Nondependent Opioid Abuse, Episodic
Conditions
Keywords
abuse potential, abuse liability, recreational opioid use, morphine
Brief summary
The primary purpose of this study is to determine the abuse potential of EMBEDA compared to controlled release morphine when crushed and taken orally by non-dependent recreational opioid users; secondary purposes include to determine the abuse potential of crushed EMBEDA relative to placebo and and to compare the pharmacokinetics and safety of crushed EMBEDA with crushed controlled-release morphine and crushed placebo.
Interventions
DRUGPlacebo
Single-dose, 2 x microcrystalline cellulose (weighed to equal weights of average tablet/capsule of active comparator) mixed with 150 ml artificially sweetened, non-carbonated beverage
DRUGMS Contin (morphine sulfate, controlled release)
Single-dose, 2 x 60 mg morphine sulfate whole tablets manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage
DRUGEMBEDA (morphine sulfate / naltrexone hydrochloride)
Single-dose, solution 2 x 60 mg morphine sulfate with sequestered 2.4 mg Naltrexone hydrochloride whole capsules manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is a recreational opioid user who is NOT physically dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria, and the Naloxone Challenge. A recreational opioid user is defined as recreationally abusing opioids for non-therapeutic purposes (i.e., for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks prior to Visit 1. * Subject is in generally good health as determined by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG).
Exclusion criteria
* Has a history or current diagnosis of substance dependence (excluding caffeine and nicotine), as assessed by the Investigator using the DSM IV-TR criteria. * Has participated in, is currently participating in, or is seeking treatment for substance- and/or alcohol-related disorders (excluding nicotine and caffeine). * History or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. * Has a known allergy or history of hypersensitivity to morphine sulfate, opioids in general, naltrexone hydrochloride (HCl) or similar compounds and/or the known excipients in the investigational drug products. * Has any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or is suspected of having paralytic ileus). * Females who are pregnant, lactating, or are planning to become pregnant during the course of the study. Females with a positive serum pregnancy test at Visit 1 or at any subsequent study visit will be excluded from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs 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 visual analogue scale (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 (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2). |
| Drug Liking: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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). Emax = Maximum observed score. |
| High: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs post-dose | High 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| High: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | High 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). Emax = Maximum observed score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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. |
| High: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs post-dose | High 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| High: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | High 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| High: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | High 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| High: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | High 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| High: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | High 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| High: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | High 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. |
| Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs post-dose | Good effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs post-dose | Good effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | Good effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | Good effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | Good effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Good effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Good Effects: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Good effects 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). Emax = Maximum observed score. |
| Good Effects: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Good effects 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. |
| Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs post-dose | Any effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs post-dose | Any effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | Any effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | Any effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | Any effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Any effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Any Effects: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Any effects 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). Emax = Maximum observed score. |
| Any Effects: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Any effects 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. |
| Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs post-dose | Bad effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs post-dose | Bad effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | Bad effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | Bad effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | Bad effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Bad effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Bad Effects: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Bad effects 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). Emax = Maximum observed score. |
| Bad Effects: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Bad effects 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. |
| Nausea: Area Under Effect Curve (AUE) From 0-1 Hour | Pre-dose, 0.5 and 1 hrs post-dose | Nausea 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Nausea: Area Under Effect Curve (AUE) From 0-2 Hours | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | Nausea 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Nausea: Area Under Effect Curve (AUE) From 0-4 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | Nausea 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Nausea: Area Under Effect Curve (AUE) From 0-8 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | Nausea 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Nausea: Area Under Effect Curve (AUE) From 0-12 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | Nausea 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Nausea: Area Under Effect Curve (AUE) From 0-24 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Nausea 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Nausea: Peak Effect (Emax) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Nausea 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). Emax = Maximum observed score. |
| Nausea: Time to Maximum (Peak) Effect (TEmax) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Nausea 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. |
| Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs 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 a response of '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 hrs (0-2). |
| Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Feel Sick: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. |
| Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. |
| Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr(0-1). |
| Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Sleepy: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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). Emax = Maximum observed score. |
| Sleepy: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5, 1, 1.5 and 2 hrs 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Dizzy: Peak Effect (Emax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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). Emax = Maximum observed score. |
| Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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. |
| Overall Drug Liking Effect at 24 Hours | 24 hrs 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 carryover 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). |
| Take Drug Again Effect at 24 Hours | 24 hrs 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). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour | Pre-dose, 0.5 and 1 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
| Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). |
| Pupillometry: Peak Effect (Emax) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. Emax = Smallest post-dose pupil size. |
| Pupillometry: Time to Maximum (Peak) Effect (TEmax) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. TEmax = Time to smallest post-dose pupil size. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine | Pre-dose, 0.5 and 1 hrs post-dose | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone | Pre-dose, 0.5 and 1 hrs post-dose | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). |
| Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 and 1 hrs 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5 and 1 hrs post-dose | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours | 0.5, 1, 1.5, 2, 3 and 4 hrs 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). |
| Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). |
| Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all participants enrolled in the study. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Drug Discrimination Phase: Day 1 | Discrimination failure | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Backup participant | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Discrimination failure | 0 | 4 | 9 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Physician Decision | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Positive urine drug screen | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Sponsor decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Drug Discrimination Phase: Day 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Naloxone Challenge Phase | Screen failures | 21 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Phase: Second Intervention | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Phase: Third Intervention | Non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Phase: Third Intervention | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 24.7 years STANDARD_DEVIATION 4.52 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 63 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 59 | 1 / 58 | 51 / 59 | 2 / 36 | 10 / 35 | 27 / 33 |
| serious Total, serious adverse events | 0 / 59 | 0 / 58 | 0 / 59 | 0 / 36 | 1 / 35 | 0 / 33 |
Outcome results
Primary
Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours
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 visual analogue scale (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 (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose pharmacodynamic (PD) data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours | 88.3 hrs*mm | Standard Deviation 4.41 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours | 100.3 hrs*mm | Standard Deviation 12.29 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours | 124.7 hrs*mm | Standard Deviation 22.7 |
Comparison: Least square (LS) mean and 95% confidence interval (CI) were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-31.7, -18.1]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000995% CI: [5.1, 18.6]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [30, 43.6]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 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). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Peak Effect (Emax) | 51.6 mm | Standard Deviation 4.21 |
| EMBEDA | Drug Liking: Peak Effect (Emax) | 65.2 mm | Standard Deviation 11.21 |
| Morphine | Drug Liking: Peak Effect (Emax) | 80.6 mm | Standard Deviation 13.09 |
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence. Planned power of at least 89% assumed a mean difference of 15 to 30 points and a standard deviation of paired differences of 15 to 20 points, with conservative multiple comparison adjustment for alpha of 0.025.p-value: <0.000195% CI: [-20.2, -11.1]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [8.9, 18]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [24.6, 33.7]Mixed Models Analysis
Primary
High: Area Under Effect Curve (AUE) From 0-2 Hours
High 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-2 Hours | 2.0 hrs*mm | Standard Deviation 7.34 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-2 Hours | 26.9 hrs*mm | Standard Deviation 27.72 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-2 Hours | 77.5 hrs*mm | Standard Deviation 34.4 |
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-61.2, -41]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [14.5, 34.6]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [65.6, 85.8]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Peak Effect (Emax) | 1.8 mm | Standard Deviation 5.73 |
| EMBEDA | High: Peak Effect (Emax) | 29.2 mm | Standard Deviation 20.72 |
| Morphine | High: Peak Effect (Emax) | 64.1 mm | Standard Deviation 18.85 |
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-42.1, -27.7]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [20.1, 34.4]Mixed Models Analysis
Comparison: LS mean and 95% CI were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [54.9, 69.4]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours
Any effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 7.8 hrs*mm | Standard Deviation 27.85 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 155.4 hrs*mm | Standard Deviation 117.1 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 422.5 hrs*mm | Standard Deviation 136 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-313.2, -223.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [102.1, 191.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [370.2, 460.2]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour
Any effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.8 hrs*mm | Standard Deviation 2.23 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 9.8 hrs*mm | Standard Deviation 12.17 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 22.6 hrs*mm | Standard Deviation 14.89 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-17, -9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [4.8, 12.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [17.8, 25.8]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours
Any effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 10.2 hrs*mm | Standard Deviation 33.8 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 176.4 hrs*mm | Standard Deviation 130.79 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 510.8 hrs*mm | Standard Deviation 194.67 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-395.4, -276.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [106.4, 224.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [442.2, 561]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours
Any effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 1.8 hrs*mm | Standard Deviation 6.41 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 26.7 hrs*mm | Standard Deviation 28.59 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 71.5 hrs*mm | Standard Deviation 33.15 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-55.3, -35.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [14.6, 34.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [59.9, 79.8]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours
Any effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 3.2 hrs*mm | Standard Deviation 11.95 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 63.8 hrs*mm | Standard Deviation 54.35 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 172.2 hrs*mm | Standard Deviation 62.6 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-129.3, -88.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [39.9, 80.4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [148.9, 189.5]Mixed Models Analysis
Secondary
Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours
Any effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 6.4 hrs*mm | Standard Deviation 22.45 |
| EMBEDA | Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 125.6 hrs*mm | Standard Deviation 94.76 |
| Morphine | Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 331.8 hrs*mm | Standard Deviation 105.57 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-242, -172.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [83.9, 153.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [290.8, 360.7]Mixed Models Analysis
Secondary
Any Effects: Peak Effect (Emax)
Any effects 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). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Peak Effect (Emax) | 1.9 mm | Standard Deviation 5.35 |
| EMBEDA | Any Effects: Peak Effect (Emax) | 28.7 mm | Standard Deviation 20.03 |
| Morphine | Any Effects: Peak Effect (Emax) | 62.4 mm | Standard Deviation 18.59 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-40.7, -26.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [19.7, 33.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [53.4, 67.4]Mixed Models Analysis
Secondary
Any Effects: Time to Maximum (Peak) Effect (TEmax)
Any effects 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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Any Effects: Time to Maximum (Peak) Effect (TEmax) | 0.8 hrs | Standard Deviation 0.99 |
| EMBEDA | Any Effects: Time to Maximum (Peak) Effect (TEmax) | 3.1 hrs | Standard Deviation 2.34 |
| Morphine | Any Effects: Time to Maximum (Peak) Effect (TEmax) | 2.8 hrs | Standard Deviation 2.03 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.334595% CI: [-0.4, 1.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1.5, 3.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1.1, 2.8]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine | 551755 hrs*pg/mL | Standard Deviation 476987 |
| EMBEDA | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine | 369270 hrs*pg/mL | Standard Deviation 98821.5 |
Comparison: Natural log transformed AUC (0-∞) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000590% CI: [1.17, 1.49]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone | 3320.90 hrs*pg/mL | Standard Deviation 1616.514 |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol) | 74931.5 hrs*pg/mL | Standard Deviation 25580.1 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine | 303428 hrs*pg/mL | Standard Deviation 86669.9 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine | 288324 hrs*pg/mL | Standard Deviation 81697.4 |
Comparison: Natural log transformed AUC (0-12) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.42590% CI: [0.97, 1.1]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone | 2813.34 hrs*pg/mL | Standard Deviation 1337.306 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol) | 33324.9 hrs*pg/mL | Standard Deviation 7309.76 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Time frame: Pre-dose, 0.5 and 1 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine | 52644.9 hrs*pg/mL | Standard Deviation 19951.6 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine | 67920.1 hrs*pg/mL | Standard Deviation 24702.8 |
Comparison: Natural log transformed AUC (0-1) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000490% CI: [0.69, 0.86]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Time frame: Pre-dose, 0.5 and 1 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone | 619.24 hrs*pg/mL | Standard Deviation 441.602 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1).
