Assessment of Abuse Potential of Cebranopadol in Humans

A Single-dose, Randomized, Double-blind, Placebo- and Active-controlled Crossover Trial to Evaluate the Abuse Potential of Two Doses of Cebranopadol in Adult Nondependent Recreational Opioid Users

This study will be conducted to evaluate the abuse potential of single doses of cebranopadol as compared with oxycodone, tramadol and matching placebo in recreational drug users.

Study Overview

• Status: Completed
• Conditions: Human Abuse Potential
• Intervention / Treatment: Drug: Cebranopadol 600 µg; Drug: Cebranopadol 1000 µg; Drug: Oxycodone 40 mg; Drug: Tramadol 600 mg; Drug: Placebo

Detailed Description

Randomized, single site, double-blind, placebo- and active-controlled, crossover, single oral dose, Phase 1 trial, in non dependent recreational opioid users

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Ohio Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Adult men or women aged 18 to 55 years, inclusive
• History of recreational opioid use defined as non therapeutic use at least 10 times in the subject's lifetime and at least once in the 12 weeks prior to the Enrollment Visit
• Body mass index between 19 kg/m2 and 32 kg/m2 inclusive, with a body weight of not less than 50 kg at Enrollment
• Subjects must be in good health as determined by medical history, physical examination, 12 lead electrocardiogram (ECG), and vital signs (pulse rate, systolic blood pressure and diastolic blood pressure, respiratory rate, and oxygen saturation using pulse oximetry) at Enrollment

Exclusion Criteria:

• Exclusion Criteria for Enrollment:
• Self-reported history of drug or alcohol dependence (lifetime) other than caffeine or nicotine as defined by DSM IV-TR criteria
• Current treatment or treatment within their lifetime for substance disorders, other than treatment for smoking cessation
• Positive or missing alcohol breath test at Enrollment; the alcohol breath test can be repeated and/or the subject rescheduled at the discretion of the investigator or designee
• Pregnant or breastfeeding or missing pregnancy test
• Unwillingness or inability to abstain from recreational drug use for the duration of the trial
• Current consumption of greater than 20 cigarettes per day or inability to abstain from smoking (or use of any nicotine-containing substance) for at least 8 hours
• Participation in another clinical trial within 30 days prior to Enrollment that resulted in the administration of at least 1 dose of IMP
• Diseases or conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Subjects with a history of cholecystectomy are not excluded
• Prolongation of QTcF (after repeated assessment) at Enrollment, i.e., >450 ms for men or >470 ms for women, or presence of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia), or use of concomitant medications that prolong the QT interval
• History of orthostatic hypotension or other cardiovascular diseases
• Any clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise the subject's safety during trial participation, e.g., significant pulmonary, gastrointestinal, cardiac, endocrine, metabolic, neurological, or psychiatric disorders
• Definite or suspected history of drug allergy or hypersensitivity to opioids or opioid antagonists
• Use of prescription medications within the longer of 14 days or 5 half-lives or use of over-the-counter medications within the longer of 7 days or 5 half-lives prior to dosing, exceptions may be made on a case-by-case basis (e.g., for medications with a short half-life or for topical medications) if approved by the medical monitor in agreement with the investigator
• Any contraindication for naloxone, oxycodone IR, or tramadol IR administration
• Not able to abstain from consumption of beverages or food containing caffeine (tea, coffee, cola, chocolate, etc.) or alcohol from 2 days prior to each Day 1 until discharge from the research unit; beverages or food containing quinine (e.g., bitter lemon, tonic water) from 1 week before Day 1 of the Qualification Phase until the final examination; grapefruit juice (sweet or sour) or Seville oranges from 1 week before Day 1 of the Qualification Phase until the final examination.
• Blood loss of 500 mL or more within 4 weeks before dosing in the treatment phase in this trial, including blood donation. Planned blood donations during the trial and up to 12 weeks after the Final Examination
• History of seizure disorder including unprovoked seizure and/or epilepsy or any condition associated with a significant risk for seizure disorder or epilepsy at the Enrollment Visit at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cebranopadol 600 µg; Single oral dose of 6 capsules containing 3 cebranopadol 200 µg tablets and placebo	Drug: Cebranopadol 600 µg; Participants will be administered a single dose of 6 capsules containing cebranopadol and placebo in a randomized crossover manner; Other Names: Treatment Phase
Experimental: Cebranopadol 1000 µg; Single oral dose of 6 capsules containing 5 cebranopadol 200 µg tablets and placebo	Drug: Cebranopadol 1000 µg; Participants will be administered a single dose of 6 capsules containing cebranopadol and placebo in a randomized crossover manner; Other Names: Treatment Phase
Active Comparator: Oxycodone 40 mg; Single oral dose of 6 capsules containing 2 oxycodone 20 mg and placebo	Drug: Oxycodone 40 mg; Participants will be administered a single dose of 6 capsules containing oxycodone and placebo in a randomized crossover manner; Other Names: Qualification Phase/ Treatment Phase
Active Comparator: Tramadol 600 mg; Single oral dose of 6 capsules containing 6 tramadol 100 mg tablets	Drug: Tramadol 600 mg; Participants will be administered a single dose of 6 capsules containing tramadol in a randomized crossover manner; Other Names: Qualification Phase/ Treatment Phase
Placebo Comparator: Placebo; Single oral dose of 6 capsules containing placebo	Drug: Placebo; Participants will be administered a single dose of 6 capsules containing placebo in a randomized crossover manner; Other Names: Qualification Phase/ Treatment Phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Liking Visual analog scale (VAS) Emax	The scale is a 0-100-point scale: 0 = "Strong disliking"; 50 = "Neither like nor dislike"; 100 = "Strong liking"	Treatment Phase: Intervals from predose to 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS rating for Overall Liking	The scale is a 0-100-point scale: 0 = "Strong Disliking", 50 = "Neither Like nor Dislike", 100 = "Strong Liking"	Treatment Phase: Intervals from predose to 48 hours post-dose
VAS rating for Take Drug Again	The scale is a 0-100-point scale: 0 = "Definitely would not"; 50 = "Do not care"; 100 = "Definitely would"	Treatment Phase: Intervals from predose to 48 hours post-dose
Pupillometry	Data from a series of frames will be used in the calculation, and the final display will show the weighted average and standard deviation of the pupil size. Measurements will be collected under mesopic lighting conditions	Treatment Phase: Intervals from predose to 48 hours post-dose
Multi-Tasking Test	Formerly known as the Attention Switching Task (AST), is a test of executive function which provides a measure of the ability to use multiple sources of potentially conflicting information to guide behavior.	Treatment Phase: Intervals from predose to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Tris Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Actual): July 12, 2022
• Study Completion (Actual): July 12, 2022

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: opioid; pain; abuse
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Tramadol; Oxycodone
• Other Study ID Numbers: PARK-101-HAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No