviation 18.1099 |
| ALO-02 40 Mg-C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.629 hours*mm | Standard Deviation 3.0605 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 13.387 hours*mm | Standard Deviation 40.8525 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 13.387 hours*mm | Standard Deviation 40.8525 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 4.160 hours*mm | Standard Deviation 16.6354 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 13.387 hours*mm | Standard Deviation 40.8525 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 13.387 hours*mm | Standard Deviation 40.8525 |
| OXY 40 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.957 hours*mm | Standard Deviation 3.3182 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 83.449 hours*mm | Standard Deviation 267.7102 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 64.699 hours*mm | Standard Deviation 196.345 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 1.051 hours*mm | Standard Deviation 4.5067 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 12.324 hours*mm | Standard Deviation 61.4559 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 12.949 hours*mm | Standard Deviation 63.8914 |
| ALO-02 60 Mg-I | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.035 hours*mm | Standard Deviation 0.1463 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 7.406 hours*mm | Standard Deviation 22.7994 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 7.594 hours*mm | Standard Deviation 22.9559 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 0.758 hours*mm | Standard Deviation 2.656 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 5.281 hours*mm | Standard Deviation 17.1483 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 6.156 hours*mm | Standard Deviation 19.8004 |
| ALO-02 60 mg- C | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.039 hours*mm | Standard Deviation 0.1435 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 21.855 hours*mm | Standard Deviation 43.9416 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.996 hours*mm | Standard Deviation 3.2217 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 2.762 hours*mm | Standard Deviation 6.8438 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 15.449 hours*mm | Standard Deviation 36.7603 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 19.137 hours*mm | Standard Deviation 42.386 |
| OXY 60 mg | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 19.605 hours*mm | Standard Deviation 42.5054 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.177195% CI: [-0.4, 2.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.394495% CI: [-1.7, 0.7]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.177895% CI: [-0.4, 2.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.39695% CI: [-1.7, 0.7]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.612595% CI: [-0.9, 1.5]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.905995% CI: [-1.1, 1.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.458595% CI: [-2.9, 6.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.898695% CI: [-4.2, 4.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.364195% CI: [-2.5, 6.7]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.967495% CI: [-4.6, 4.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.574495% CI: [-3.2, 5.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.345795% CI: [-2.4, 6.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.666495% CI: [-13.3, 20.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.194995% CI: [-5.8, 28]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.200995% CI: [-6, 28.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.659595% CI: [-13.1, 20.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.317695% CI: [-8.3, 25.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.642395% CI: [-12.9, 20.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.435895% CI: [-10.5, 24.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.178995% CI: [-5.4, 28.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.113195% CI: [-3.3, 31.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.596595% CI: [-12.6, 21.8]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.317595% CI: [-8.5, 25.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.655195% CI: [-13.3, 21]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.035495% CI: [-87.5, -3.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.0195% CI: [13.4, 97]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.537995% CI: [-29, 55.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.876895% CI: [-45.1, 38.5]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.703195% CI: [-33.8, 49.9]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.850795% CI: [-45.8, 37.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.038195% CI: [-121.2, -3.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.031895% CI: [5.7, 122.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.609595% CI: [-43.6, 74.1]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.64795% CI: [-71.9, 44.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.813695% CI: [-51.4, 65.4]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.669995% CI: [-71, 45.7]Mixed Models Analysis
Secondary
Feel Sick: Peak Effect (Emax)
Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Peak Effect (Emax) | 3.1 mm | Standard Deviation 10.8 |
| ALO-02 40 Mg-C | Feel Sick: Peak Effect (Emax) | 5.4 mm | Standard Deviation 15.14 |
| OXY 40 mg | Feel Sick: Peak Effect (Emax) | 8.8 mm | Standard Deviation 25.63 |
| ALO-02 60 Mg-I | Feel Sick: Peak Effect (Emax) | 10.1 mm | Standard Deviation 26.35 |
| ALO-02 60 mg- C | Feel Sick: Peak Effect (Emax) | 2.6 mm | Standard Deviation 7.06 |
| OXY 60 mg | Feel Sick: Peak Effect (Emax) | 11.7 mm | Standard Deviation 28.16 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.455595% CI: [-5.9, 13.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.149595% CI: [-2.5, 16.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.0295% CI: [1.8, 20.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.866895% CI: [-10.3, 8.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.390495% CI: [-5.3, 13.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.652495% CI: [-7.3, 11.6]Mixed Models Analysis
Secondary
Feel Sick: Time to Maximum (Peak) Effect (TEmax)
Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.250 hours |
| ALO-02 40 Mg-C | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 40 mg | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| ALO-02 60 Mg-I | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| ALO-02 60 mg- C | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 60 mg | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.172895% CI: [-3.9, 0.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.261695% CI: [-1, 3.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.730795% CI: [-1.9, 2.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.547395% CI: [-3, 1.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.499995% CI: [-3.1, 1.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.559295% CI: [-3, 1.6]Mixed Models Analysis
Secondary
Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 9.063 hours*mm | Standard Deviation 24.0659 |
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 26.844 hours*mm | Standard Deviation 101.2648 |
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.805 hours*mm | Standard Deviation 3.6598 |
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 17.469 hours*mm | Standard Deviation 51.3009 |
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 3.055 hours*mm | Standard Deviation 10.014 |
| Placebo | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 9.250 hours*mm | Standard Deviation 24.0378 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 56.352 hours*mm | Standard Deviation 55.7819 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 130.758 hours*mm | Standard Deviation 152.6257 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 20.727 hours*mm | Standard Deviation 23.7958 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 148.195 hours*mm | Standard Deviation 183.1627 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 148.883 hours*mm | Standard Deviation 183.8413 |
| ALO-02 40 Mg-C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 148.883 hours*mm | Standard Deviation 183.8413 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 261.813 hours*mm | Standard Deviation 163.8714 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 297.656 hours*mm | Standard Deviation 240.6821 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 40.992 hours*mm | Standard Deviation 19.3835 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 110.430 hours*mm | Standard Deviation 42.2789 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 282.875 hours*mm | Standard Deviation 205.0344 |
| OXY 40 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 297.844 hours*mm | Standard Deviation 240.6209 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 10.543 hours*mm | Standard Deviation 22.1051 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 171.355 hours*mm | Standard Deviation 394.6735 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 5.254 hours*mm | Standard Deviation 12.3129 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 40.418 hours*mm | Standard Deviation 87.9945 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 161.043 hours*mm | Standard Deviation 349.4292 |
| ALO-02 60 Mg-I | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 77.855 hours*mm | Standard Deviation 172.2503 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 71.305 hours*mm | Standard Deviation 58.734 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 159.750 hours*mm | Standard Deviation 156.8189 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 180.875 hours*mm | Standard Deviation 212.9759 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 168.688 hours*mm | Standard Deviation 173.4909 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 28.234 hours*mm | Standard Deviation 25.4785 |
| ALO-02 60 mg- C | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 180.875 hours*mm | Standard Deviation 212.9759 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 44.656 hours*mm | Standard Deviation 19.306 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 380.414 hours*mm | Standard Deviation 261.099 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 380.602 hours*mm | Standard Deviation 261.1626 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 372.414 hours*mm | Standard Deviation 248.2861 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 114.953 hours*mm | Standard Deviation 41.8081 |
| OXY 60 mg | Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 332.352 hours*mm | Standard Deviation 193.5146 |
