Study of a Novel Subcutaneous Depot Formulation of Buprenorphine
Condition: Opioid-use Disorder
MeSH terms: Opioid-Related Disorders
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): INDV-6200; Placebo; SL Buprenorphine; Nalorex
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo; Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo; All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability; Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine
Other intervention name(s): Subutex
Intervention MeSH terms: Buprenorphine
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Treatment