A Study in Opioid-Experienced, Non-Dependent Recreational... | NCT02712554 | Trialant
NCT02712554
Sponsor
Charleston Laboratories, Inc
Status
Completed
Last Update Posted
Oct 14, 2019Actual
Enrollment
40Actual
Phase
Phase 1
Conditions
Pain
Nausea
Vomiting
Interventions
CL-108
M366
Placebo
Countries
Not provided
Protocol Section
Identification Module
NCT ID
NCT02712554
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLCT-007
Secondary IDs
Not provided
Brief Title
A Study in Opioid-Experienced, Non-Dependent Recreational Drug Users to Determine the Abuse Potential and Safety of CL-108 Tablets Administered Via the Oral Route
Official Title
A Randomized, Double-Blind, Placebo and Active-Controlled, Crossover Study in Opioid-Experienced, Non-Dependent Recreational Drug Users to Determine the Abuse Potential and Safety of CL-108 Tablets Administered Via the Oral Route
Acronym
Not provided
Organization
Charleston Laboratories, IncINDUSTRY
Status Module
Record Verification Date
Oct 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 2015
Primary Completion Date
Sep 2015Actual
Completion Date
Sep 2015Actual
First Submitted Date
Mar 15, 2016
First Submission Date that Met QC Criteria
Mar 17, 2016
First Posted Date
Mar 18, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 14, 2016
Results First Submitted that Met QC Criteria
Oct 11, 2019
Results First Posted Date
Oct 14, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 11, 2019
Last Update Posted Date
Oct 14, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Charleston Laboratories, IncINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
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.
Conditions Module
Conditions
Pain
Nausea
Vomiting
Keywords
Pain
Nausea
Vomiting
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
40Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Treatment A:CL-108 22.5mg/975mg/37.5mg
Experimental
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
Drug: CL-108
Treatment B:CL-108 37.5mg/1625mg/62.5mg
Experimental
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
Drug: CL-108
Treatment C:M366 22.5mg/975mg
Active Comparator
M366 22.5 mg/975 mg tablet by mouth
Drug: M366
Treatment D: M366 37.5mg/1625mg
Active Comparator
M366 37.5 mg/1625 mg tablet by mouth
Drug: M366
Treatment E: Placebo
Placebo Comparator
Placebo 0 mg tablet by mouth
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
CL-108
Drug
7.5 mg/325 mg/12.5 mg tablet
Treatment A:CL-108 22.5mg/975mg/37.5mg
Treatment B:CL-108 37.5mg/1625mg/62.5mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
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.
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.
Balance of Effects: Emin of Drug Liking VAS in Treatment Phase
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
55 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Bernard P Schachtel, M.D
Charleston Laboratories
Study Chair
Locations
Not provided
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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
FG001
Periods
Title
Milestones
Reasons Not Completed
Part A: Dose Selection Phase
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Not provided
Primary Purpose
Basic Science
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Low-dose CL-108 and High-dose CL-108
M366
Drug
7.5 mg/325 mg tablet
Treatment C:M366 22.5mg/975mg
Treatment D: M366 37.5mg/1625mg
Low-dose M366 and High-dose M366
Placebo
Drug
Treatment E: Placebo
0 mg tablet
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
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.
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
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.
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.
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.
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
FG00012 subjects
FG0010 subjects
COMPLETED
FG00012 subjects
FG0010 subjectsSubjects who participated in Dose Selection Phase were not eligible to participate in Part B.
NOT COMPLETED
FG0000 subjects
FG0010 subjects
Part B: Qualification Phase
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00161 subjects
COMPLETED
FG0000 subjects
FG00140 subjects
NOT COMPLETED
FG0000 subjects
FG00121 subjects
Type
Comment
Reasons
Drug Discrimination Failure
FG0000 subjects
FG00113 subjects
Sponsor Decision
FG0000 subjects
FG001
Part B: Treatment Phase
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00140 subjects
COMPLETED
FG0000 subjects
FG00137 subjects
NOT COMPLETED
FG0000 subjects
FG0013 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
Withdrawal by Subject
FG0000 subjects
FG001
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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
BG001
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
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00012
BG00140
BG00252
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
Between 18 and 65 years
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0018
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
Title
Measurements
BG00010
BG00134
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Hispanic or Latino
Title
Measurements
BG0003
BG0014
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
Title
Measurements
BG00012
BG00140
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
Safety population.