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.400395% CI: [-9.8, 24.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [26.6, 60.7]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [31.8, 47.2]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.273995% CI: [-3.4, 12]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [8.7, 24.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [19.7, 35]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12.8, 28.2]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12, 27.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [87.7, 121.8]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [51.3, 85.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [37.3, 71.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [36, 70.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [240, 345.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.227795% CI: [-20.3, 84.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [120.5, 225.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [99.1, 204.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [77.2, 182.3]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [70, 175.1]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [228.3, 362.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.041695% CI: [2.7, 136.5]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [137.5, 271.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [93.5, 227.4]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000195% CI: [66.1, 199.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [73.1, 207]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [127.6, 311.3]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.002295% CI: [53.2, 236.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [108.4, 292]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000595% CI: [72.4, 256.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001995% CI: [54.8, 238.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.004995% CI: [40.8, 224.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [108.3, 310.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00595% CI: [44.7, 246.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000195% CI: [99.7, 301.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00395% CI: [53.3, 255.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.004695% CI: [45.9, 247.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.017195% CI: [22.3, 224.3]Mixed Models Analysis
Secondary
Good Drug Effects: Peak Effect (Emax)
Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Drug Effects: Peak Effect (Emax) | 11.6 mm | Standard Deviation 24.91 |
| ALO-02 40 Mg-C | Good Drug Effects: Peak Effect (Emax) | 48.1 mm | Standard Deviation 38.53 |
| OXY 40 mg | Good Drug Effects: Peak Effect (Emax) | 81.8 mm | Standard Deviation 24.54 |
| ALO-02 60 Mg-I | Good Drug Effects: Peak Effect (Emax) | 24.2 mm | Standard Deviation 34.68 |
| ALO-02 60 mg- C | Good Drug Effects: Peak Effect (Emax) | 54.7 mm | Standard Deviation 36.16 |
| OXY 60 mg | Good Drug Effects: Peak Effect (Emax) | 84.3 mm | Standard Deviation 22.53 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [47.4, 72.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.051495% CI: [-0.1, 25.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [17, 42.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [30.3, 55.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [21, 46.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [23.7, 49.1]Mixed Models Analysis
Secondary
Good Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.258 hours |
| ALO-02 40 Mg-C | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 40 mg | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| ALO-02 60 Mg-I | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 0.517 hours |
| ALO-02 60 mg- C | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 60 mg | Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001695% CI: [-3.7, -0.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.010595% CI: [0.4, 3.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.725995% CI: [-1.7, 1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.781395% CI: [-1.6, 1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.523595% CI: [-1.9, 1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.851295% CI: [-1.6, 1.3]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 1.551 hours*mm | Standard Deviation 8.727 |
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 3.309 hours*mm | Standard Deviation 16.0847 |
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 5.801 hours*mm | Standard Deviation 21.1576 |
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 5.801 hours*mm | Standard Deviation 21.1576 |
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 13.613 hours*mm | Standard Deviation 54.7055 |
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 22.988 hours*mm | Standard Deviation 105.8442 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 6.938 hours*mm | Standard Deviation 18.5123 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 17.656 hours*mm | Standard Deviation 40.3906 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 17.844 hours*mm | Standard Deviation 40.3199 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 1.313 hours*mm | Standard Deviation 4.2183 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 17.656 hours*mm | Standard Deviation 40.3906 |
| ALO-02 40 Mg-C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 17.656 hours*mm | Standard Deviation 40.3906 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 52.508 hours*mm | Standard Deviation 132.8214 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 52.508 hours*mm | Standard Deviation 132.8214 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 40.602 hours*mm | Standard Deviation 97.633 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 34.102 hours*mm | Standard Deviation 88.764 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.867 hours*mm | Standard Deviation 13.3986 |
| OXY 40 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 11.500 hours*mm | Standard Deviation 30.788 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 16.340 hours*mm | Standard Deviation 58.2244 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 0.520 hours*mm | Standard Deviation 2.3602 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 12.465 hours*mm | Standard Deviation 46.6764 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 94.777 hours*mm | Standard Deviation 325.6554 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 76.402 hours*mm | Standard Deviation 243.7336 |
| ALO-02 60 Mg-I | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.043 hours*mm | Standard Deviation 0.151 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.281 hours*mm | Standard Deviation 1.0395 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 21.203 hours*mm | Standard Deviation 45.1793 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 3.813 hours*mm | Standard Deviation 11.0316 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 15.453 hours*mm | Standard Deviation 33.4096 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 18.828 hours*mm | Standard Deviation 41.2148 |
| ALO-02 60 mg- C | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 21.391 hours*mm | Standard Deviation 45.4013 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 41.523 hours*mm | Standard Deviation 78.2852 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 39.648 hours*mm | Standard Deviation 75.0136 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 42.992 hours*mm | Standard Deviation 80.0147 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 43.742 hours*mm | Standard Deviation 79.9894 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 9.398 hours*mm | Standard Deviation 19.9006 |
| OXY 60 mg | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 2.797 hours*mm | Standard Deviation 8.7018 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.182895% CI: [-1.1, 5.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.390895% CI: [-5, 1.9]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.251395% CI: [-1.5, 5.5]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.503595% CI: [-4.6, 2.3]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.145295% CI: [-0.9, 6]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.930395% CI: [-3.6, 3.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.028395% CI: [0.9, 16.7]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.486195% CI: [-10.5, 5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.180995% CI: [-2.5, 13.2]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.85695% CI: [-7.1, 8.5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.238595% CI: [-3.1, 12.4]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.347995% CI: [-4.1, 11.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.018595% CI: [4.7, 50.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.547195% CI: [-15.8, 29.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.036795% CI: [1.5, 47.4]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.379795% CI: [-12.6, 32.9]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.155795% CI: [-6.3, 39.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.290495% CI: [-10.5, 34.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.046795% CI: [0.4, 51.6]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.405695% CI: [-14.6, 36]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.073895% CI: [-2.3, 48.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.298795% CI: [-12, 38.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.076395% CI: [-2.4, 48.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.339695% CI: [-13.1, 37.6]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.242595% CI: [-89.1, 22.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.028195% CI: [6.8, 117.5]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.418995% CI: [-33, 78.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.83195% CI: [-49.4, 61.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.216195% CI: [-20.6, 90.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.890595% CI: [-51.5, 59.2]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.159795% CI: [-124.2, 20.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.052595% CI: [-0.8, 142.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.529495% CI: [-49.3, 95.4]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.912695% CI: [-75.7, 67.7]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.341895% CI: [-37.1, 106.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.883395% CI: [-77, 66.4]Mixed Models Analysis
Secondary
Nausea: Peak Effect (Emax)
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Peak Effect (Emax) | 6.1 mm | Standard Deviation 18.9 |
| ALO-02 40 Mg-C | Nausea: Peak Effect (Emax) | 11.5 mm | Standard Deviation 25.07 |
| OXY 40 mg | Nausea: Peak Effect (Emax) | 17.8 mm | Standard Deviation 32.11 |
| ALO-02 60 Mg-I | Nausea: Peak Effect (Emax) | 9.5 mm | Standard Deviation 26.18 |
| ALO-02 60 mg- C | Nausea: Peak Effect (Emax) | 11.3 mm | Standard Deviation 23.47 |
| OXY 60 mg | Nausea: Peak Effect (Emax) | 22.0 mm | Standard Deviation 33.25 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.021795% CI: [2, 24.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.551395% CI: [-7.8, 14.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.046995% CI: [0.2, 22.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.360495% CI: [-6, 16.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.272595% CI: [-5, 17.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.346195% CI: [-5.8, 16.6]Mixed Models Analysis
Secondary
Nausea: Time to Maximum (Peak) Effect (TEmax)
Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.250 hours |
| ALO-02 40 Mg-C | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 40 mg | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| ALO-02 60 Mg-I | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| ALO-02 60 mg- C | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| OXY 60 mg | Nausea: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.004195% CI: [-6.1, -1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [1.9, 6.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.876595% CI: [-2.7, 2.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.474695% CI: [-1.6, 3.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.460795% CI: [-3.3, 1.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.231695% CI: [-1, 3.9]Mixed Models Analysis
Secondary
Overall Drug Liking Effect at Hours 12, 24 and 36
Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking).
