- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02712554
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
October 11, 2019 updated by: Charleston Laboratories, Inc
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
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.
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment A:CL-108 22.5mg/975mg/37.5mg
CL-108 22.5 mg/975 mg/37.5 mg tablet by mouth
|
7.5 mg/325 mg/12.5 mg tablet
Other Names:
|
Experimental: Treatment B:CL-108 37.5mg/1625mg/62.5mg
CL-108 37.5 mg/1625 mg/62.5 mg tablet by mouth
|
7.5 mg/325 mg/12.5 mg tablet
Other Names:
|
Active Comparator: Treatment C:M366 22.5mg/975mg
M366 22.5 mg/975 mg tablet by mouth
|
7.5 mg/325 mg tablet
Other Names:
|
Active Comparator: Treatment D: M366 37.5mg/1625mg
M366 37.5 mg/1625 mg tablet by mouth
|
7.5 mg/325 mg tablet
Other Names:
|
Placebo Comparator: Treatment E: Placebo
Placebo 0 mg tablet by mouth
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subjective Effects: Maximum Effect (Emax) and Minimum Effect (Emin) of High Visual Analog Scale (VAS) in Dose Selection Phase
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose)
|
Subjective Effects: Emax of Any Effects VAS in Dose Selection Phase
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours (post-dose)
|
Emax of Drug Liking VAS in Treatment Phase
Time Frame: 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.
|
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 and 24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Adverse Events in Dose Selection Phase
Time Frame: Up to visit 3 (Follow up)
|
AE=Adverse Event.
SAE=Serious adverse event.
TEAE=Treatment-emergent adverse event.
|
Up to visit 3 (Follow up)
|
Balance of Effects: Emin of Drug Liking VAS in Treatment Phase
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Positive Effects: TA_AUE of High VAS in Treatment Phase
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Positive Effects: Emax of Good Effects VAS in Treatment Phase
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Sedative and Other Effects: TA_AUE of Alertness/Drowsiness VAS in Treatment Phase
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Sedative and Other Effects: Emax of Any Effects VAS in Treatment Phase
Time Frame: 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.
|
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
Time Frame: 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.
|
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
Time Frame: 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.
|
0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose)
|
Change From Baseline in Number of Errors (Any Errors) in CRT Test in Treatment Phase
Time Frame: 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.
|
0 (Baseline, pre-dose), 1, 2, 4, 8 and 24 hours (post-dose)
|
Pupillometry: Maximum Pupil Constriction (MPC)
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Pupillometry: TA_AUE of MPC in Treatment Phase
Time Frame: 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.
|
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours (post-dose)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Bernard P Schachtel, M.D, Charleston Laboratories
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2015
Primary Completion (Actual)
September 1, 2015
Study Completion (Actual)
September 1, 2015
Study Registration Dates
First Submitted
March 15, 2016
First Submitted That Met QC Criteria
March 17, 2016
First Posted (Estimate)
March 18, 2016
Study Record Updates
Last Update Posted (Actual)
October 14, 2019
Last Update Submitted That Met QC Criteria
October 11, 2019
Last Verified
October 1, 2019
More Information
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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