Pain, Nausea, Vomiting
Conditions
Keywords
Pain, Nausea, Vomiting
Brief summary
The purpose of this study is to assess the abuse potential of CL-108 tablets, including the abuse deterrent effects of promethazine, following oral administration, relative to hydrocodone/acetaminophen (APAP) tablets and placebo in non-dependent, recreational opioid users.
Detailed description
The purpose of this study is to assess the abuse potential of CL-108 tablets, including the abuse deterrent effects of promethazine, following oral administration, relative to hydrocodone/acetaminophen (APAP) tablets and placebo in non-dependent, recreational opioid users; to assess the cognitive and behavioral effects of CL-108 tablets following oral administration relative to hydrocodone/APAP tablets and placebo in non-dependent, recreational opioid users; and to assess the safety of orally administered CL-108 tablets relative to hydrocodone/APAP tablets and placebo in non-dependent, recreational opioid users.
Interventions
Sponsors
Charleston Laboratories, Inc
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
* BMI within 18.0 to 33.0 kg/m2, inclusive (minimum weight of 50.0 kg at Screening) * Healthy, as determined by no clinically significant medical history, physical examination findings, 12-lead ECG findings, vital signs measurements, and laboratory results at screening, as judged by the investigator * Current opioid users who had used oral opioids for recreational (non-therapeutic) purposes, at least 10 times in the past year
Exclusion criteria
* Drug or alcohol dependence within the last 12 months (except nicotine) * Subjects who had ever been in treatment for substance use disorders (except smoking cessation * History of presence of any clinically significant cardiac, neurologic, pulmonary, psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, dermatologic, renal, or other major disease at screening, which in the opinion of the investigator, would have jeopardized the safety of the subject or the validity of the study results * History or presence of hypotension, judged to be clinically significant based on investigator judgement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose) | High VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). For VAS assessment, pre-dose (baseline) value was subtracted from each post-dose value prior to calculation of the pharmacodynamic (PD) parameter. Emax is the largest effect score and Emin is the smallest effect score between 0 to 24 hours post-dose. |
| Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose) | Any drug effects VAS measures other subjective effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0 (pre-dose) to 24 hours post-dose. |
| Emax of Drug Liking VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 and 24 hours | Drug liking VAS is the measure of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar (VAS) anchored in the center with a neutral anchor of 'neither like nor dislike' (score of 50 mm), on the left with 'strong disliking' (score of 0 mm) and on the right with 'strong liking' (score of 100 mm). Emax is the largest effect score between 0.5 to 24 hours post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Overall drug liking VAS is the measure of balance of effects that 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 bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = 'strong disliking', 50 mm = 'neither like nor dislike', and 100 mm = 'strong liking'). Emax is the largest effect score and Emin is the smallest effect score between 0 to 8 hours post-dose. |
| Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Take drug again VAS is the measure of balance of effects. It 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 bipolar VAS with score ranging from 0 mm to 100 mm (0 mm = 'definitely not', 50 mm = 'do not care', and 100 mm = 'definitely so'). Emax is the largest effect score and Emin is the smallest effect score between 0 to 8 hours post-dose. |
| Positive Effects: Emax of High VAS in Treatment Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | High VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). For VAS assessment, pre-dose (baseline) value was subtracted from each post-dose value prior to calculation of the pharmacodynamic (PD) parameter. Emax is the largest effect score between 0 to 8 hours. |
| Positive Effects: TA_AUE of High VAS in Treatment Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
| Positive Effects: Emax of Good Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Good drug effects VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hours post-dose. |
| Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
| Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Bad effects VAS measures the negative effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hrs. |
| Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
| Number of Adverse Events in Dose Selection Phase | Up to visit 3 (Follow up) | AE=Adverse Event. SAE=Serious adverse event. TEAE=Treatment-emergent adverse event. |
| Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | Alertness/Drowsiness VAS measures the sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of 'neither drowsy nor alert' (score of 50 mm), on the left with 'very drowsy' (score of 0 mm) and on the right with 'very alert' (score of 100 mm). Alertness/Drowsiness VAS was calculated by subtracting pre-dose (baseline) value from each post-dose value. TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using trapezoidal rule. |
| Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Any drug effects VAS measures other subjective effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hours post-dose. |
| Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
| Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose) | CRT is a computerized 5-choice reaction time test in which the subject must press and hold down a touchscreen button at the bottom of the screen. A yellow spot appeared inside one of 5 yellow circles at the top of the screen. Subjects were to respond to the spot as quickly as they could by letting go of the button and touching the circle where the yellow spot appeared. This was repeated for 30 trials. Lower scores indicate better performance. |
| Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose) | CRT is a computerized 5-choice reaction time test in which the subject must press and hold down a touchscreen button at the bottom of the screen. A yellow spot appeared inside one of 5 yellow circles at the top of the screen. Subjects were to respond to the spot as quickly as they could by letting go of the button and touching the circle where the yellow spot appeared. This was repeated for 30 trials. Lower scores indicate better performance. CRT also measures error scores and response accuracy. Any Errors is a combination of incorrect location errors, inaccurate response errors, no response errors, and premature errors. |
| Pupillometry: Maximum Pupil Constriction (MPC) | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. Pupil diameter was measured using electronic pupillometer. Measurements were collected under mesopic lighting conditions. For each subject, every effort was made to use the same eye for all assessments throughout the study. MPC is calculated as smallest observed pupil diameter - baseline pupil diameter. |
| Pupillometry: TA_AUE of MPC in Treatment Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
| Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose) | Alertness/Drowsiness VAS measures the sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of 'neither drowsy nor alert' (score of 50 mm), on the left with 'very drowsy' (score of 0 mm) and on the right with 'very alert' (score of 100 mm). Alertness/Drowsiness VAS was calculated by subtracting pre-dose (baseline) value from each post-dose value. Emin is the smallest effect score between 0 to 8 hours post-dose. |
| Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | Drug liking VAS is the measure of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar (VAS) anchored in the center with a neutral anchor of 'neither like nor dislike' (score of 50 mm), on the left with 'strong disliking' (score of 0 mm) and on the right with 'strong liking' (score of 100 mm). Emin is the smallest effect score between 0.5 to 8 hours post-dose. |
| Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours | TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule. |
Participant flow
Recruitment details
Total 12 subjects were enrolled and completed the Dose Selection phase. Subjects randomized to the Treatment phase were 40 and all of them received at least 1 dose of study drug, and 37 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Part A (Dose Selection Phase): CL-108 or Placebo Treatment AA: CL-108 15 mg/650 mg/25 mg tablet by mouth
Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
Treatment CC: CL-108 30 mg/1300 mg/50 mg tablet by mouth
Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
Treatment EE: Placebo 0 mg tablet by mouth | 12 |
| Part B (Treatment Phase): CL-108, M366 and Placebo Treatment A (low-dose): CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
Treatment B (high-dose): CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
Treatment C (low-dose): M366 22.5 mg/975 mg tablet by mouth
Treatment D (high-dose): M366 37.5 mg/1625 mg tablet by mouth
Treatment E: Placebo 0 mg tablet by mouth | 40 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B: Qualification Phase | Adverse Event | 0 | 1 |
| Part B: Qualification Phase | Drug Discrimination Failure | 0 | 13 |
| Part B: Qualification Phase | Sponsor Decision | 0 | 4 |
| Part B: Qualification Phase | Withdrawal by Subject | 0 | 3 |
| Part B: Treatment Phase | Adverse Event | 0 | 1 |
| Part B: Treatment Phase | Other | 0 | 1 |
| Part B: Treatment Phase | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part A (Dose Selection Phase): CL-108 or Placebo | Part B (Treatment Phase): CL-108, M366 and Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 40 Participants | 52 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 Participants | 36 Participants | 45 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 34 Participants | 44 Participants |
| Region of Enrollment United States | 12 participants | 40 participants | 52 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 32 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 2 / 2 | 1 / 2 | 2 / 2 | 0 / 4 | 30 / 40 | 34 / 39 | 28 / 38 | 31 / 39 | 14 / 39 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 4 | 0 / 40 | 0 / 39 | 0 / 38 | 0 / 39 | 0 / 39 |