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 49.7 mm | Standard Deviation 11.41 |
| Placebo | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 50.3 mm | Standard Deviation 11.84 |
| Placebo | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 50.6 mm | Standard Deviation 12.78 |
| ALO-02 40 Mg-C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 62.7 mm | Standard Deviation 23.25 |
| ALO-02 40 Mg-C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 61.2 mm | Standard Deviation 26.16 |
| ALO-02 40 Mg-C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 59.9 mm | Standard Deviation 25.2 |
| OXY 40 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 73.2 mm | Standard Deviation 25.03 |
| OXY 40 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 78.5 mm | Standard Deviation 20.86 |
| OXY 40 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 75.5 mm | Standard Deviation 24.26 |
| ALO-02 60 Mg-I | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 51.8 mm | Standard Deviation 21.57 |
| ALO-02 60 Mg-I | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 46.6 mm | Standard Deviation 23.35 |
| ALO-02 60 Mg-I | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 44.8 mm | Standard Deviation 23.62 |
| ALO-02 60 mg- C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 70.1 mm | Standard Deviation 24.53 |
| ALO-02 60 mg- C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 69.8 mm | Standard Deviation 23.19 |
| ALO-02 60 mg- C | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 69.9 mm | Standard Deviation 25.43 |
| OXY 60 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 36 | 77.6 mm | Standard Deviation 23.79 |
| OXY 60 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 12 | 78.1 mm | Standard Deviation 23.99 |
| OXY 60 mg | Overall Drug Liking Effect at Hours 12, 24 and 36 | Hour 24 | 78.1 mm | Standard Deviation 22.95 |
Secondary
Overall Drug Liking: Mean Effect (Emean)
Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emean = Average observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Drug Liking: Mean Effect (Emean) | 50.19 mm | Standard Deviation 11.962 |
| ALO-02 40 Mg-C | Overall Drug Liking: Mean Effect (Emean) | 61.26 mm | Standard Deviation 24.489 |
| OXY 40 mg | Overall Drug Liking: Mean Effect (Emean) | 75.70 mm | Standard Deviation 21.304 |
| ALO-02 60 Mg-I | Overall Drug Liking: Mean Effect (Emean) | 47.72 mm | Standard Deviation 20.715 |
| ALO-02 60 mg- C | Overall Drug Liking: Mean Effect (Emean) | 69.94 mm | Standard Deviation 23.37 |
| OXY 60 mg | Overall Drug Liking: Mean Effect (Emean) | 77.90 mm | Standard Deviation 23.077 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [21.1, 38.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.595195% CI: [-11.2, 6.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.084195% CI: [-1.1, 16.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [11, 28.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001495% CI: [5.7, 23.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.017295% CI: [1.9, 19.6]Mixed Models Analysis
Secondary
Overall Drug Liking: Minimum Effect (Emin)
Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emin= Average observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Drug Liking: Minimum Effect (Emin) | 49.6 mm | Standard Deviation 11.4 |
| ALO-02 40 Mg-C | Overall Drug Liking: Minimum Effect (Emin) | 58.5 mm | Standard Deviation 24.82 |
| OXY 40 mg | Overall Drug Liking: Minimum Effect (Emin) | 71.1 mm | Standard Deviation 25.28 |
| ALO-02 60 Mg-I | Overall Drug Liking: Minimum Effect (Emin) | 43.6 mm | Standard Deviation 23.55 |
| ALO-02 60 mg- C | Overall Drug Liking: Minimum Effect (Emin) | 65.6 mm | Standard Deviation 25.87 |
| OXY 60 mg | Overall Drug Liking: Minimum Effect (Emin) | 74.3 mm | Standard Deviation 23.53 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [21, 39.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.216695% CI: [-15.4, 3.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.077795% CI: [-1, 18]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001195% CI: [6.5, 25.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.008695% CI: [3.3, 22.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.077595% CI: [-0.9, 18]Mixed Models Analysis
Secondary
Overall Drug Liking: Peak Effect (Emax)
Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm = neither like nor dislike, and 100 mm= strong liking). Emax = Maximum observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Drug Liking: Peak Effect (Emax) | 50.8 mm | Standard Deviation 12.8 |
| ALO-02 40 Mg-C | Overall Drug Liking: Peak Effect (Emax) | 64.3 mm | Standard Deviation 24 |
| OXY 40 mg | Overall Drug Liking: Peak Effect (Emax) | 80.8 mm | Standard Deviation 19.51 |
| ALO-02 60 Mg-I | Overall Drug Liking: Peak Effect (Emax) | 52.9 mm | Standard Deviation 21.33 |
| ALO-02 60 mg- C | Overall Drug Liking: Peak Effect (Emax) | 74.0 mm | Standard Deviation 22.44 |
| OXY 60 mg | Overall Drug Liking: Peak Effect (Emax) | 81.6 mm | Standard Deviation 23.15 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003695% CI: [4.4, 22.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [19.6, 37.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.620995% CI: [-6.7, 11.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.099795% CI: [-1.4, 16.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [14.4, 32.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000395% CI: [7.7, 25.5]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 5.160 hours*mm | Standard Deviation 0.7979 |
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 10.164 hours*mm | Standard Deviation 1.589 |
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 41.088 hours*mm | Standard Deviation 6.4135 |
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 62.550 hours*mm | Standard Deviation 9.6352 |
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 125.791 hours*mm | Standard Deviation 19.2063 |
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 188.828 hours*mm | Standard Deviation 29.4183 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 7.564 hours*mm | Standard Deviation 1.3695 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 47.586 hours*mm | Standard Deviation 9.5615 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 162.961 hours*mm | Standard Deviation 29.2071 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 4.022 hours*mm | Standard Deviation 0.7658 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 30.129 hours*mm | Standard Deviation 5.7346 |
| ALO-02 40 Mg-C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 103.711 hours*mm | Standard Deviation 19.5429 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 149.454 hours*mm | Standard Deviation 25.4599 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 91.216 hours*mm | Standard Deviation 17.4729 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 38.713 hours*mm | Standard Deviation 7.6202 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 23.795 hours*mm | Standard Deviation 4.0637 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.599 hours*mm | Standard Deviation 0.6554 |
| OXY 40 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 6.226 hours*mm | Standard Deviation 1.0741 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 46.155 hours*mm | Standard Deviation 8.8631 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 9.889 hours*mm | Standard Deviation 1.6078 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 33.605 hours*mm | Standard Deviation 6.4972 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 130.199 hours*mm | Standard Deviation 23.0719 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 83.530 hours*mm | Standard Deviation 14.693 |
| ALO-02 60 Mg-I | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 5.039 hours*mm | Standard Deviation 0.7893 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.986 hours*mm | Standard Deviation 0.6847 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 102.183 hours*mm | Standard Deviation 17.7741 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 7.384 hours*mm | Standard Deviation 1.2278 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 29.298 hours*mm | Standard Deviation 5.4769 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 46.136 hours*mm | Standard Deviation 8.9456 |
| ALO-02 60 mg- C | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 161.977 hours*mm | Standard Deviation 26.8529 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 35.088 hours*mm | Standard Deviation 6.406 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 21.913 hours*mm | Standard Deviation 3.6297 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 83.832 hours*mm | Standard Deviation 17.641 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 141.638 hours*mm | Standard Deviation 28.1687 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 5.927 hours*mm | Standard Deviation 1.031 |