Time frame: Pre-dose, 0.5 and 1 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol) | 3934.5 hrs*pg/mL | Standard Deviation 1529.66 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine | 376260 hrs*pg/mL | Standard Deviation 104635.5 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine | 335357 hrs*pg/mL | Standard Deviation 91242.6 |
Comparison: Natural log transformed AUC (0-24) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.020490% CI: [1.03, 1.18]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone | 3159.91 hrs*pg/mL | Standard Deviation 1522.915 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol) | 47809.1 hrs*pg/mL | Standard Deviation 10184.33 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Time frame: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine | 112989 hrs*pg/mL | Standard Deviation 33784.6 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine | 129721 hrs*pg/mL | Standard Deviation 39670.7 |
Comparison: Natural log transformed AUC (0-2) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.006590% CI: [0.79, 0.94]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Time frame: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone | 1270.91 hrs*pg/mL | Standard Deviation 700.063 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2).
Time frame: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol) | 8916.1 hrs*pg/mL | Standard Deviation 2747.62 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine | 197745 hrs*pg/mL | Standard Deviation 54807.4 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine | 199442 hrs*pg/mL | Standard Deviation 60559.8 |
Comparison: Natural log transformed AUC (0-4) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.639990% CI: [0.91, 1.06]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone | 2018.23 hrs*pg/mL | Standard Deviation 1000.217 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol) | 16532.5 hrs*pg/mL | Standard Deviation 4351.58 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine | 269743 hrs*pg/mL | Standard Deviation 77664.5 |
| EMBEDA | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine | 263270 hrs*pg/mL | Standard Deviation 76706 |
Comparison: Natural log transformed AUC (0-8) was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.905790% CI: [0.94, 1.08]Mixed Models Analysis
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone | 2577.19 hrs*pg/mL | Standard Deviation 1228.398 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol)
AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol) | 26634.5 hrs*pg/mL | Standard Deviation 6167.97 |
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours
Bad effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 2.1 hrs*mm | Standard Deviation 7.82 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 28.4 hrs*mm | Standard Deviation 56.67 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 110.3 hrs*mm | Standard Deviation 116.6 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-112.9, -52.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.07895% CI: [-3.1, 56.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [79.6, 139.8]Mixed Models Analysis
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour
Bad effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.3 hrs*mm | Standard Deviation 0.92 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.6 hrs*mm | Standard Deviation 1.24 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 1.5 hrs*mm | Standard Deviation 3.7 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.045395% CI: [-2, 0]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.563795% CI: [-0.7, 1.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.01195% CI: [0.3, 2.3]Mixed Models Analysis
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours
Bad effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 3.6 hrs*mm | Standard Deviation 13.62 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 36.8 hrs*mm | Standard Deviation 76.5 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 147.2 hrs*mm | Standard Deviation 157.74 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-153.7, -70.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.108995% CI: [-7.8, 75.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [104.1, 187.5]Mixed Models Analysis
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours
Bad effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 0.5 hrs*mm | Standard Deviation 1.65 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 2.6 hrs*mm | Standard Deviation 4.4 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 7.4 hrs*mm | Standard Deviation 12.5 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.004195% CI: [-8.2, -1.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.217895% CI: [-1.2, 5.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [3.7, 10.3]Mixed Models Analysis
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours
Bad effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 0.9 hrs*mm | Standard Deviation 3.2 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 7.7 hrs*mm | Standard Deviation 13.27 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 27.1 hrs*mm | Standard Deviation 36.06 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000195% CI: [-28.8, -9.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.15195% CI: [-2.6, 16.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [16.8, 35.7]Mixed Models Analysis
Secondary
Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours
Bad effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 1.6 hrs*mm | Standard Deviation 5.84 |
| EMBEDA | Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 19.7 hrs*mm | Standard Deviation 37.56 |
| Morphine | Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 74.6 hrs*mm | Standard Deviation 80.92 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-75.9, -34.4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.079695% CI: [-2.2, 39.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [52.9, 94.4]Mixed Models Analysis
Secondary
Bad Effects: Peak Effect (Emax)
Bad effects 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). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Peak Effect (Emax) | 0.6 mm | Standard Deviation 1.6 |
| EMBEDA | Bad Effects: Peak Effect (Emax) | 6.6 mm | Standard Deviation 10.3 |
| Morphine | Bad Effects: Peak Effect (Emax) | 20.1 mm | Standard Deviation 18.98 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-18.8, -8.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.021595% CI: [0.9, 11.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [14.6, 24.8]Mixed Models Analysis
Secondary
Bad Effects: Time to Maximum (Peak) Effect (TEmax)
Bad effects 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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bad Effects: Time to Maximum (Peak) Effect (TEmax) | 0.9 hrs | Standard Deviation 1.6 |
| EMBEDA | Bad Effects: Time to Maximum (Peak) Effect (TEmax) | 2.2 hrs | Standard Deviation 2.38 |
| Morphine | Bad Effects: Time to Maximum (Peak) Effect (TEmax) | 4.5 hrs | Standard Deviation 3.56 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000795% CI: [-3.6, -1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.045595% CI: [0, 2.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [2.3, 4.9]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours
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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours | 2.4 hrs*mm | Standard Deviation 8.68 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours | 27.4 hrs*mm | Standard Deviation 66.65 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours | 71.4 hrs*mm | Standard Deviation 111.82 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.005195% CI: [-73.1, -13.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.094195% CI: [-4.4, 55]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [38.8, 98.4]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour | 0.4 hrs*mm | Standard Deviation 1.28 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour | 0.9 hrs*mm | Standard Deviation 2.41 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour | 3.0 hrs*mm | Standard Deviation 5.73 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.006295% CI: [-3.7, -0.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.499895% CI: [-1, 2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000895% CI: [1.1, 4.2]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours
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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours | 4.0 hrs*mm | Standard Deviation 14.73 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours | 36.0 hrs*mm | Standard Deviation 82.99 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours | 85.5 hrs*mm | Standard Deviation 135.09 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.008395% CI: [-85, -13.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.076695% CI: [-3.5, 68.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [45.4, 117.3]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours
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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours | 0.6 hrs*mm | Standard Deviation 1.7 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours | 2.8 hrs*mm | Standard Deviation 6.26 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours | 9.9 hrs*mm | Standard Deviation 15.14 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000995% CI: [-11.1, -3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.269395% CI: [-1.8, 6.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [5.3, 13.3]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours
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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours | 1.0 hrs*mm | Standard Deviation 2.93 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours | 9.5 hrs*mm | Standard Deviation 21.81 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours | 26.1 hrs*mm | Standard Deviation 41.05 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.004295% CI: [-27.2, -5.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.113995% CI: [-2.2, 19.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [14.1, 35.9]Mixed Models Analysis
Secondary
Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours
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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours | 1.7 hrs*mm | Standard Deviation 5.93 |
| EMBEDA | Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours | 20.9 hrs*mm | Standard Deviation 51.17 |
| Morphine | Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours | 56.7 hrs*mm | Standard Deviation 87 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.003995% CI: [-58.5, -11.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.102695% CI: [-4, 42.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [31, 77.8]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Peak Effect (Emax) | 0.7 mm | Standard Deviation 2.45 |
| EMBEDA | Dizzy: Peak Effect (Emax) | 5.5 mm | Standard Deviation 11.18 |
| Morphine | Dizzy: Peak Effect (Emax) | 13.7 mm | Standard Deviation 17.66 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.001895% CI: [-12.9, -3.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.052795% CI: [-0.1, 9.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [7.9, 17.7]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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 0.5 hrs | Standard Deviation 0.09 |
| EMBEDA | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 2.0 hrs | Standard Deviation 2.57 |
| Morphine | Dizzy: Time to Maximum (Peak) Effect (TEmax) | 2.4 hrs | Standard Deviation 2.6 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.398695% CI: [-1.4, 0.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.002395% CI: [0.6, 2.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000295% CI: [1, 2.9]Mixed Models Analysis
Secondary
Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours
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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours | 591.0 hrs*mm | Standard Deviation 20.36 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours | 658.2 hrs*mm | Standard Deviation 81.77 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours | 732.9 hrs*mm | Standard Deviation 122.81 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000195% CI: [-112.8, -39.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000695% CI: [29.8, 103.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [105.7, 179.3]Mixed Models Analysis
Secondary
Drug Liking: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour | 37.8 hrs*mm | Standard Deviation 1.82 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour | 43.1 hrs*mm | Standard Deviation 6.11 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour | 51.8 hrs*mm | Standard Deviation 10.12 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-11.8, -6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000695% CI: [2.3, 8.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [11.2, 17]Mixed Models Analysis
Secondary
Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours
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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours | 1192.1 hrs*mm | Standard Deviation 29.73 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours | 1263.0 hrs*mm | Standard Deviation 101.88 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours | 1348.2 hrs*mm | Standard Deviation 174.53 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.001195% CI: [-136.5, -35.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.007195% CI: [19.7, 120]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [105.7, 206.3]Mixed Models Analysis
Secondary
Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours
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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours | 188.6 hrs*mm | Standard Deviation 7.56 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours | 217.9 hrs*mm | Standard Deviation 24.72 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours | 265.6 hrs*mm | Standard Deviation 44.44 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-62, -35.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [15.8, 42.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [64.5, 91]Mixed Models Analysis
Secondary
Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours
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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours | 390.3 hrs*mm | Standard Deviation 15.19 |
| EMBEDA | Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours | 447.3 hrs*mm | Standard Deviation 60.82 |
| Morphine | Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours | 514.4 hrs*mm | Standard Deviation 87.1 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-95, -42.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [30.1, 82.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [98.7, 151.5]Mixed Models Analysis
Secondary
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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 5.8 hrs | Standard Deviation 6.83 |
| EMBEDA | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 4.8 hrs | Standard Deviation 5.74 |
| Morphine | Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 2.7 hrs | Standard Deviation 2.63 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.125495% CI: [-0.6, 4.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.459295% CI: [-3.6, 1.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.025195% CI: [-5.6, -0.4]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours
Feel sick 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours | 2.3 hrs*mm | Standard Deviation 8.53 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours | 22.5 hrs*mm | Standard Deviation 54.79 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours | 80.9 hrs*mm | Standard Deviation 113.22 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-88.5, -31.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.155695% CI: [-8, 48.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [52, 108.9]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour
Feel sick 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour | 0.3 hrs*mm | Standard Deviation 1.09 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour | 0.3 hrs*mm | Standard Deviation 0.86 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour | 1.0 hrs*mm | Standard Deviation 3.5 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.1195% CI: [-1.7, 0.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.942195% CI: [-1, 0.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.126695% CI: [-0.2, 1.7]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours
Feel sick 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours | 3.9 hrs*mm | Standard Deviation 14.72 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours | 31.1 hrs*mm | Standard Deviation 73.35 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours | 112.8 hrs*mm | Standard Deviation 160.44 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000195% CI: [-124.8, -43.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.182695% CI: [-13.3, 68.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [70.6, 152.2]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours
Feel sick 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours | 0.6 hrs*mm | Standard Deviation 1.75 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours | 1.7 hrs*mm | Standard Deviation 4.25 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours | 4.2 hrs*mm | Standard Deviation 10.19 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.072395% CI: [-5.3, 0.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.451595% CI: [-1.7, 3.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.012195% CI: [0.8, 6.4]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours
Feel sick 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours | 1.0 hrs*mm | Standard Deviation 3.22 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours | 5.2 hrs*mm | Standard Deviation 12.28 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours | 16.1 hrs*mm | Standard Deviation 28.88 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.005995% CI: [-18.7, -3.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.2895% CI: [-3.5, 11.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000295% CI: [7.5, 22.8]Mixed Models Analysis
Secondary
Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours
Feel sick 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours | 1.7 hrs*mm | Standard Deviation 6.27 |
| EMBEDA | Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours | 14.8 hrs*mm | Standard Deviation 35.83 |
| Morphine | Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours | 50.7 hrs*mm | Standard Deviation 72.35 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000195% CI: [-54.8, -18.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.148895% CI: [-4.8, 31.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [31.8, 67.9]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Peak Effect (Emax) | 0.7 mm | Standard Deviation 1.96 |
| EMBEDA | Feel Sick: Peak Effect (Emax) | 4.9 mm | Standard Deviation 11.06 |
| Morphine | Feel Sick: Peak Effect (Emax) | 16.4 mm | Standard Deviation 17.38 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-16.4, -7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.081195% CI: [-0.5, 8.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [11.1, 20.6]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 0.9 hrs | Standard Deviation 2 |
| EMBEDA | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 1.8 hrs | Standard Deviation 2.77 |
| Morphine | Feel Sick: Time to Maximum (Peak) Effect (TEmax) | 4.3 hrs | Standard Deviation 3.45 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000795% CI: [-3.8, -1.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.163195% CI: [-0.4, 2.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [2.1, 4.8]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours
Good effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 7.8 hrs*mm | Standard Deviation 28.24 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 174.6 hrs*mm | Standard Deviation 153.23 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours | 417.4 hrs*mm | Standard Deviation 158.39 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-302, -187.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [109.5, 223.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [354.3, 468.6]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour
Good effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 0.8 hrs*mm | Standard Deviation 2.47 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 12.2 hrs*mm | Standard Deviation 13.74 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour | 27.2 hrs*mm | Standard Deviation 17.64 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-20.3, -10.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [6.3, 16.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [21.5, 31.5]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours
Good effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 10.2 hrs*mm | Standard Deviation 34.73 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 196.0 hrs*mm | Standard Deviation 176.48 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours | 503.8 hrs*mm | Standard Deviation 223.88 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-384.5, -235.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [110.8, 259.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [420.6, 569.7]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours
Good effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 1.8 hrs*mm | Standard Deviation 6.69 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 30.4 hrs*mm | Standard Deviation 29.84 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours | 77.4 hrs*mm | Standard Deviation 38.39 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-59.5, -35.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [16.5, 40.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [64.2, 87.8]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours
Good effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 3.1 hrs*mm | Standard Deviation 12.35 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 70.5 hrs*mm | Standard Deviation 58.34 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours | 178.5 hrs*mm | Standard Deviation 73.28 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-132.9, -85.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [43.5, 90.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [152.6, 199.9]Mixed Models Analysis
Secondary
Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours
Good effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 6.2 hrs*mm | Standard Deviation 22.44 |
| EMBEDA | Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 141.2 hrs*mm | Standard Deviation 120.31 |
| Morphine | Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours | 330.0 hrs*mm | Standard Deviation 122.85 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-234.2, -147.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [91.5, 178]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [282.1, 368.9]Mixed Models Analysis
Secondary
Good Effects: Peak Effect (Emax)
Good effects 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). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Peak Effect (Emax) | 1.8 mm | Standard Deviation 5.38 |
