Buprenorphine-Fentanyl Interaction Study

Summary

An increase in overdose deaths has been attributed to widespread access to fentanyl and carfentanyl. The study is designed to determine if buprenorphine can change the respiratory depression response to intravenous (IV) fentanyl.

Conditions

• Healthy
• Opioid Use

Interventions

DRUG

Buprenorphine Injectable Solution - Part A

Buprenorphine intravenous (IV) injection given as a primed-continuous infusion. Low Dose: initial bolus (0.05 mg/70 kg) administered over 15 minutes and infusion continued (0.02 mg/70 kg/hour infusion rate) to complete 360 minutes of administration targeting 0.2 ng/ml. High Dose: initial bolus (0.125 mg/70 kg) administered over 15 minutes and infusion continued (0.05 mg/70 kg/hour infusion rate) to complete 360 minutes of administration targeting 0.5 ng/ml. Administration of buprenorphine was flexible and infusion rates were selected to target approximately 25 to 50% respiratory depression.

DRUG

Placebo - Parts A + B

0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration.

DRUG

Fentanyl - Part A

Participant received up to four fentanyl doses: 0.075, 0.15, 0.25, and 0.35 mg/70 kg in Periods 1 and 2. Fentanyl boluses were administered over 90 seconds by dose escalation +2hr, +3hr, +4hr and +5hr after starting administration of buprenorphine/ placebo. Administration of fentanyl was flexible and bolus doses were selected to elicit moderate to more severe respiratory depression with apnoea ≥20 seconds.

DRUG

Ondansetron - Parts A + B

A non-investigational intervention administered as an infusion prior to investigation intervention. 4 mg of ondansetron was administered to manage the expected gastrointestinal side effect (nausea, vomiting) to buprenorphine.

DRUG

Buprenorphine Injectable Solution - Part B

Buprenorphine intravenous (IV) injection given as a primed-continuous infusion. Low Dose: initial bolus (0.25 mg/70 kg) administered over 15 minutes and infusion continued (0.1 mg/70 kg/hour infusion rate) to complete 360 minutes of administration targeting 1 ng/ml. Mid Dose: initial bolus (0.5 mg/70 kg) administered over 15 minutes and infusion continued (0.2 mg/70 kg/hour infusion rate) to complete 360 minutes of administration targeting 2 ng/ml. High Dose: initial bolus (1.25 mg/70 kg) administered over 15 minutes and infusion continued (0.5 mg/70 kg/hour infusion rate) to complete 360 minutes of administration targeting 5 ng/ml.

DRUG

Fentanyl - Part B

Participant received up to four fentanyl doses: 0.25, 0.35, 0.5, and 0.7 mg/70 kg in Periods 1 and 2. Fentanyl boluses were administered over 90 seconds by dose escalation +2hr, +3hr, +4hr and +5hr after starting administration of buprenorphine/ placebo.

DRUG

Oxycodone - Part B

All opioid-tolerant participants in Part B were transitioned to oral oxycodone at least 48 hours before Period 1 to ensure washout of the participants' regular opioids and a stable dose of oxycodone with an adequate bridging schedule reached. Oxycodone is a non-investigational intervention.

Sponsors & Collaborators

• Indivior Inc.

  lead INDUSTRY

Principal Investigators

• Geert J Groeneveld · Center for Human Drug Research

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-03-22

Primary Completion

2019-01-04

Completion

2019-01-04

Countries

• Netherlands

Study Locations