| OXY 60 mg | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.489 hours*mm | Standard Deviation 0.6738 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.75, -1.42]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.330995% CI: [-0.24, 0.08]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-0.74, -0.42]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.25, -0.92]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-0.59, -0.26]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.21, -0.88]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-4.37, -3.69]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.247595% CI: [-0.54, 0.14]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.96, -1.27]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-2.96, -2.27]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.68, -1]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-2.76, -2.08]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-13.21, -10.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-8.54, -5.93]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-9.2, -6.59]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-12.55, -9.94]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-7.65, -5.05]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-11.67, -9.05]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-13.16, -9.58]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-17.86, -14.28]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-13.53, -9.93]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-17.51, -13.91]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-10.67, -7.09]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-15.99, -12.39]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.878495% CI: [-3.63, 3.11]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-45.02, -38.29]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-23.01, -16.25]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-25.67, -18.9]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-15.86, -9.14]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-23.98, -17.21]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [5.75, 15.54]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-62.63, -52.85]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-27.09, -17.27]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-29.83, -20]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-18.41, -8.64]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-28.62, -18.78]Mixed Models Analysis
Secondary
Pupillometry: Peak Effect (Emax)
Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. Emax = Maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Peak Effect (Emax) | -0.8 mm | Standard Deviation 0.38 |
| ALO-02 40 Mg-C | Pupillometry: Peak Effect (Emax) | -2.0 mm | Standard Deviation 0.71 |
| OXY 40 mg | Pupillometry: Peak Effect (Emax) | -2.7 mm | Standard Deviation 0.72 |
| ALO-02 60 Mg-I | Pupillometry: Peak Effect (Emax) | -2.4 mm | Standard Deviation 0.71 |
| ALO-02 60 mg- C | Pupillometry: Peak Effect (Emax) | -2.1 mm | Standard Deviation 0.63 |
| OXY 60 mg | Pupillometry: Peak Effect (Emax) | -3.0 mm | Standard Deviation 0.76 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-0.69, -0.34]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.86, -1.52]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-0.97, -0.63]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.58, -1.23]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-0.91, -0.56]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-1.46, -1.11]Mixed Models Analysis
Secondary
Pupillometry: Time to Maximum (Peak) Effect (TEmax)
Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 2.275 hours |
| ALO-02 40 Mg-C | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 1.517 hours |
| OXY 40 mg | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 1.517 hours |
| ALO-02 60 Mg-I | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 12.050 hours |
| ALO-02 60 mg- C | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 1.775 hours |
| OXY 60 mg | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 1.533 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-11.9, -7.57]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [2.99, 7.32]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.976695% CI: [-2.13, 2.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-6.78, -2.44]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.724295% CI: [-2.55, 1.78]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-6.62, -2.28]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 3.660 hours*mm | Standard Deviation 11.1947 |
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 17.809 hours*mm | Standard Deviation 35.0786 |
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 57.035 hours*mm | Standard Deviation 117.1422 |
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 68.785 hours*mm | Standard Deviation 151.3384 |
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 107.254 hours*mm | Standard Deviation 299.1972 |
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 135.941 hours*mm | Standard Deviation 402.8944 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 44.152 hours*mm | Standard Deviation 38.4132 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 239.566 hours*mm | Standard Deviation 244.9626 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 299.316 hours*mm | Standard Deviation 316.187 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 9.160 hours*mm | Standard Deviation 12.4734 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 196.691 hours*mm | Standard Deviation 178.559 |
| ALO-02 40 Mg-C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 295.941 hours*mm | Standard Deviation 314.6515 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 414.008 hours*mm | Standard Deviation 349.3465 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 407.820 hours*mm | Standard Deviation 342.4604 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 352.289 hours*mm | Standard Deviation 260.5164 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 295.727 hours*mm | Standard Deviation 204.5401 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 17.555 hours*mm | Standard Deviation 18.6009 |
| OXY 40 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 66.906 hours*mm | Standard Deviation 46.9339 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 195.418 hours*mm | Standard Deviation 271.9999 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 27.512 hours*mm | Standard Deviation 43.9712 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 127.855 hours*mm | Standard Deviation 188.5158 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 382.012 hours*mm | Standard Deviation 585.0876 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 346.949 hours*mm | Standard Deviation 494.5935 |
| ALO-02 60 Mg-I | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 9.004 hours*mm | Standard Deviation 18.9625 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 10.789 hours*mm | Standard Deviation 17.0139 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 341.922 hours*mm | Standard Deviation 407.7011 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 49.125 hours*mm | Standard Deviation 49.5132 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 223.984 hours*mm | Standard Deviation 196.8453 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 270.109 hours*mm | Standard Deviation 253.5547 |
| ALO-02 60 mg- C | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 362.922 hours*mm | Standard Deviation 486.019 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 440.809 hours*mm | Standard Deviation 232.3446 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 378.309 hours*mm | Standard Deviation 195.1978 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 487.559 hours*mm | Standard Deviation 284.8306 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 493.559 hours*mm | Standard Deviation 290.1531 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-2) | 79.848 hours*mm | Standard Deviation 46.1185 |