| EMBEDA | Good Effects: Peak Effect (Emax) | 32.6 mm | Standard Deviation 23.74 |
| Morphine | Good Effects: Peak Effect (Emax) | 63.0 mm | Standard Deviation 20.71 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-38.7, -22.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [22.6, 39]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [53.1, 69.5]Mixed Models Analysis
Secondary
Good Effects: Time to Maximum (Peak) Effect (TEmax)
Good effects 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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Good Effects: Time to Maximum (Peak) Effect (TEmax) | 0.7 hrs | Standard Deviation 0.99 |
| EMBEDA | Good Effects: Time to Maximum (Peak) Effect (TEmax) | 2.5 hrs | Standard Deviation 2.13 |
| Morphine | Good Effects: Time to Maximum (Peak) Effect (TEmax) | 2.6 hrs | Standard Deviation 2.47 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.867195% CI: [-1, 0.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000195% CI: [0.9, 2.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1, 2.8]Mixed Models Analysis
Secondary
High: Area Under Effect Curve (AUE) From 0-12 Hours
High 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-12 Hours | 8.1 hrs*mm | Standard Deviation 28.8 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-12 Hours | 160.7 hrs*mm | Standard Deviation 129.72 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-12 Hours | 412.3 hrs*mm | Standard Deviation 142.08 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-301.5, -204.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [103.5, 200.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [356.4, 453.3]Mixed Models Analysis
Secondary
High: Area Under Effect Curve (AUE) From 0-1 Hour
High 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-1 Hour | 0.9 hrs*mm | Standard Deviation 2.87 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-1 Hour | 10.3 hrs*mm | Standard Deviation 12.26 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-1 Hour | 25.5 hrs*mm | Standard Deviation 16.26 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-19.9, -11]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [4.8, 13.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [20.3, 29.1]Mixed Models Analysis
Secondary
High: Area Under Effect Curve (AUE) From 0-24 Hours
High 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-24 Hours | 10.7 hrs*mm | Standard Deviation 35.41 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-24 Hours | 180.3 hrs*mm | Standard Deviation 149.07 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-24 Hours | 485.4 hrs*mm | Standard Deviation 204.51 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-370.9, -242.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [104.7, 232.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [411.3, 539.6]Mixed Models Analysis
Secondary
High: Area Under Effect Curve (AUE) From 0-4 Hours
High 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-4 Hours | 3.4 hrs*mm | Standard Deviation 13.28 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-4 Hours | 63.6 hrs*mm | Standard Deviation 53.04 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-4 Hours | 178.9 hrs*mm | Standard Deviation 64.56 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-136.5, -95.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [39.3, 80.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [155.4, 196.2]Mixed Models Analysis
Secondary
High: Area Under Effect Curve (AUE) From 0-8 Hours
High 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Area Under Effect Curve (AUE) From 0-8 Hours | 6.5 hrs*mm | Standard Deviation 23.15 |
| EMBEDA | High: Area Under Effect Curve (AUE) From 0-8 Hours | 129.5 hrs*mm | Standard Deviation 101.43 |
| Morphine | High: Area Under Effect Curve (AUE) From 0-8 Hours | 330.5 hrs*mm | Standard Deviation 109.02 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-239, -165.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [85.7, 159.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [287.7, 361.5]Mixed Models Analysis
Secondary
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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High: Time to Maximum (Peak) Effect (TEmax) | 0.8 hrs | Standard Deviation 0.99 |
| EMBEDA | High: Time to Maximum (Peak) Effect (TEmax) | 2.7 hrs | Standard Deviation 1.94 |
| Morphine | High: Time to Maximum (Peak) Effect (TEmax) | 2.5 hrs | Standard Deviation 1.94 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.560795% CI: [-0.6, 1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1.2, 2.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1, 2.6]Mixed Models Analysis
Secondary
Maximum Observed Plasma Concentration (Cmax) of Morphine
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Morphine | 79308.6 picogram/milliliter (pg/mL) | Standard Deviation 31555.86 |
| EMBEDA | Maximum Observed Plasma Concentration (Cmax) of Morphine | 103621 picogram/milliliter (pg/mL) | Standard Deviation 34005.3 |
Comparison: Natural log transformed Cmax was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000190% CI: [0.68, 0.83]Mixed Models Analysis
Secondary
Maximum Observed Plasma Concentration (Cmax) of Naltrexone
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Naltrexone | 978.83 pg/mL | Standard Deviation 713.748 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol) | 6226.3 pg/mL | Standard Deviation 2158.29 |
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-12 Hours
Nausea 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-12 Hours | 2.2 hrs*mm | Standard Deviation 7.42 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-12 Hours | 25.2 hrs*mm | Standard Deviation 61.13 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-12 Hours | 76.9 hrs*mm | Standard Deviation 119.64 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000695% CI: [-83.2, -24]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.120795% CI: [-6.3, 52.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [47.3, 106.4]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-1 Hour
Nausea 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: Pre-dose, 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour | 0.4 hrs*mm | Standard Deviation 1.28 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour | 0.5 hrs*mm | Standard Deviation 1.16 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-1 Hour | 0.8 hrs*mm | Standard Deviation 2.25 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.374995% CI: [-0.9, 0.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.793995% CI: [-0.5, 0.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.252495% CI: [-0.3, 1]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-24 Hours
Nausea 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-24 Hours | 3.8 hrs*mm | Standard Deviation 13.69 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-24 Hours | 35.3 hrs*mm | Standard Deviation 76.53 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-24 Hours | 108.3 hrs*mm | Standard Deviation 171.22 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000895% CI: [-118.6, -33]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.14195% CI: [-10.8, 74.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [64.9, 150.5]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-2 Hours
Nausea 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-2 Hours | 0.7 hrs*mm | Standard Deviation 1.73 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-2 Hours | 2.1 hrs*mm | Standard Deviation 4.12 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-2 Hours | 3.7 hrs*mm | Standard Deviation 8.14 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.121195% CI: [-3.8, 0.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.199795% CI: [-0.7, 3.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.005795% CI: [0.9, 5.2]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-4 Hours