Outcome results
Primary
Emax of Drug Liking VAS in Treatment Phase
Drug liking VAS is the measure of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar (VAS) anchored in the center with a neutral anchor of 'neither like nor dislike' (score of 50 mm), on the left with 'strong disliking' (score of 0 mm) and on the right with 'strong liking' (score of 100 mm). Emax is the largest effect score between 0.5 to 24 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 and 24 hours
Population: Intended to treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Emax of Drug Liking VAS in Treatment Phase | 77.3 units on a scale | Standard Deviation 14.68 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Emax of Drug Liking VAS in Treatment Phase | 81.4 units on a scale | Standard Deviation 13.1 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Emax of Drug Liking VAS in Treatment Phase | 74.4 units on a scale | Standard Deviation 13.75 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Emax of Drug Liking VAS in Treatment Phase | 79.8 units on a scale | Standard Deviation 13.07 |
| Treatment EE: Placebo | Emax of Drug Liking VAS in Treatment Phase | 54.5 units on a scale | Standard Deviation 9.95 |
p-value: <0.0001ANOVA
p-value: <0.0001ANOVA
p-value: 0.2344ANOVA
p-value: 0.4737ANOVA
p-value: <0.0001ANOVA
p-value: <0.0001ANOVA
Primary
Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase
Any drug effects VAS measures other subjective effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0 (pre-dose) to 24 hours post-dose.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose)
Population: Safety population.~Parameters were not calculated for subjects who experienced emesis within the first 3 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 86.0 units on a scale | Standard Deviation 19.8 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 48.5 units on a scale | Standard Deviation 26.16 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 75.0 units on a scale | Standard Deviation 35.36 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 94.0 units on a scale | — |
| Treatment EE: Placebo | Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase | 4.3 units on a scale | Standard Deviation 5.68 |
Primary
Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase
High VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). For VAS assessment, pre-dose (baseline) value was subtracted from each post-dose value prior to calculation of the pharmacodynamic (PD) parameter. Emax is the largest effect score and Emin is the smallest effect score between 0 to 24 hours post-dose.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose)
Population: Safety population.~Parameters were not calculated for subjects who experienced emesis within the first 3 hours post-dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emin | 3.0 units on a scale | Standard Deviation 4.24 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emax | 85.0 units on a scale | Standard Deviation 21.21 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emin | 23.5 units on a scale | Standard Deviation 3.54 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emax | 42.0 units on a scale | Standard Deviation 21.21 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emax | 75.5 units on a scale | Standard Deviation 34.65 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emin | 42.0 units on a scale | Standard Deviation 11.31 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emax | 94.0 units on a scale | — |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emin | 7.0 units on a scale | — |
| Treatment EE: Placebo | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emin | 60.8 units on a scale | Standard Deviation 20.84 |
| Treatment EE: Placebo | Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase | Emax | 2.3 units on a scale | Standard Deviation 4.5 |
Secondary
Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase
Overall drug liking VAS is the measure of balance of effects that 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 bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = 'strong disliking', 50 mm = 'neither like nor dislike', and 100 mm = 'strong liking'). Emax is the largest effect score and Emin is the smallest effect score between 0 to 8 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emax | 70.4 units on a scale | Standard Deviation 17.77 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emin | 61.2 units on a scale | Standard Deviation 17.07 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emin | 66.7 units on a scale | Standard Deviation 19.96 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emax | 75.8 units on a scale | Standard Deviation 17.16 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emax | 65.2 units on a scale | Standard Deviation 17.89 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emin | 57.2 units on a scale | Standard Deviation 18.85 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emax | 71.1 units on a scale | Standard Deviation 16.81 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emin | 59.2 units on a scale | Standard Deviation 18.5 |