| OXY 60 mg | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 22.590 hours*mm | Standard Deviation 19.7659 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [6.4, 18.6]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.25595% CI: [-2.6, 9.6]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00195% CI: [4.3, 16.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.066795% CI: [-0.4, 11.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.007595% CI: [2.3, 14.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.135495% CI: [-1.5, 10.7]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [34.2, 67.5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.390595% CI: [-9.4, 24]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000995% CI: [11.9, 45.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [12.9, 46.3]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.007295% CI: [6.3, 39.5]Mixed Models Analysis
Comparison: AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003595% CI: [8.4, 41.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [188.6, 308.3]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.026395% CI: [8.2, 128.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [91.3, 211.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [105.6, 225.3]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001595% CI: [38.3, 157.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [78.7, 198.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [162.8, 319.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.002895% CI: [42.4, 199.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [85.8, 243.1]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [119.4, 276.6]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.005795% CI: [32.8, 189.4]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [89.7, 246.6]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.03695% CI: [8.5, 248.3]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000495% CI: [101.2, 341.7]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.038895% CI: [6.6, 246.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000395% CI: [103.2, 343.2]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.078795% CI: [-12.4, 226.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003395% CI: [61.5, 301]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.168895% CI: [-41.2, 233.3]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001995% CI: [82.6, 358]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.129895% CI: [-31.5, 243.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.002995% CI: [73, 347.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.118995% CI: [-28.3, 245.7]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.028495% CI: [16.4, 290.8]Mixed Models Analysis
Secondary
Sleepy: Peak Effect (Emax)
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Peak Effect (Emax) | 24.7 mm | Standard Deviation 34.06 |
| ALO-02 40 Mg-C | Sleepy: Peak Effect (Emax) | 56.8 mm | Standard Deviation 35.54 |
| OXY 40 mg | Sleepy: Peak Effect (Emax) | 72.0 mm | Standard Deviation 30.57 |
| ALO-02 60 Mg-I | Sleepy: Peak Effect (Emax) | 38.3 mm | Standard Deviation 38.32 |
| ALO-02 60 mg- C | Sleepy: Peak Effect (Emax) | 59.2 mm | Standard Deviation 36.76 |
| OXY 60 mg | Sleepy: Peak Effect (Emax) | 76.1 mm | Standard Deviation 25.88 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [26.4, 51.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.013695% CI: [3.3, 28.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003995% CI: [6.1, 31]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [23.6, 48.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.015795% CI: [2.9, 27.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [20.5, 45.3]Mixed Models Analysis
Secondary
Sleepy: Time to Maximum (Peak) Effect (TEmax)
Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm)to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 0.758 hours |
| ALO-02 40 Mg-C | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 2.025 hours |
| OXY 40 mg | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 2.508 hours |
| ALO-02 60 Mg-I | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 2.000 hours |
| ALO-02 60 mg- C | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 2.017 hours |
| OXY 60 mg | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 2.033 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.032795% CI: [-3.4, -0.1]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001995% CI: [1, 4.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.750895% CI: [-1.9, 1.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.186895% CI: [-0.5, 2.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.994495% CI: [-1.6, 1.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.232295% CI: [-0.6, 2.6]Mixed Models Analysis
Secondary
Take Drug Again Effect at Hours 12, 24 and 36
Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 41.8 mm | Standard Deviation 21.79 |
| Placebo | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 44.0 mm | Standard Deviation 20.63 |
| Placebo | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 42.9 mm | Standard Deviation 20.4 |
| ALO-02 40 Mg-C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 55.5 mm | Standard Deviation 32.73 |
| ALO-02 40 Mg-C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 54.7 mm | Standard Deviation 33.56 |
| ALO-02 40 Mg-C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 53.9 mm | Standard Deviation 32.84 |
| OXY 40 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 76.9 mm | Standard Deviation 26.77 |
| OXY 40 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 79.7 mm | Standard Deviation 22.37 |
| OXY 40 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 76.8 mm | Standard Deviation 25.12 |
| ALO-02 60 Mg-I | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 41.0 mm | Standard Deviation 28.73 |
| ALO-02 60 Mg-I | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 45.8 mm | Standard Deviation 27.53 |
| ALO-02 60 Mg-I | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 41.1 mm | Standard Deviation 28.95 |
| ALO-02 60 mg- C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 69.6 mm | Standard Deviation 28.34 |
| ALO-02 60 mg- C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 68.7 mm | Standard Deviation 30.31 |
| ALO-02 60 mg- C | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 68.1 mm | Standard Deviation 31.99 |
| OXY 60 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 12 | 78.9 mm | Standard Deviation 25.21 |
| OXY 60 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 36 | 76.8 mm | Standard Deviation 25.17 |
| OXY 60 mg | Take Drug Again Effect at Hours 12, 24 and 36 | Hour 24 | 78.3 mm | Standard Deviation 25.17 |
Secondary
Take Drug Again: Mean Effect (Emean)
Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Take Drug Again: Mean Effect (Emean) | 42.90 mm | Standard Deviation 20.002 |
| ALO-02 40 Mg-C | Take Drug Again: Mean Effect (Emean) | 54.71 mm | Standard Deviation 32.635 |
| OXY 40 mg | Take Drug Again: Mean Effect (Emean) | 77.80 mm | Standard Deviation 22.88 |
| ALO-02 60 Mg-I | Take Drug Again: Mean Effect (Emean) | 42.63 mm | Standard Deviation 26.293 |
| ALO-02 60 mg- C | Take Drug Again: Mean Effect (Emean) | 68.78 mm | Standard Deviation 29.883 |
| OXY 60 mg | Take Drug Again: Mean Effect (Emean) | 78.02 mm | Standard Deviation 24.868 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [24, 46]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.981195% CI: [-11.1, 10.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.108395% CI: [-2, 19.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [14.9, 36.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [12.3, 34.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.040895% CI: [0.5, 22.4]Mixed Models Analysis
Secondary
Take Drug Again: Minimum Effect (Emin)
Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Take Drug Again: Minimum Effect (Emin) | 41.1 mm | Standard Deviation 21.6 |
| ALO-02 40 Mg-C | Take Drug Again: Minimum Effect (Emin) | 50.9 mm | Standard Deviation 32.46 |
| OXY 40 mg | Take Drug Again: Minimum Effect (Emin) | 73.2 mm | Standard Deviation 26.92 |
| ALO-02 60 Mg-I | Take Drug Again: Minimum Effect (Emin) | 37.8 mm | Standard Deviation 28.72 |
| ALO-02 60 mg- C | Take Drug Again: Minimum Effect (Emin) | 66.3 mm | Standard Deviation 31.57 |
| OXY 60 mg | Take Drug Again: Minimum Effect (Emin) | 75.2 mm | Standard Deviation 24.85 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [25.2, 48.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.596895% CI: [-14.9, 8.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.147195% CI: [-3.1, 20.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.113695% CI: [-2.3, 21.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [10.6, 34.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.113695% CI: [-2.3, 21.3]Mixed Models Analysis
Secondary
Take Drug Again: Peak Effect (Emax)
Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score.