Parameters were not calculated for subjects who experienced emesis within the first 3 hours post-dose.
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.
Safety population.
Parameters were not calculated for subjects who experienced emesis within the first 3 hours post-dose.
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.
Naloxone 0.2 mg bolus intravenously followed by a 10 mL saline flush
CL-108 15 mg/650 mg/25 mg
CL-108 22.5 mg/975 mg/37.5 mg
CL-108 30 mg/1300 mg/50 mg
CL-108 37.5 mg/1625 mg/62.5 mg
Placebo 0 mg
Units
Counts
Participants
OG00012
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.
ITT population.
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
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.
ITT population.
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
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.
ITT population.
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
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.
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
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.
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.
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
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.
ITT population
Posted
Mean
Standard Deviation
units on a scale
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours
ID
Title
Description
OG000
Treatment A: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
OG001
Treatment B: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG002
Treatment C: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
OG003
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
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.
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.
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.
Up to visit 3 (Follow up) for Dose Selection phase and Up to Day 24 (Follow up) for Treatment phase
Description
Total 12 subjects in Dose Selection and 40 subjects in Treatment Phase are enrolled and received at least 1 dose of study drug and were included in the Safety population.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Dose Selection AA: CL-108 15 mg/650 mg/25 mg
CL-108 15 mg/650 mg/25 mg tablet by mouth
0
2
0
2
EG001
Dose Selection BB: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
0
2
2
2
EG002
Dose Selection CC: CL-108 30 mg/1300 mg/50 mg
CL-108 30 mg/1300 mg/50 mg tablet by mouth
0
2
1
2
EG003
Dose Selection CC: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
0
2
2
2
EG004
Dose Selection EE: Placebo
Placebo 0 mg tablet by mouth
0
4
0
4
EG005
Treatment AA: CL-108 22.5 mg/975 mg/37.5 mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
0
40
30
40
EG006
Treatment BB: CL-108 37.5 mg/1625 mg/62.5 mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
0
39
34
39
EG007
Treatment CC: M366 22.5 mg/975 mg
M366 22.5 mg/975 mg tablet by mouth
0
38
28
38
EG008
Treatment DD: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
0
39
31
39
EG009
Treatment EE: Placebo
Placebo 0 mg tablet by mouth
0
39
14
39
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG0030 affected2 at risk
EG0040 affected4 at risk
EG00513 affected40 at risk
EG00623 affected39 at risk
EG00714 affected38 at risk
EG00817 affected39 at risk
EG0091 affected39 at risk
Pruritus Generalised
Skin and subcutaneous tissue disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Euphoric Mood
Psychiatric disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0021 affected2 at risk
EG003
Irritability
Psychiatric disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Bruxism
Psychiatric disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Abnormal Dreams
Psychiatric disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0012 affected2 at risk
EG0020 affected2 at risk
EG003
Headache
Nervous system disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Disturbance in Attention
Nervous system disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Abdominal Pain Upper
Gastrointestinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Feeling Hot
General disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Feeling of Relaxation
General disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Vision Blurred
Eye disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Hot Flush
Vascular disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Hypoacusis
Ear and labyrinth disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0020 affected2 at risk
EG003
Photophobia
Eye disorders
MedDRA (Unspecified)
Systematic Assessment
EG0000 affected2 at risk
EG0010 affected2 at risk
EG0021 affected2 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
Not provided
Results Disclosure Restriction on PI(s)?
No
Other Details
Not provided
Point of Contact
Title
Organization
Phone
Extension
Email
Chief Commercial Officer
Charleston Laboratories, Inc.
