A Trial to Evaluate the Abuse Potential of 3 Doses of GRT6005 in Adult Non-dependent Recreational Opioid Users
Condition: Abuse, Drug
MeSH terms: Substance-Related Disorders
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Cebranopadol 100 micrograms; Cebranopadol 400 micrograms; Hydromorphone hydrochloride 4 milligrams; Placebo matching hydromorphone; Placebo matching cebranopadol
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Tablets were taken under fasted conditions with non-carbonated water.; Tablets were taken under fasted conditions with non-carbonated water.; Over-encapsulated immediate-release tablets were taken under fasted conditions with non-carbonated water.; Placebo matching over-encapsulated hydromorphone tablets were taken under fasted conditions with non-carbonated water.; Placebo matching cebranopadol tablets were taken under fasted conditions with non-carbonated water.
Other intervention name(s): Dilaudid (Trade Mark) 4 mg
Intervention MeSH terms: Hydromorphone
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Nested-randomized, single site, double-blind, double-dummy, placebo- and active-controlled, crossover design with administration of a single oral dose. Based on the assigned treatment sequence, each participant was randomly allocated to receive a single oral dose of the investigational medicinal product (IMP) in each of 7 periods. One administration of placebo (Treatment G) always followed cebranopadol 800 micrograms (Treatment C). Each IMP administration was given under fasted conditions and was separated by a washout period of at least 14 days.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cebranopadol; Hydromorphone; Drug liking