Time frame: 12, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Take Drug Again: Peak Effect (Emax) | 45.7 mm | Standard Deviation 19.05 |
| ALO-02 40 Mg-C | Take Drug Again: Peak Effect (Emax) | 57.9 mm | Standard Deviation 33.58 |
| OXY 40 mg | Take Drug Again: Peak Effect (Emax) | 83.4 mm | Standard Deviation 20.26 |
| ALO-02 60 Mg-I | Take Drug Again: Peak Effect (Emax) | 48.1 mm | Standard Deviation 28.14 |
| ALO-02 60 mg- C | Take Drug Again: Peak Effect (Emax) | 72.0 mm | Standard Deviation 28.31 |
| OXY 60 mg | Take Drug Again: Peak Effect (Emax) | 81.3 mm | Standard Deviation 25.23 |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [21.8, 43.7]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.643495% CI: [-8.4, 13.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.107295% CI: [-2, 20]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [15.4, 37.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [14.7, 36.6]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.033595% CI: [0.9, 22.9]Mixed Models Analysis
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone
Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.03 hours |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.03 hours |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 37, 37, 35) | 0.559 hours |
| ALO-02 40 Mg-C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 37, 37, 35) | 0.567 hours |
| ALO-02 40 Mg-C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.03 hours |
| ALO-02 40 Mg-C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.07 hours |
| OXY 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 37, 37, 35) | 14.0 hours |
| OXY 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 12.1 hours |
| OXY 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 14.1 hours |
| ALO-02 60 Mg-I | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 0.583 hours |
| ALO-02 60 Mg-I | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 0.600 hours |
| ALO-02 60 Mg-I | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 37, 37, 35) | 0.567 hours |
| ALO-02 60 mg- C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 37, 37, 35) | 0.550 hours |
| ALO-02 60 mg- C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.04 hours |
| ALO-02 60 mg- C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.05 hours |
Other Pre-specified
Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Participants who received oxycodone were reported.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-12) | 319.6 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 87.905 |
| Placebo | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-1) | 45.21 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 19.256 |
| Placebo | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-24) | 356.2 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 104.68 |
| Placebo | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-2) | 103.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 29.463 |
| Placebo | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-8) | 276.8 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 72.686 |
| ALO-02 40 Mg-C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-1) | 37.60 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 13.292 |
| ALO-02 40 Mg-C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-8) | 265.0 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 55.929 |
| ALO-02 40 Mg-C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-2) | 88.12 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 20.159 |
| ALO-02 40 Mg-C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-12) | 314.1 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 72.753 |
| ALO-02 40 Mg-C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-24) | 355.9 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 91.851 |
| OXY 40 mg | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-8) | 79.08 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 19.9 |
| OXY 40 mg | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-1) | 0.02102 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 0.05715 |
| OXY 40 mg | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-2) | 0.7834 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 0.42296 |
| OXY 40 mg | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-12) | 181.6 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 43.706 |
| OXY 40 mg | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-24) | 455.3 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 118.5 |
| ALO-02 60 Mg-I | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-24) | 513.9 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 143.01 |
| ALO-02 60 Mg-I | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-1) | 72.25 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 24.141 |
| ALO-02 60 Mg-I | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-12) | 464.8 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 121.19 |
| ALO-02 60 Mg-I | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-8) | 405.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 98.993 |
| ALO-02 60 Mg-I | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-2) | 157.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 37.317 |
| ALO-02 60 mg- C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-8) | 366.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 88.598 |
| ALO-02 60 mg- C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-12) | 451.5 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 116.62 |
| ALO-02 60 mg- C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-1) | 53.38 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 19.223 |
| ALO-02 60 mg- C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-24) | 527.8 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 149.84 |
| ALO-02 60 mg- C | Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone | AUC (0-2) | 120.0 nanogram*hour/milliliter (ng*hr/mL) | Standard Deviation 34.767 |
Other Pre-specified
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone
Area under the plasma concentration time-curve from zero to the last quantifiable concentration (AUClast). Participants who received oxycodone were reported.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | 361.6 ng*hr/mL | Standard Deviation 108.39 |
| ALO-02 40 Mg-C | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | 361.6 ng*hr/mL | Standard Deviation 95.617 |
| OXY 40 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | 575.8 ng*hr/mL | Standard Deviation 150.15 |
| ALO-02 60 Mg-I | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | 521.0 ng*hr/mL | Standard Deviation 147.32 |
| ALO-02 60 mg- C | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone | 538.6 ng*hr/mL | Standard Deviation 155.71 |
Other Pre-specified
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone
\[AUC (0 - ∞)dn\]= Dose normalized area under the plasma concentration versus time curve \[AUC(dn)\] from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0- t) plus AUC (t - ∞). Participants who received oxycodone were reported. Participants who received oxycodone were reported.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies those participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | 9.079 ng*hr/mL/mg | Standard Deviation 2.712 |
| ALO-02 40 Mg-C | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | 9.085 ng*hr/mL/mg | Standard Deviation 2.3977 |
| OXY 40 mg | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | 10.88 ng*hr/mL/mg | Standard Deviation 2.9327 |
| ALO-02 60 Mg-I | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | 8.718 ng*hr/mL/mg | Standard Deviation 2.4635 |
| ALO-02 60 mg- C | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone | 9.018 ng*hr/mL/mg | Standard Deviation 2.6095 |
Other Pre-specified
Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone
Cmax\[dn\]=Dose normalized maximum observed plasma concentration of participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the Pharmacokinetic (PK) parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.989 nanogram/milliliter/milligram | Standard Deviation 0.62042 |
| Placebo | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.295 nanogram/milliliter/milligram | Standard Deviation 0.37231 |
| Placebo | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 38, 37, 35) | 0.03271 nanogram/milliliter/milligram | Standard Deviation 0.0155 |
| ALO-02 40 Mg-C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 38, 37, 35) | 0.02847 nanogram/milliliter/milligram | Standard Deviation 0.0149 |
| ALO-02 40 Mg-C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.672 nanogram/milliliter/milligram | Standard Deviation 0.40716 |
| ALO-02 40 Mg-C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.123 nanogram/milliliter/milligram | Standard Deviation 0.29543 |
| OXY 40 mg | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 38, 37, 35) | 0.0068 nanogram/milliliter/milligram | Standard Deviation 0.00365 |
| OXY 40 mg | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 0.4978 nanogram/milliliter/milligram | Standard Deviation 0.15863 |
| OXY 40 mg | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 0.3672 nanogram/milliliter/milligram | Standard Deviation 0.18111 |
| ALO-02 60 Mg-I | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.923 nanogram/milliliter/milligram | Standard Deviation 0.54296 |
| ALO-02 60 Mg-I | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.343 nanogram/milliliter/milligram | Standard Deviation 0.36175 |
| ALO-02 60 Mg-I | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 38, 37, 35) | 0.03182 nanogram/milliliter/milligram | Standard Deviation 0.0161 |
| ALO-02 60 mg- C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxymorphone (n= 36, 36, 38, 37, 35) | 0.02419 nanogram/milliliter/milligram | Standard Deviation 0.0118 |
| ALO-02 60 mg- C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Oxycodone (n= 36, 37, 38, 37, 36) | 1.514 nanogram/milliliter/milligram | Standard Deviation 0.42099 |
