NCT03715634

Study of a Novel Subcutaneous Depot Formulation of Buprenorphine

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Novel Subcutaneous Depot Formulation of Buprenorphine (INDV-6200) in Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Indivior Inc. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

INDV-6200 is being developed for the treatment of opioid dependency and is expected to provide sustained buprenorphine plasma concentrations. The study will be done in healthy volunteers and will administer a non-therapeutic dose of INDV-6200. Study Period 1 will evaluate the oral tolerability of sublingual (SL) buprenorphine dosed over 3 days. Period 2 will administer the investigational medicinal product (IMP) or volume matched placebo.

Detailed description

INDV-6200 is a novel buprenorphine subcutaneous (SC) depot formulation being developed for the treatment of opioid dependency. It is expected to provide sustained buprenorphine plasma concentrations to achieve consistent and optimal occupancy of mu-opioid receptors in the brain, for the treatment of opioid use disorder. A related subcutaneously injected, extended-release product of buprenorphine base has demonstrated sustained therapeutic plasma levels of buprenorphine over a minimum of 1 month. Extensive experience gained from RBP-6000 allowed the development of an allometric model which has been used to predict the in vivo performance of INDV-6200. The preclinical pharmacokinetic (PK) data and the predictions from allometric scaling indicate that INDV-6200 is expected to display a similar PK profile as RBP-6000. Therefore, the main objective of this study is to investigate the PK properties of this new, related formulation using a low dose with a large safety margin. Period 1 will be used to evaluate the oral tolerability of SL buprenorphine (SUBUTEX; non-investigational medicinal product \[nIMP\]) dosed over 3 days. Period 2 will involve administration of the IMP (INDV-6200) or volume-matched placebo; (low dose in Cohort A or alternative dose in optional Cohort B), to evaluate PK and safety of this novel formulation. Both periods will also include a series of Nalorex (nIMP) administrations to antagonise potential opioid effects from buprenorphine. Based on modeling and simulation, the dose proposed for Cohort A is expected to give similar plasma buprenorphine exposure to that obtained with the same SC dose of RBP-6000. If buprenorphine plasma exposure is lower than predicted, there is an optional second cohort (Cohort B), which may be used to explore another dose level of INDV-6200 predicted. As this is a Phase I study, using a non-therapeutic dose of INDV-6200, the most relevant population is healthy subjects as this allows a characterisation of safety, tolerability and PK for a new molecular entity in a homogeneous population without potential biases from a patient population. In order to avoid any interaction with other medication, no co-medication will be allowed.

Conditions

• Opioid-use Disorder

Interventions

Type	Name	Description
DRUG	INDV-6200	Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
DRUG	Placebo	Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo
DRUG	SL Buprenorphine	All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability
DRUG	Nalorex	Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine

Timeline

• Start date: 2017-09-20
• Primary completion: 2018-06-07
• Completion: 2018-06-07
• First posted: 2018-10-23
• Last updated: 2019-03-04

Locations

1 site across 1 country: United Kingdom