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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
12
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
Quotient Sciences
Ruddington, Nottingham, United Kingdom
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the time of maximum concentration (Tmax) of buprenorphine will be evaluated.
Time frame: 84 days
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the maximum concentration (Cmax) of buprenorphine will be evaluated.
Time frame: 84 days
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
Time frame: 84 days
Assessment of PK of INDV-6200 (buprenorphine)
The key parameter of the half life of buprenorphine will be evaluated.
Time frame: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of Tmax of norbuprenorphine will be evaluated.
Time frame: 84 days
Assessment of PK INDV-6200 (norbuprenorphine)
The key parameter of Cmax of norbuprenorphine will be evaluated.
Time frame: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of the half life of norbuprenorphine will be evaluated
Time frame: 84 days
Assessment of PK of INDV-6200 (norbuprenorphine)
The key parameter of the cumulative area under the curve (AUC) for each PK sample will be evaluated.
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Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine
Time frame: 84 days
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in physical examination.
Targeted physical examination will be performed focusing on abnormalities identified at screening and any changes. Clinically significant changes will be reported as adverse events (AE)
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in liver function tests.
Laboratory data will be summarized and any clinically significant abnormality will be reported as an AE
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in systolic and diastolic blood pressure
Blood pressure measurements (systolic and diastolic) will be summarized and any clinically significant abnormality will be reported as an AE
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by changes in heart rate
Heart rate will be summarized and any clinically significant changes will be reported as an AE
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) as assessed by electrocardiogram (ECG) changes
ECG intervals will be measured and summarized and any clinically significant changes will be reported as an AE
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of erythema
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of erythema will be summarized using counts and percentages at each timepoint by treatment
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of swelling
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of swelling will be summarized using counts and percentages at each timepoint by treatment
Time frame: Through day 84
Incidence of treatment emergence adverse events (TEAE) through assessment of the injection site for incidence of pain
Injection site assessment will be performed by the investigator using a 4 point scale. Levels of pain will be summarized using counts and percentages at each timepoint by treatment
Time frame: Through day 84