| ALO-02 60 mg- C | Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone | Noroxycodone (n= 36, 37, 38, 37, 36) | 1.026 nanogram/milliliter/milligram | Standard Deviation 0.33231 |
Other Pre-specified
Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the left with strong disliking (score of 0 mm) and on the right with strong liking (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1202.863 hours*mm | Standard Deviation 9.1566 |
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 399.957 hours*mm | Standard Deviation 8.2973 |
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 50.020 hours*mm | Standard Deviation 2.7443 |
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 1805.113 hours*mm | Standard Deviation 11.7017 |
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 600.645 hours*mm | Standard Deviation 8.198 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 431.973 hours*mm | Standard Deviation 80.0157 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1267.410 hours*mm | Standard Deviation 197.164 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 57.770 hours*mm | Standard Deviation 11.2102 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 1893.848 hours*mm | Standard Deviation 298.919 |
| ALO-02 40 Mg-C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 640.223 hours*mm | Standard Deviation 111.0897 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 492.578 hours*mm | Standard Deviation 112.1774 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1337.016 hours*mm | Standard Deviation 241.1654 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 1955.953 hours*mm | Standard Deviation 326.5777 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 704.328 hours*mm | Standard Deviation 140.9602 |
| OXY 40 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 64.820 hours*mm | Standard Deviation 14.3058 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 616.203 hours*mm | Standard Deviation 130.7196 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 50.703 hours*mm | Standard Deviation 3.2294 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 404.578 hours*mm | Standard Deviation 71.1457 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1203.828 hours*mm | Standard Deviation 289.324 |
| ALO-02 60 Mg-I | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 1783.578 hours*mm | Standard Deviation 361.8779 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1285.289 hours*mm | Standard Deviation 209.4193 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 61.125 hours*mm | Standard Deviation 12.7119 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 1907.414 hours*mm | Standard Deviation 310.0402 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 465.945 hours*mm | Standard Deviation 110.9382 |
| ALO-02 60 mg- C | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 677.320 hours*mm | Standard Deviation 147.0075 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 69.734 hours*mm | Standard Deviation 12.6273 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 1398.836 hours*mm | Standard Deviation 237.2094 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 531.586 hours*mm | Standard Deviation 110.7145 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 2024.711 hours*mm | Standard Deviation 347.2035 |
| OXY 60 mg | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 758.336 hours*mm | Standard Deviation 160.5459 |
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [14.6, 23.5]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.804895% CI: [-3.9, 5]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [4.2, 13.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [6.5, 15.4]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001995% CI: [2.7, 11.6]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00195% CI: [3.2, 12.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [93.6, 161.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.783795% CI: [-29.1, 38.5]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [32, 99.6]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [32.5, 100.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000695% CI: [26.5, 94.1]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.06495% CI: [-1.9, 65.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [94.5, 190.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.516995% CI: [-32.3, 63.9]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001195% CI: [33.2, 129.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001895% CI: [29.1, 125.2]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.009895% CI: [15.6, 111.7]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.107895% CI: [-8.7, 87.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [116.9, 275.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.972695% CI: [-77.7, 80.5]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.00595% CI: [35, 193.2]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.039295% CI: [4.2, 162.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.088395% CI: [-10.4, 147.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.1195% CI: [-14.7, 143.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [138.6, 347.2]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.690695% CI: [-125.3, 83.2]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.025995% CI: [14.5, 223]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.052595% CI: [-1.1, 207.5]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.255895% CI: [-44.1, 164.4]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.095295% CI: [-15.7, 192.9]Mixed Models Analysis
Other Pre-specified
Drug Liking: Time to Maximum (Peak) Effect (TEmax)
Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the left with strong disliking (score of 0 mm) and on the right with strong liking (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 0.267 hours |
| ALO-02 40 Mg-C | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 40 mg | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| ALO-02 60 Mg-I | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 0.758 hours |
| ALO-02 60 mg- C | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 60 mg | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 1.008 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.029895% CI: [-3.3, -0.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000895% CI: [1.1, 4.3]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.64595% CI: [-2, 1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.096295% CI: [-0.2, 2.9]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.19395% CI: [-2.6, 0.5]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.03195% CI: [0.2, 3.3]Mixed Models Analysis
Other Pre-specified
High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 34.137 hours*mm | Standard Deviation 110.6283 |
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 24.199 hours*mm | Standard Deviation 69.6362 |
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 6.512 hours*mm | Standard Deviation 16.7072 |
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 6.512 hours*mm | Standard Deviation 16.7072 |
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 0.785 hours*mm | Standard Deviation 4.1738 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 131.805 hours*mm | Standard Deviation 168.5472 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 131.930 hours*mm | Standard Deviation 168.8668 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 132.305 hours*mm | Standard Deviation 170.0009 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 119.055 hours*mm | Standard Deviation 142.308 |
| ALO-02 40 Mg-C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 20.203 hours*mm | Standard Deviation 22.8004 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 277.715 hours*mm | Standard Deviation 201.686 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 282.902 hours*mm | Standard Deviation 215.7112 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 282.902 hours*mm | Standard Deviation 215.7112 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 40.801 hours*mm | Standard Deviation 20.3235 |
| OXY 40 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 257.527 hours*mm | Standard Deviation 163.9543 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 78.582 hours*mm | Standard Deviation 166.6578 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 4.473 hours*mm | Standard Deviation 11.7536 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 39.145 hours*mm | Standard Deviation 85.5494 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 161.613 hours*mm | Standard Deviation 319.3473 |
| ALO-02 60 Mg-I | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 168.176 hours*mm | Standard Deviation 337.3448 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 171.129 hours*mm | Standard Deviation 180.2282 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 27.465 hours*mm | Standard Deviation 24.2206 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 173.379 hours*mm | Standard Deviation 181.7041 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 153.941 hours*mm | Standard Deviation 150.3297 |
| ALO-02 60 mg- C | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 160.004 hours*mm | Standard Deviation 160.4458 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-1) | 45.836 hours*mm | Standard Deviation 20.4802 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-24) | 362.531 hours*mm | Standard Deviation 252.5074 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-8) | 322.250 hours*mm | Standard Deviation 187.7896 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-36) | 362.531 hours*mm | Standard Deviation 252.5074 |
| OXY 60 mg | High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour | AUE (0-12) | 355.250 hours*mm | Standard Deviation 237.6863 |
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [232.9, 335.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [33.9, 49]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.376395% CI: [-4.2, 10.9]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [10.7, 25.8]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [19.1, 34.1]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [13.1, 28.2]Mixed Models Analysis
