Study of a Novel Subcutaneous Depot Formulation of Buprenorphine

NCT ID: NCT03715634

Last Updated: 2019-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-20
• Study Completion Date: 2018-06-07

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Depot buprenorphine (INDV-6200)

Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive depot buprenorphine

Group Type: EXPERIMENTAL

INDV-6200

Intervention Type: DRUG

Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo

SL Buprenorphine

Intervention Type: DRUG

All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability

Nalorex

Intervention Type: DRUG

Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine

Placebo

Period 1 subjects will receive SL buprenorphine to confirm tolerance to product Period 2 subjects will receive volume-matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo

SL Buprenorphine

Intervention Type: DRUG

All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability

Nalorex

Intervention Type: DRUG

Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine

Interventions

INDV-6200

Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo

Intervention Type: DRUG

Placebo

Subjects will be randomized in a 3:1 ratio to receive either depot buprenorphine or volume-matched placebo

Intervention Type: DRUG

SL Buprenorphine

All subjects will receive SL buprenorphine as non-investigational IMP to confirm tolerability

Intervention Type: DRUG

Nalorex

Both Periods will include series of nalorex administrations to antagonize potential opioid effects from buprenorphine

Intervention Type: DRUG

Other Intervention Names

Subutex

Eligibility Criteria

Inclusion Criteria

1. Healthy males or non-pregnant, non-lactating females

2. Body mass index of 18.0-33.0 kg/m2 or, if outside the range, considered not clinically significant by the Investigator

3. Willing and able to communicate and participate in the whole study

4. Provide written informed consent prior to any study specific procedures

5. Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment, ECG, and laboratory investigations

6. Males and females must agree to use an adequate method of contraception

7. Tolerated SL buprenorphine and nalorex during Period 1

Exclusion Criteria

1. Medical history of opioid-related adverse reactions

2. History of clinically significant alcohol/drug abuse in the previous 5 years

3. Received any investigational medicinal product within the previous 3 months

4. Study site employees or immediate family members of study site or sponsor employee

5. Previously enrolled in the study

6. Regular alcohol consumption in males greater than 21 units/week and females greater than 14 units/week

7. Current smokers and those who have smoked within the last 6 months

8. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months

9. Do not have suitable veins for multiple venipunctures

10. Clinically significant abnormal biochemistry, haematology or urinalysis

11. Positive urine drug screen at screening and admission for each period

12. Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results

13. History of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease, or psychiatric disorder

14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

15. Clinically significant allergy requiring treatment. Hayfever is allowed unless active

16. Donation or loss of greater than 400 mL of blood within the previous 3 months

17. Taking or have taken, any prescribed or over-the counter drugs or herbal remedies in the 14 days before IMP administrations. Exceptions may apply

18. Injection sites containing any skin discolouration, tattoo, scar tissue or other abnormalities that may impair injection site assessment

19. Any food or drink containing grapefruit or Seville oranges within 7 days prior to first dose of buprenorphine

20. Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 and/or cytochrome 450 2C8 enzyme within 30 days prior to first dose of study drug

21. Clinically significant abnormal ECG, including QT interval corrected using Fridericia's formula of greater than 450msec in males and greater than 470 msec in females

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Indivior Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nand Singh

Role: PRINCIPAL_INVESTIGATOR

Quotient Sciences

Locations

Quotient Sciences

Ruddington, Nottingham, United Kingdom

Countries

United Kingdom

Other Identifiers

INDV-6200-101

Identifier Type: -

Identifier Source: org_study_id