| Treatment EE: Placebo | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emin | 48.7 units on a scale | Standard Deviation 9.21 |
| Treatment EE: Placebo | Balance of Effects: Emax and Emin of Overall Drug Liking VAS in Treatment Phase | Emax | 52.2 units on a scale | Standard Deviation 8.74 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.1267ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.1767ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emin: Treatment C (low-dose M366) - Placebop-value: 0.0119ANOVA
Comparison: Emin: Treatment D (high-dose M366) - Placebop-value: 0.0025ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.1679ANOVA
Comparison: Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.0318ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Placebop-value: 0.0002ANOVA
p-value: <0.0001ANOVA
Secondary
Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase
Take drug again VAS is the measure of balance of effects. It 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 bipolar VAS with score ranging from 0 mm to 100 mm (0 mm = 'definitely not', 50 mm = 'do not care', and 100 mm = 'definitely so'). Emax is the largest effect score and Emin is the smallest effect score between 0 to 8 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emax | 74.6 units on a scale | Standard Deviation 18.98 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emin | 66.4 units on a scale | Standard Deviation 19.85 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emin | 69.3 units on a scale | Standard Deviation 21.07 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emax | 75.2 units on a scale | Standard Deviation 18.49 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emin | 60.9 units on a scale | Standard Deviation 21.19 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emax | 68.9 units on a scale | Standard Deviation 19.89 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emin | 61.9 units on a scale | Standard Deviation 20.68 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emax | 71.3 units on a scale | Standard Deviation 20.51 |
| Treatment EE: Placebo | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emax | 51.1 units on a scale | Standard Deviation 12.45 |
| Treatment EE: Placebo | Balance of Effects: Emax and Emin of Take Drug Again VAS in Treatment Phase | Emin | 47.5 units on a scale | Standard Deviation 12.04 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.0858ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.2877ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emin: Treatment C (low-dose M366) - Placebop-value: 0.0009ANOVA
Comparison: Emin: Treatment D (high-dose M366) - Placebop-value: 0.0001ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.113ANOVA
Comparison: Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.0575ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emin: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Balance of Effects: Emin of Drug Liking VAS in Treatment Phase
Drug liking VAS is the measure of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar (VAS) anchored in the center with a neutral anchor of 'neither like nor dislike' (score of 50 mm), on the left with 'strong disliking' (score of 0 mm) and on the right with 'strong liking' (score of 100 mm). Emin is the smallest effect score between 0.5 to 8 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 49.0 units on a scale | Standard Deviation 3.16 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 46.6 units on a scale | Standard Deviation 12.16 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 44.8 units on a scale | Standard Deviation 11.67 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 46.5 units on a scale | Standard Deviation 12.96 |
| Treatment EE: Placebo | Balance of Effects: Emin of Drug Liking VAS in Treatment Phase | 47.1 units on a scale | Standard Deviation 11.42 |
Secondary
Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 12.071 units on a scale | Standard Deviation 10.4456 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 13.772 units on a scale | Standard Deviation 10.6773 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 9.773 units on a scale | Standard Deviation 12.4254 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 11.162 units on a scale | Standard Deviation 12.8093 |
| Treatment EE: Placebo | Balance of Effects: Time-averaged Area Under the Effect Curve (TA_AUE) of Drug Liking VAS in Treatment Phase | 1.183 units on a scale | Standard Deviation 5.0571 |
Secondary
Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase
CRT is a computerized 5-choice reaction time test in which the subject must press and hold down a touchscreen button at the bottom of the screen. A yellow spot appeared inside one of 5 yellow circles at the top of the screen. Subjects were to respond to the spot as quickly as they could by letting go of the button and touching the circle where the yellow spot appeared. This was repeated for 30 trials. Lower scores indicate better performance. CRT also measures error scores and response accuracy. Any Errors is a combination of incorrect location errors, inaccurate response errors, no response errors, and premature errors.