561-748-2007
cliregulatory@charlestonlabs.com
ID
Term
D010146
Pain
D009325
Nausea
D014839
Vomiting
Ancestor Terms
ID
Term
D009461
Neurologic Manifestations
D012816
Signs and Symptoms
D013568
Pathological Conditions, Signs and Symptoms
D012817
Signs and Symptoms, Digestive
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D013607
Tablets
Ancestor Terms
ID
Term
D004304
Dosage Forms
D004364
Pharmaceutical Preparations
Browse Leaves
Not provided
Browse Branches
Not provided
4 subjects
Withdrawal by Subject
FG0000 subjects
FG0013 subjects
Adverse Event
FG0000 subjects
FG0011 subjects
1 subjects
Other
FG0000 subjects
FG0011 subjects
BG00012
BG00140
BG00252
>=65 years
BG0000
BG0010
BG0020
12
Male
BG0008
BG00132
BG00240
44
Black or African American
Title
Measurements
BG0001
BG0013
BG0024
American Indian or Alaska Native
Title
Measurements
BG0000
BG0011
BG0021
Multiple
Title
Measurements
BG0000
BG0012
BG0022
Asian
Title
Measurements
BG0001
BG0010
BG0021
7
Not Hispanic or Latino
Title
Measurements
BG0009
BG00136
BG00245
52
1
OG0044
94.0
OG0042.3± 4.50
Emin
Title
Measurements
OG0003.0± 4.24
OG00123.5± 3.54
OG00242.0± 11.31
OG0037.0
OG00460.8± 20.84
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
OG004
Treatment EE: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG0002
OG0012
OG0022
OG0031
OG0044
Title
Denominators
Categories
Title
Measurements
OG00086.0± 19.80
OG00148.5± 26.16
OG00275.0± 35.36
OG00394.0
OG0044.3± 5.68
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00077.3± 14.68
OG00181.4± 13.10
OG00274.4± 13.75
OG00379.8± 13.07
OG00454.5± 9.95
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
ANOVA
<0.0001
Superiority or Other (legacy)
OG003
OG004
ANOVA
<0.0001
Superiority or Other (legacy)
OG000
OG002
ANOVA
0.2344
Superiority or Other (legacy)
OG001
OG003
ANOVA
0.4737
Superiority or Other (legacy)
OG000
OG004
ANOVA
<0.0001
Superiority or Other (legacy)
OG001
OG004
ANOVA
<0.0001
Superiority or Other (legacy)
Title
Denominators
Categories
Total number of AEs
Title
Measurements
OG00016
Total Number of TEAEs
Title
Measurements
OG00014
Number of SAEs
Title
Measurements
OG0000
Number of AEs leading to Discontinuation
Title
Measurements
OG0000
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00049.0± 3.16
OG00146.6± 12.16
OG00244.8± 11.67
OG00346.5± 12.96
OG00447.1± 11.42
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00012.071± 10.4456
OG00113.772± 10.6773
OG0029.773± 12.4254
OG00311.162± 12.8093
OG0041.183± 5.0571
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Emax
Title
Measurements
OG00070.4± 17.77
OG00175.8± 17.16
OG00265.2± 17.89
OG00371.1± 16.81
OG00452.2± 8.74
Emin
Title
Measurements
OG00061.2± 17.07
OG00166.7± 19.96
OG00257.2± 18.85
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.1267
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.1767
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG002
OG004
Emin: Treatment C (low-dose M366) - Placebo
ANOVA
0.0119
Superiority or Other (legacy)
OG003
OG004
Emin: Treatment D (high-dose M366) - Placebo
ANOVA
0.0025
Superiority or Other (legacy)
OG000
OG002
Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.1679
Superiority or Other (legacy)
OG001
OG003
Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.0318
Superiority or Other (legacy)
OG000
OG004
Emin: Treatment A (low-dose CL-108) - Placebo
ANOVA
0.0002
Superiority or Other (legacy)
OG001
OG004
ANOVA
<.0001
Superiority or Other (legacy)
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Emax
Title
Measurements
OG00074.6± 18.98
OG00175.2± 18.49
OG00268.9± 19.89
OG00371.3± 20.51
OG00451.1± 12.45
Emin
Title
Measurements
OG00066.4± 19.85
OG00169.3± 21.07
OG00260.9± 21.19
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.0858
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.2877
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG002
OG004
Emin: Treatment C (low-dose M366) - Placebo
ANOVA
0.0009
Superiority or Other (legacy)
OG003
OG004
Emin: Treatment D (high-dose M366) - Placebo
ANOVA
0.0001
Superiority or Other (legacy)
OG000
OG002
Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.1130
Superiority or Other (legacy)
OG001
OG003
Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.0575
Superiority or Other (legacy)
OG000
OG004
Emin: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
Emin: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00058.9± 29.05
OG00171.8± 26.07
OG00254.6± 28.41
OG00367.5± 22.76
OG0045.4± 12.92
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.4025
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.3184
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG0001.055± 2.8942
OG00127.850± 21.6226
OG00236.363± 21.0716
OG00324.500± 20.8024
OG00432.050± 20.7004
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
TA_AUE0-8hr: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
TA_AUE0-8hr: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.2628
Superiority or Other (legacy)
OG001
OG003
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.2262
Superiority or Other (legacy)
OG000
OG004
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG0006.3± 15.06
OG00159.3± 29.42
OG00268.3± 25.99
OG00352.5± 29.35
OG00462.2± 23.24
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.1839
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.1751