Comparison: AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [11.8, 26.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.233695% CI: [-20.4, 82.8]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [115.7, 218.9]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [96.8, 199.7]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [84, 187.2]Mixed Models Analysis
Comparison: AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [62.1, 165]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [213.2, 343.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.032295% CI: [6.1, 136.5]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [130.2, 260.5]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [89.2, 219.3]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [78, 208.4]Mixed Models Analysis
Comparison: AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000295% CI: [61.7, 191.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [118.4, 286.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001595% CI: [53.3, 221.8]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [108.7, 277.2]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000795% CI: [63, 231.1]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000795% CI: [63.9, 232.4]Mixed Models Analysis
Comparison: AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.01195% CI: [25.5, 193.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [107.4, 284.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.003495% CI: [45, 222.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [102.1, 279.8]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.002395% CI: [50.3, 227.6]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.001395% CI: [59, 236.7]Mixed Models Analysis
Comparison: AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.027395% CI: [11.3, 188.6]Mixed Models Analysis
Other Pre-specified
High: Time to Maximum (Peak) Effect (TEmax)
High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | High: Time to Maximum (Peak) Effect (TEmax) | 0.250 hours |
| ALO-02 40 Mg-C | High: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 40 mg | High: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| ALO-02 60 Mg-I | High: Time to Maximum (Peak) Effect (TEmax) | 0.767 hours |
| ALO-02 60 mg- C | High: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
| OXY 60 mg | High: Time to Maximum (Peak) Effect (TEmax) | 1.017 hours |
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: <0.000195% CI: [-5, -1.8]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.000495% CI: [1.3, 4.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.847895% CI: [-1.7, 1.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.619295% CI: [-1.9, 1.2]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.885795% CI: [-1.7, 1.4]Mixed Models Analysis
Comparison: Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.p-value: 0.509295% CI: [-2.1, 1]Mixed Models Analysis
Other Pre-specified
Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol
Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | Naltrexone | 1.389 nanogram per milliliter (ng/mL) | Standard Deviation 1.4633 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol | 8.516 nanogram per milliliter (ng/mL) | Standard Deviation 2.4847 |
| ALO-02 40 Mg-C | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | Naltrexone | 0.01808 nanogram per milliliter (ng/mL) | Standard Deviation 0.11145 |
| ALO-02 40 Mg-C | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol | 0.3012 nanogram per milliliter (ng/mL) | Standard Deviation 1.8325 |
| OXY 40 mg | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | Naltrexone | 2.331 nanogram per milliliter (ng/mL) | Standard Deviation 2.4498 |
| OXY 40 mg | Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol | 13.70 nanogram per milliliter (ng/mL) | Standard Deviation 3.1369 |
Other Pre-specified
Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2)
End-tidal carbon dioxide concentration in the expired air (EtCO2) was monitored using capnography in a sitting position. Criteria for clinically significant change in EtCO2 was based on investigator's discretion.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5 hours post-dose in drug discrimination phase; pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in intervention period
Population: Safety analysis set included all participants who received at least 1 dose of study drug. This outcome measure was not planned to be analyzed in Naloxone Challenge Phase, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| ALO-02 40 Mg-C | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| OXY 40 mg | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| OXY 60 mg | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) | 0 participants |
Other Pre-specified
Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2)
Oxygen saturation of hemoglobin in blood (SpO2) was monitored using pulse oximetry continuously for 5 hours following dosing in the drug discrimination phase and continuously for 12 hours following dosing in the treatment phase, or longer at the discretion of the investigator. Individual measurements was collected in a sitting position. If SpO2 fall below 90 percent (%), the investigator might had administered oxygen via nasal cannula at a flow rate sufficient to maintain the SpO2 greater than or equal to 90%. Participants with fall in SpO2 below 90% were reported.
Time frame: pre-dose up to 5 hours in drug discrimination phase; pre-dose up to 12 hours in intervention period
Population: Safety analysis set included all participants who received at least 1 dose of study drug. This outcome measure was not planned to be analyzed in Naloxone Challenge Phase, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| ALO-02 40 Mg-C | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| OXY 40 mg | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| OXY 60 mg | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) | 0 participants |
Other Pre-specified
Number of Participants With Clinically Significant Change in Vital Sign Examinations
Vital signs assessment included measurement of heart rate, systolic and diastolic blood pressures, respiratory rate and oral temperature. Criteria for clinically significant change in any vital sign examination was based on investigator's discretion.
Time frame: Screening up to 7 days following last study drug administration (Day 8)
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| ALO-02 40 Mg-C | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| OXY 40 mg | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| OXY 60 mg | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
| OXY 60 mg | Number of Participants With Clinically Significant Change in Vital Sign Examinations | 0 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 3 - 7 days following last study drug administration. Symptoms of withdrawal following naloxone administration (naloxone challenge phase) were not collected as adverse events unless they met the criteria for an SAE. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Time frame: Screening up to 28 days after last study drug administration (Day 29)
Population: Safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 5 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ALO-02 40 Mg-C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 70 participants |
| ALO-02 40 Mg-C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 1 participants |
| OXY 40 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 14 participants |
| OXY 40 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 12 participants |
| ALO-02 60 Mg-I | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ALO-02 60 mg- C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 29 participants |
| ALO-02 60 mg- C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| OXY 60 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| OXY 60 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 37 participants |
| ALO-02 60 Mg-I | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ALO-02 60 Mg-I | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 27 participants |
| ALO-02 60 mg- C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 34 participants |
| ALO-02 60 mg- C | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| OXY 60 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 36 participants |
| OXY 60 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
Other Pre-specified
Plasma Terminal Half-Life (t1/2) of Oxycodone
Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies those participants evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Plasma Terminal Half-Life (t1/2) of Oxycodone | 4.470 hours |
| ALO-02 40 Mg-C | Plasma Terminal Half-Life (t1/2) of Oxycodone | 4.240 hours |
| OXY 40 mg | Plasma Terminal Half-Life (t1/2) of Oxycodone | 9.340 hours |
| ALO-02 60 Mg-I | Plasma Terminal Half-Life (t1/2) of Oxycodone | 4.300 hours |
| ALO-02 60 mg- C | Plasma Terminal Half-Life (t1/2) of Oxycodone | 4.195 hours |
Other Pre-specified
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol
Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.
Time frame: pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose
Population: Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | Naltrexone (n= 36, 1, 37) | 0.550 hour |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol (n= 36, 19, 37) | 0.567 hour |
| ALO-02 40 Mg-C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | Naltrexone (n= 36, 1, 37) | 1.58 hour |
| ALO-02 40 Mg-C | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol (n= 36, 19, 37) | 1.55 hour |
| OXY 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | Naltrexone (n= 36, 1, 37) | 0.550 hour |
| OXY 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol | 6-beta-naltrexol (n= 36, 19, 37) | 0.550 hour |