Time frame: 0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose)
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 8 hrs post-dose | 0.2 Error per msec | Standard Deviation 1.95 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | Baseline (Predose) | 0.6 Error per msec | Standard Deviation 0.86 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 2 hrs post-dose | 0.4 Error per msec | Standard Deviation 1.48 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 4 hrs post-dose | 0.5 Error per msec | Standard Deviation 1.3 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 24 hrs post-dose | 0.3 Error per msec | Standard Deviation 1.49 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 1 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.29 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | Baseline (Predose) | 0.4 Error per msec | Standard Deviation 0.9 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 8 hrs post-dose | 0.9 Error per msec | Standard Deviation 2.11 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 1 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.28 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 24 hrs post-dose | -0.1 Error per msec | Standard Deviation 0.92 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 2 hrs post-dose | 0.9 Error per msec | Standard Deviation 1.45 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 4 hrs post-dose | 1.4 Error per msec | Standard Deviation 2.15 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 2 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.18 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 1 hrs post-dose | 0.97 Error per msec | Standard Deviation 0.16 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | Baseline (Predose) | 0.5 Error per msec | Standard Deviation 0.87 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 8 hrs post-dose | 0.1 Error per msec | Standard Deviation 0.94 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 24 hrs post-dose | 0.5 Error per msec | Standard Deviation 1.12 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 4 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.26 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | Baseline (Predose) | 0.8 Error per msec | Standard Deviation 1.09 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 1 hrs post-dose | 1.21 Error per msec | Standard Deviation 0.2 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 2 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.33 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 4 hrs post-dose | -0.1 Error per msec | Standard Deviation 1.36 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 8 hrs post-dose | 0.0 Error per msec | Standard Deviation 1.21 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 24 hrs post-dose | -0.1 Error per msec | Standard Deviation 0.91 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 8 hrs post-dose | 0.1 Error per msec | Standard Deviation 0.19 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 2 hrs post-dose | 0.2 Error per msec | Standard Deviation 0.92 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 1 hrs post-dose | 0.70 Error per msec | Standard Deviation 0.12 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | Baseline (Predose) | 0.90 Error per msec | Standard Deviation 0.15 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 4 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.1 |
| Treatment EE: Placebo | Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase | 24 hrs post-dose | 0.1 Error per msec | Standard Deviation 1.04 |
Secondary
Negative Effects: Emax of Bad Effects VAS in Treatment Phase
Bad effects VAS measures the negative effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hrs.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 14.8 units on a scale | Standard Deviation 21.89 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 30.1 units on a scale | Standard Deviation 29.35 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 20.1 units on a scale | Standard Deviation 20.61 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 36.1 units on a scale | Standard Deviation 30.39 |
| Treatment EE: Placebo | Negative Effects: Emax of Bad Effects VAS in Treatment Phase | 2.4 units on a scale | Standard Deviation 9.68 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.2223ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.1638ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: 0.0041ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.001ANOVA
Secondary
Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 5.487 units on a scale | Standard Deviation 10.5253 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 12.535 units on a scale | Standard Deviation 16.0605 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 7.171 units on a scale | Standard Deviation 9.8243 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 13.830 units on a scale | Standard Deviation 14.9453 |
| Treatment EE: Placebo | Negative Effects: TA_AUE of Bad Effects VAS in Treatment Phase | 0.217 units on a scale | Standard Deviation 0.9084 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: 0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.2706ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.5507ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: 0.0047ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Number of Adverse Events in Dose Selection Phase
AE=Adverse Event. SAE=Serious adverse event. TEAE=Treatment-emergent adverse event.