Nausea 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-4 Hours | 1.0 hrs*mm | Standard Deviation 2.78 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-4 Hours | 5.5 hrs*mm | Standard Deviation 11.3 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-4 Hours | 15.3 hrs*mm | Standard Deviation 26.61 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.005795% CI: [-16.7, -3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.191895% CI: [-2.3, 11.4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [7.5, 21.2]Mixed Models Analysis
Secondary
Nausea: Area Under Effect Curve (AUE) From 0-8 Hours
Nausea 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Area Under Effect Curve (AUE) From 0-8 Hours | 1.6 hrs*mm | Standard Deviation 5.17 |
| EMBEDA | Nausea: Area Under Effect Curve (AUE) From 0-8 Hours | 16.5 hrs*mm | Standard Deviation 39.86 |
| Morphine | Nausea: Area Under Effect Curve (AUE) From 0-8 Hours | 47.1 hrs*mm | Standard Deviation 75.02 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.001395% CI: [-50.2, -12.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.113695% CI: [-3.7, 33.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [27.8, 65.1]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Peak Effect (Emax) | 0.8 mm | Standard Deviation 2.41 |
| EMBEDA | Nausea: Peak Effect (Emax) | 5.2 mm | Standard Deviation 10.41 |
| Morphine | Nausea: Peak Effect (Emax) | 14.9 mm | Standard Deviation 17.14 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-14.4, -5.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.052995% CI: [-0.1, 8.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [9.9, 18.7]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nausea: Time to Maximum (Peak) Effect (TEmax) | 1.4 hrs | Standard Deviation 4.17 |
| EMBEDA | Nausea: Time to Maximum (Peak) Effect (TEmax) | 2.5 hrs | Standard Deviation 4.69 |
| Morphine | Nausea: Time to Maximum (Peak) Effect (TEmax) | 4.3 hrs | Standard Deviation 3.52 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.080695% CI: [-3.8, 0.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.276995% CI: [-0.9, 3.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.005695% CI: [0.9, 5]Mixed Models Analysis
Secondary
Overall Drug Liking Effect at 24 Hours
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 carryover 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: 24 hrs post dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Drug Liking Effect at 24 Hours | 50.6 mm | Standard Deviation 3.06 |
| EMBEDA | Overall Drug Liking Effect at 24 Hours | 58.8 mm | Standard Deviation 17.68 |
| Morphine | Overall Drug Liking Effect at 24 Hours | 69.8 mm | Standard Deviation 20.23 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.002995% CI: [-18, -4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.028695% CI: [1, 15]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [12, 27]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours | 0.7 hrs*mm | Standard Deviation 4.78 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours | -20.8 hrs*mm | Standard Deviation 6.8 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours | -32.6 hrs*mm | Standard Deviation 7.95 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [8.7, 14.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-24.5, -18.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-36.2, -30.2]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1).
Time frame: Pre-dose, 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour | 0.0 hrs*mm | Standard Deviation 0.4 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour | -0.5 hrs*mm | Standard Deviation 0.38 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour | -1.2 hrs*mm | Standard Deviation 0.6 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [0.5, 0.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-0.8, -0.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-1.5, -1]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours | 3.5 hrs*mm | Standard Deviation 9.19 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours | -34.2 hrs*mm | Standard Deviation 13.96 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours | -51.8 hrs*mm | Standard Deviation 15.26 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [11.6, 23.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-43.6, -31.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-61.1, -49.3]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours | 0.0 hrs*mm | Standard Deviation 0.87 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours | -1.7 hrs*mm | Standard Deviation 1.07 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours | -4.1 hrs*mm | Standard Deviation 1.31 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1.9, 2.9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-2.2, -1.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-4.6, -3.6]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours | -0.1 hrs*mm | Standard Deviation 1.67 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours | -5.4 hrs*mm | Standard Deviation 2.29 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours | -10.3 hrs*mm | Standard Deviation 2.58 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [3.9, 5.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-6.3, -4.3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-11.1, -9.2]Mixed Models Analysis
Secondary
Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours | 0.0 hrs*mm | Standard Deviation 3.25 |
| EMBEDA | Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours | -13.8 hrs*mm | Standard Deviation 4.36 |
| Morphine | Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours | -22.5 hrs*mm | Standard Deviation 5.35 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [6.6, 10.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-15.9, -11.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-24.5, -20.4]Mixed Models Analysis
Secondary
Pupillometry: Peak Effect (Emax)
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. Emax = Smallest post-dose pupil size.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Peak Effect (Emax) | 5.6 mm | Standard Deviation 0.76 |
| EMBEDA | Pupillometry: Peak Effect (Emax) | 3.9 mm | Standard Deviation 0.71 |
| Morphine | Pupillometry: Peak Effect (Emax) | 2.8 mm | Standard Deviation 0.74 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [0.8, 1.4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-2.1, -1.5]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-3.2, -2.6]Mixed Models Analysis
Secondary
Pupillometry: Time to Maximum (Peak) Effect (TEmax)
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. TEmax = Time to smallest post-dose pupil size.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 4.8 hrs | Standard Deviation 6.83 |
| EMBEDA | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 5.6 hrs | Standard Deviation 2.26 |
| Morphine | Pupillometry: Time to Maximum (Peak) Effect (TEmax) | 3.2 hrs | Standard Deviation 1.64 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.026295% CI: [0.3, 4.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.41895% CI: [-1.3, 3]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.147995% CI: [-3.7, 0.6]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours
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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours | 5.3 hrs*mm | Standard Deviation 13.05 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours | 138.5 hrs*mm | Standard Deviation 140.93 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours | 287.5 hrs*mm | Standard Deviation 196.29 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-205.1, -89.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [76.5, 191.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [223.7, 339.2]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr(0-1).