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00028.108± 22.0759
OG00134.894± 20.5885
OG00225.541± 23.1053
OG00329.327± 19.7001
OG0041.140± 2.9074
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
TA_AUE0-8hr: Treatment C (low-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG003
OG004
TA_AUE0-8hr: Treatment D (high-dose M366) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG000
OG002
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.4013
Superiority or Other (legacy)
OG001
OG003
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.0736
Superiority or Other (legacy)
OG000
OG004
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG001
OG004
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Placebo
ANOVA
<.0001
Superiority or Other (legacy)
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00014.8± 21.89
OG00130.1± 29.35
OG00220.1± 20.61
OG00336.1± 30.39
OG0042.4± 9.68
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<0.001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<0.001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.2223
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.1638
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
0.0041
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<0.001
Superiority or Other (legacy)
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG0005.487± 10.5253
OG00112.535± 16.0605
OG0027.171± 9.8243
OG00313.830± 14.9453
OG0040.217± 0.9084
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
TA_AUE0-8hr: Treatment C (low-dose M366) - Placebo
ANOVA
0.0001
Superiority or Other (legacy)
OG003
OG004
TA_AUE0-8hr: Treatment D (high-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG000
OG002
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.2706
Superiority or Other (legacy)
OG001
OG003
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.5507
Superiority or Other (legacy)
OG000
OG004
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Placebo
ANOVA
0.0047
Superiority or Other (legacy)
OG001
OG004
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00025.3± 18.27
OG00120.2± 16.44
OG00233.3± 17.46
OG00327.9± 18.29
OG00447.9± 15.69
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emin: Treatment C (low-dose M366) - Placebo
ANOVA
0.0001
Superiority or Other (legacy)
OG003
OG004
Emin: Treatment D (high-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG000
OG002
Emin: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.0014
Superiority or Other (legacy)
OG001
OG003
Emin: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.0080
Superiority or Other (legacy)
OG000
OG004
Emin: Treatment A (low-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG001
OG004
Emin: Treatment B (high-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
Treatment D: M366 37.5 mg/1625 mg
M366 37.5 mg/1625 mg tablet by mouth
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG000-12.103± 14.4192
OG001-16.919± 17.3774
OG002-6.751± 13.8670
OG003-8.737± 15.7482
OG004-0.348± 6.8048
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
TA_AUE0-8hr: Treatment C (low-dose M366) - Placebo
ANOVA
0.0024
Superiority or Other (legacy)
OG003
OG004
TA_AUE0-8hr: Treatment D (high-dose M366) - Placebo
ANOVA
0.0012
Superiority or Other (legacy)
OG000
OG002
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.0037
Superiority or Other (legacy)
OG001
OG003
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.0011
Superiority or Other (legacy)
OG000
OG004
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG001
OG004
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG004
Treatment E: Placebo
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00062.4± 26.02
OG00171.9± 25.85
OG00255.4± 27.11
OG00368.9± 21.01
OG0047.4± 15.98
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
Emax: Treatment C (low-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG003
OG004
Emax: Treatment D (high-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG000
OG002
Emax: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.0630
Superiority or Other (legacy)
OG001
OG003
Emax: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.4436
Superiority or Other (legacy)
OG000
OG004
Emax: Treatment A (low-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG001
OG004
Emax: Treatment B (high-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
Placebo 0 mg tablet by mouth
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00337
OG00437
Title
Denominators
Categories
Title
Measurements
OG00029.720± 21.4816
OG00138.504± 20.2062
OG00226.371± 20.7356
OG00334.030± 19.3426
OG0041.537± 3.7125
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG004
TA_AUE0-8hr: Treatment C (low-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG003
OG004
TA_AUE0-8hr: Treatment D (high-dose M366) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG000
OG002
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Treatment C (low-dose M366)
ANOVA
0.2335
Superiority or Other (legacy)
OG001
OG003
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Treatment D (high-dose M366)
ANOVA
0.1808
Superiority or Other (legacy)
OG000
OG004
TA_AUE0-8hr: Treatment A (low-dose CL-108) - Placebo
ANOVA
<0.0001
Superiority or Other (legacy)
OG001
OG004
TA_AUE0-8hr: Treatment B (high-dose CL-108) - Placebo