Time frame: Up to visit 3 (Follow up)
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Number of Adverse Events in Dose Selection Phase | Total number of AEs | 16 Event |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Number of Adverse Events in Dose Selection Phase | Total Number of TEAEs | 14 Event |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Number of Adverse Events in Dose Selection Phase | Number of SAEs | 0 Event |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Number of Adverse Events in Dose Selection Phase | Number of AEs leading to Discontinuation | 0 Event |
Secondary
Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase
CRT is a computerized 5-choice reaction time test in which the subject must press and hold down a touchscreen button at the bottom of the screen. A yellow spot appeared inside one of 5 yellow circles at the top of the screen. Subjects were to respond to the spot as quickly as they could by letting go of the button and touching the circle where the yellow spot appeared. This was repeated for 30 trials. Lower scores indicate better performance.
Time frame: 0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose)
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 4 hrs post-dose | 23.4 msec | Standard Deviation 155.96 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 1 hrs post-dose | -7.0 msec | Standard Deviation 104.21 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | Baseline (Predose) | 74.0 msec | Standard Deviation 103.15 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 24 hrs post-dose | -20.6 msec | Standard Deviation 103.86 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 8 hrs post-dose | -4.6 msec | Standard Deviation 104.99 |
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 2 hrs post-dose | 21.7 msec | Standard Deviation 160.21 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | Baseline (Predose) | 51.9 msec | Standard Deviation 22.52 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 1 hrs post-dose | 9.8 msec | Standard Deviation 23.32 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 4 hrs post-dose | 38.3 msec | Standard Deviation 74.27 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 2 hrs post-dose | 45.5 msec | Standard Deviation 81.23 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 8 hrs post-dose | 29.0 msec | Standard Deviation 56.17 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 24 hrs post-dose | 4.9 msec | Standard Deviation 35.28 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | Baseline (Predose) | 51.2 msec | Standard Deviation 16.83 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 2 hrs post-dose | 24.8 msec | Standard Deviation 93.63 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 4 hrs post-dose | 11.0 msec | Standard Deviation 32.97 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 8 hrs post-dose | 4.9 msec | Standard Deviation 30.03 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 1 hrs post-dose | 8.4 msec | Standard Deviation 24.48 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 24 hrs post-dose | 16.7 msec | Standard Deviation 70.86 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 8 hrs post-dose | 9.0 msec | Standard Deviation 45.69 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | Baseline (Predose) | 56.8 msec | Standard Deviation 28.83 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 1 hrs post-dose | 11.1 msec | Standard Deviation 46.97 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 24 hrs post-dose | 6.3 msec | Standard Deviation 46.15 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 2 hrs post-dose | 21.2 msec | Standard Deviation 55.12 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 4 hrs post-dose | 7.9 msec | Standard Deviation 27.71 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 2 hrs post-dose | 8.8 msec | Standard Deviation 27.77 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 4 hrs post-dose | 5.1 msec | Standard Deviation 20.1 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 1 hrs post-dose | 3.9 msec | Standard Deviation 34.65 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 24 hrs post-dose | 4.1 msec | Standard Deviation 29.93 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | 8 hrs post-dose | 4.9 msec | Standard Deviation 30.57 |
| Treatment EE: Placebo | Objective Measures: Change From Baseline in Choice Reaction Time (CRT) in Treatment Phase | Baseline (Predose) | 55.0 msec | Standard Deviation 19.48 |
Secondary
Positive Effects: Emax of Good Effects VAS in Treatment Phase
Good drug effects VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Positive Effects: Emax of Good Effects VAS in Treatment Phase | 6.3 units on a scale | Standard Deviation 15.06 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Positive Effects: Emax of Good Effects VAS in Treatment Phase | 59.3 units on a scale | Standard Deviation 29.42 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Positive Effects: Emax of Good Effects VAS in Treatment Phase | 68.3 units on a scale | Standard Deviation 25.99 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Positive Effects: Emax of Good Effects VAS in Treatment Phase | 52.5 units on a scale | Standard Deviation 29.35 |