Time frame: 0.5 and 1 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour | 0.4 hrs*mm | Standard Deviation 1.3 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour | 2.4 hrs*mm | Standard Deviation 6.57 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour | 3.6 hrs*mm | Standard Deviation 5.13 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.211795% CI: [-3.1, 0.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.034595% CI: [0.2, 4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.001195% CI: [1.4, 5.2]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours
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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours | 7.6 hrs*mm | Standard Deviation 21.06 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours | 175.5 hrs*mm | Standard Deviation 175.65 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours | 378.7 hrs*mm | Standard Deviation 267.76 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-279.3, -123.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [91.5, 246.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [292.7, 448.4]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours
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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2).
Time frame: 0.5, 1, 1.5 and 2 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours | 0.7 hrs*mm | Standard Deviation 1.91 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours | 9.1 hrs*mm | Standard Deviation 12.63 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours | 21.3 hrs*mm | Standard Deviation 21.28 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000295% CI: [-18.4, -6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.008195% CI: [2.3, 14.6]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [14.4, 26.8]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours
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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4).
Time frame: 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours | 1.7 hrs*mm | Standard Deviation 4.31 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours | 35.9 hrs*mm | Standard Deviation 38.78 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours | 74.2 hrs*mm | Standard Deviation 61.41 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-55.6, -20.8]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.000295% CI: [17, 51.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [55.2, 90]Mixed Models Analysis
Secondary
Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours
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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours | 4.2 hrs*mm | Standard Deviation 10.15 |
| EMBEDA | Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours | 97.6 hrs*mm | Standard Deviation 103.13 |
| Morphine | Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours | 199.2 hrs*mm | Standard Deviation 141.96 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-142.2, -58.4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [52.1, 135.7]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [152.3, 236.1]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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Peak Effect (Emax) | 1.5 mm | Standard Deviation 3.71 |
| EMBEDA | Sleepy: Peak Effect (Emax) | 27.1 mm | Standard Deviation 22.75 |
| Morphine | Sleepy: Peak Effect (Emax) | 43.9 mm | Standard Deviation 21.93 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [-23.8, -9]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [18.3, 33.1]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [34.7, 49.5]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: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 1.1 hrs | Standard Deviation 2.2 |
| EMBEDA | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 4.0 hrs | Standard Deviation 2.94 |
| Morphine | Sleepy: Time to Maximum (Peak) Effect (TEmax) | 5.3 hrs | Standard Deviation 2.81 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.025395% CI: [-2.6, -0.2]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [1.6, 4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [3, 5.4]Mixed Models Analysis
Secondary
Take Drug Again Effect at 24 Hours
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).
Time frame: 24 hrs post dose
Population: The evaluable population included all randomized participants who completed all 3 treatment periods of the treatment phase, contributed post-dose PD data from each period and did not have major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Take Drug Again Effect at 24 Hours | 49.8 mm | Standard Deviation 4.41 |
| EMBEDA | Take Drug Again Effect at 24 Hours | 58.0 mm | Standard Deviation 21.9 |
| Morphine | Take Drug Again Effect at 24 Hours | 70.6 mm | Standard Deviation 24.53 |
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.00595% CI: [-22, -4]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.0795% CI: [-1, 17]Mixed Models Analysis
Comparison: LS mean, 95% CI, and unadjusted p-value were calculated using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: <0.000195% CI: [12, 30]Mixed Models Analysis
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine | 0.9 hrs | Standard Deviation 0.48 |
| EMBEDA | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine | 0.7 hrs | Standard Deviation 0.25 |
Comparison: Tmax was analyzed using linear mixed model with fixed effects for sequence, period and treatment, and a random effect for participant nested in sequence.p-value: 0.018190% CI: [0.07, 0.35]Mixed Models Analysis
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone | 0.8 hrs | Standard Deviation 0.32 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose
Population: Safety population included all participants who received at least one dose of study drug in the Treatment Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol) | 1.0 hrs | Standard Deviation 0.61 |