NCT03757559

A Trial to Evaluate the Abuse Potential of 3 Doses of GRT6005 in Adult Non-dependent Recreational Opioid Users

A Single-dose, Nested-randomized, Double-blind, Double-dummy, Placebo- and Active-controlled Crossover Trial to Evaluate the Abuse Potential of 3 Doses of GRT6005 in Adult Non-dependent Recreational Opioid Users

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 226 (actual)
• Sponsor: Tris Pharma, Inc. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The primary objective of this study was to evaluate the abuse potential of single doses of cebranopadol (GRT6005) relative to hydromorphone (immediate-release formulation \[IR\] and placebo in 48 non-dependent recreational opioid users. Secondary objectives were to evaluate the abuse potential of hydromorphone IR compared to placebo (trial validation), to evaluate the safety and tolerability of single doses of cebranopadol (200, 400, and 800 micrograms), and to evaluate pharmacokinetics (PK) of cebranopadol and optionally some of its metabolites.

Detailed description

The study comprised an Enrollment Visit, a Qualification Phase, a Treatment Phase with 7 double-blind treatment periods for each participant, and a Final Examination. In the Qualification Phase, all participants completed a naloxone challenge test to confirm that they were not opioid-dependent. The Objective Opioid Withdrawal Scale was used to record the signs or symptoms of withdrawal observed during the naloxone challenge test. Following the naloxone challenge test, participants received a single oral dose of hydromorphone immediate-release (IR) 12 milligrams (mg) and placebo in a double-blinded, randomized crossover manner to ensure that they could discriminate between an active drug and placebo and could tolerate hydromorphone IR 12 mg. After a washout phase of at least 3 days, participants could continue with the Treatment Phase. In the Treatment Phase, each participant received single oral doses of the 7 different investigational medicinal products (IMPs) (Treatment A to Treatment G) in 7 sequential treatment periods. The treatment sequences per participant were randomly assigned, except for one administration of placebo (Treatment G) which always followed the highest dose of cebranopadol (Treatment C). Each IMP administration was given under fasted conditions and was separated by a washout period of at least 14 days. Participants were confined to the study site from Day -1 until 48 hours after the first IMP administration in the Qualification Phase and from Day -1 until 56 hours after the IMP administration in the treatment periods. Pharmacodynamic assessments and blood sampling for pharmacokinetics were performed from pre-dose until 56 hours post-dose in each treatment period. The Final Examination was conducted 5 days to 10 days after the discharge from the last treatment period or upon early discontinuation from the study.

Conditions

• Abuse, Drug

Interventions

Type	Name	Description
DRUG	Cebranopadol 100 micrograms	Tablets were taken under fasted conditions with non-carbonated water.
DRUG	Cebranopadol 400 micrograms	Tablets were taken under fasted conditions with non-carbonated water.
DRUG	Hydromorphone hydrochloride 4 milligrams	Over-encapsulated immediate-release tablets were taken under fasted conditions with non-carbonated water.
DRUG	Placebo matching hydromorphone	Placebo matching over-encapsulated hydromorphone tablets were taken under fasted conditions with non-carbonated water.
DRUG	Placebo matching cebranopadol	Placebo matching cebranopadol tablets were taken under fasted conditions with non-carbonated water.

Timeline

• Start date: 2013-04-15
• Primary completion: 2014-03-08
• Completion: 2014-03-08
• First posted: 2018-11-29
• Last updated: 2021-07-15

Locations

1 site across 1 country: Canada