| Treatment EE: Placebo | Positive Effects: Emax of Good Effects VAS in Treatment Phase | 62.2 units on a scale | Standard Deviation 23.24 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.1839ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.1751ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Positive Effects: Emax of High VAS in Treatment Phase
High VAS measures the positive effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). For VAS assessment, pre-dose (baseline) value was subtracted from each post-dose value prior to calculation of the pharmacodynamic (PD) parameter. Emax is the largest effect score between 0 to 8 hours.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Positive Effects: Emax of High VAS in Treatment Phase | 58.9 units on a scale | Standard Deviation 29.05 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Positive Effects: Emax of High VAS in Treatment Phase | 71.8 units on a scale | Standard Deviation 26.07 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Positive Effects: Emax of High VAS in Treatment Phase | 54.6 units on a scale | Standard Deviation 28.41 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Positive Effects: Emax of High VAS in Treatment Phase | 67.5 units on a scale | Standard Deviation 22.76 |
| Treatment EE: Placebo | Positive Effects: Emax of High VAS in Treatment Phase | 5.4 units on a scale | Standard Deviation 12.92 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.4025ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.3184ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 28.108 units on a scale | Standard Deviation 22.0759 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 34.894 units on a scale | Standard Deviation 20.5885 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 25.541 units on a scale | Standard Deviation 23.1053 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 29.327 units on a scale | Standard Deviation 19.7001 |
| Treatment EE: Placebo | Positive Effects: TA_AUE of Good Effects VAS in Treatment Phase | 1.140 units on a scale | Standard Deviation 2.9074 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.4013ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.0736ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Positive Effects: TA_AUE of High VAS in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Positive Effects: TA_AUE of High VAS in Treatment Phase | 1.055 units on a scale | Standard Deviation 2.8942 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Positive Effects: TA_AUE of High VAS in Treatment Phase | 27.850 units on a scale | Standard Deviation 21.6226 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Positive Effects: TA_AUE of High VAS in Treatment Phase | 36.363 units on a scale | Standard Deviation 21.0716 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Positive Effects: TA_AUE of High VAS in Treatment Phase | 24.500 units on a scale | Standard Deviation 20.8024 |
| Treatment EE: Placebo | Positive Effects: TA_AUE of High VAS in Treatment Phase | 32.050 units on a scale | Standard Deviation 20.7004 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.2628ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.2262ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Pupillometry: Maximum Pupil Constriction (MPC)
Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. Pupil diameter was measured using electronic pupillometer. Measurements were collected under mesopic lighting conditions. For each subject, every effort was made to use the same eye for all assessments throughout the study. MPC is calculated as smallest observed pupil diameter - baseline pupil diameter.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Pupillometry: Maximum Pupil Constriction (MPC) | 2.51 mm | Standard Deviation 0.852 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Pupillometry: Maximum Pupil Constriction (MPC) | 3.15 mm | Standard Deviation 0.783 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Pupillometry: Maximum Pupil Constriction (MPC) | 2.34 mm | Standard Deviation 0.852 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Pupillometry: Maximum Pupil Constriction (MPC) | 2.75 mm | Standard Deviation 0.717 |
| Treatment EE: Placebo | Pupillometry: Maximum Pupil Constriction (MPC) | 0.39 mm | Standard Deviation 0.537 |
Comparison: MPC: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Treatment D: M366 37.5 mg/1625 mg, Treatment E: Placebop-value: <0.0001ANOVA
Comparison: MPC: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.1268ANOVA
Comparison: MPC: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.0014ANOVA
Comparison: MPC: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: MPC: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Pupillometry: TA_AUE of MPC in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Pupillometry: TA_AUE of MPC in Treatment Phase | 1.565 mm | Standard Deviation 0.7042 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Pupillometry: TA_AUE of MPC in Treatment Phase | 2.355 mm | Standard Deviation 0.7394 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Pupillometry: TA_AUE of MPC in Treatment Phase | 1.317 mm | Standard Deviation 0.7014 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Pupillometry: TA_AUE of MPC in Treatment Phase | 1.888 mm | Standard Deviation 0.5855 |
| Treatment EE: Placebo | Pupillometry: TA_AUE of MPC in Treatment Phase | -0.153 mm | Standard Deviation 0.3308 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.012ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase
Any drug effects VAS measures other subjective effects experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (0 mm = 'definitely not') to 'extremely' (100 mm = 'definitely so'). Emax is the largest effect score between 0.5 to 8 hours post-dose.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 62.4 units on a scale | Standard Deviation 26.02 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 71.9 units on a scale | Standard Deviation 25.85 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 55.4 units on a scale | Standard Deviation 27.11 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 68.9 units on a scale | Standard Deviation 21.01 |
| Treatment EE: Placebo | Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase | 7.4 units on a scale | Standard Deviation 15.98 |
Comparison: Emax: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.063ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.4436ANOVA
Comparison: Emax: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emax: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase
Alertness/Drowsiness VAS measures the sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of 'neither drowsy nor alert' (score of 50 mm), on the left with 'very drowsy' (score of 0 mm) and on the right with 'very alert' (score of 100 mm). Alertness/Drowsiness VAS was calculated by subtracting pre-dose (baseline) value from each post-dose value. Emin is the smallest effect score between 0 to 8 hours post-dose.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 25.3 units on a scale | Standard Deviation 18.27 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 20.2 units on a scale | Standard Deviation 16.44 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 33.3 units on a scale | Standard Deviation 17.46 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 27.9 units on a scale | Standard Deviation 18.29 |
| Treatment EE: Placebo | Sedative and Other Effects: Emin of Alertness/Drowsiness VAS in Treatment Phase | 47.9 units on a scale | Standard Deviation 15.69 |
Comparison: Emin: Treatment C (low-dose M366) - Placebop-value: 0.0001ANOVA
Comparison: Emin: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.0014ANOVA
Comparison: Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.008ANOVA
Comparison: Emin: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: Emin: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase
Alertness/Drowsiness VAS measures the sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of 'neither drowsy nor alert' (score of 50 mm), on the left with 'very drowsy' (score of 0 mm) and on the right with 'very alert' (score of 100 mm). Alertness/Drowsiness VAS was calculated by subtracting pre-dose (baseline) value from each post-dose value. TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using trapezoidal rule.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | -12.103 units on a scale | Standard Deviation 14.4192 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | -16.919 units on a scale | Standard Deviation 17.3774 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | -6.751 units on a scale | Standard Deviation 13.867 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | -8.737 units on a scale | Standard Deviation 15.7482 |
| Treatment EE: Placebo | Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase | -0.348 units on a scale | Standard Deviation 6.8048 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: 0.0024ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: 0.0012ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.0037ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.0011ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA
Secondary
Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase
TA\_AUE is AUE0-8hr divided by time from dosing to the actual time of the 8-hour post-dose assessment using the trapezoidal rule.
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment AA: CL-108 15 mg/650 mg/25 mg | Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 29.720 units on a scale | Standard Deviation 21.4816 |
| Treatment BB: CL-108 22.5 mg/975 mg/37.5 mg | Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 38.504 units on a scale | Standard Deviation 20.2062 |
| Treatment CC: CL-108 30 mg/1300 mg/50 mg | Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 26.371 units on a scale | Standard Deviation 20.7356 |
| Treatment DD: CL-108 37.5 mg/1625 mg/62.5 mg | Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 34.030 units on a scale | Standard Deviation 19.3426 |
| Treatment EE: Placebo | Sedative and Other Effects: TA_AUE of Any Effects VAS in Treatment Phase | 1.537 units on a scale | Standard Deviation 3.7125 |
Comparison: TA\_AUE0-8hr: Treatment C (low-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment D (high-dose M366) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)p-value: 0.2335ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)p-value: 0.1808ANOVA
Comparison: TA\_AUE0-8hr: Treatment A (low-dose CL-108) - Placebop-value: <0.0001ANOVA
Comparison: TA\_AUE0-8hr: Treatment B (high-dose CL-108) - Placebop-value: <0.0001ANOVA