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Buprenorphine Injectable- Part A · 1 trial · 2 indications
Peak ventilatory depression (change in minute ventilation) will be calculated based on a 1-minute average of the ventilation data of each individual subject/patient. For buprenorphine or placebo, absolute changes and percentage changes are calculated from the baseline value. For fentanyl, absolute changes and percentage changes for each bolus are calculated from the baseline value and from the pre-fentanyl baseline value immediately before the first fentanyl bolus
| Arm | Type | Description |
|---|---|---|
| Part A (Healthy Participants): Placebo-Buprenorphine Low | EXPERIMENTAL | Three treatment periods consisting of 3 days each of investigational treatment * 1=placebo + fentanyl, * 2=low dose buprenorphine + fentanyl, * 3 (optional)=low dose buprenorphine only Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.075, 0.15, 0.25 and 0.35 mg/70 kg. Each dosing period was followed by 10-17 days of washout. |
| Part A (Healthy Participants): Placebo-Buprenorphine High | EXPERIMENTAL | Three treatment periods consisting of 3 days each of investigational treatment * 1=placebo + fentanyl, * 2=high dose buprenorphine + fentanyl, * 3 (optional)=high dose buprenorphine only Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.075, 0.15, 0.25 and 0.35 mg/70 kg. Each dosing period was followed by 10-17 days of washout. |
| Part A (Healthy Participants): Buprenorphine Low-Placebo | EXPERIMENTAL | Three treatment periods consisting of 3 days each of investigational treatment * 1=low dose buprenorphine + fentanyl, * 2=placebo + fentanyl, * 3 (optional)=low dose buprenorphine only Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.075, 0.15, 0.25 and 0.35 mg/70 kg. Each dosing period was followed by 10-17 days of washout. |
| Part A (Healthy Participants): Buprenorphine High-Placebo | EXPERIMENTAL | Three treatment periods consisting of 3 days each of investigational treatment * 1=high dose buprenorphine + fentanyl, * 2=placebo + fentanyl, * 3 (optional)=high dose buprenorphine only Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.075, 0.15, 0.25 and 0.35 mg/70 kg. Each dosing period was followed by 10-17 days of washout. |
| Part B (Opioid-Tolerant): Placebo-Buprenorphine Low | EXPERIMENTAL | Opioid-tolerant participants in Part B undergo a washout of their own opioids during which these were replaced with oral oxycodone, and continue at stable doses of oxycodone from at least 48 hours before Period 1 to the end of Period 2. Two treatment periods: * 1=placebo (Day 1), * 2=low dose buprenorphine + fentanyl (Day 3) Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.25, 0.35, 0.5 and 0.7 mg/70 kg. |
| Part B (Opioid-Tolerant): Placebo-Buprenorphine Mid | EXPERIMENTAL | Opioid-tolerant participants in Part B undergo a washout of their own opioids during which these were replaced with oral oxycodone, and continue at stable doses of oxycodone from at least 48 hours before Period 1 to the end of Period 2. Two treatment periods: * 1=placebo (Day 1), * 2=mid dose buprenorphine + fentanyl (Day 3) Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.25, 0.35, 0.5 and 0.7 mg/70 kg. |
| Part B (Opioid-Tolerant): Placebo-Buprenorphine High | EXPERIMENTAL | Opioid-tolerant participants in Part B undergo a washout of their own opioids during which these were replaced with oral oxycodone, and continue at stable doses of oxycodone from at least 48 hours before Period 1 to the end of Period 2. Two treatment periods: * 1=placebo (Day 1), * 2=high dose buprenorphine + fentanyl (Day 3) Fentanyl was administered as a bolus over 90 seconds in escalating doses of 0.25, 0.35, 0.5 and 0.7 mg/70 kg. |
| Name | Type | Description |
|---|---|---|
| Buprenorphine Injectable Solution - Part A | DRUG | 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. |
| Placebo - Parts A + B | DRUG | 0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration. |
| Fentanyl - Part A | DRUG | 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. |
| Ondansetron - Parts A + B | DRUG | 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. |
| Buprenorphine Injectable Solution - Part B | DRUG | 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. |
| Fentanyl - Part B | DRUG | 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. |
| Oxycodone - Part B | DRUG | 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. |
Inclusion Criteria: * Part A-Healthy Subjects: 1. Signed the informed consent form (ICF) and able to comply with study requirements and restrictions 2. Age 18- 45, inclusive years for this part 3. Women of childbearing potential must have a negative serum pregnancy test prior to enrolment an...
Buprenorphine Injectable - Part A is an investigational injectable buprenorphine solution developed by Supernus Pharmaceuticals, Inc. It is being studied in the opioid use setting and is a small molecule formulation. It is also known as Buprenorphine Injectable Solution - Part A.
Buprenorphine Injectable - Part A targets OPRM1 and OPRK1, the mu and kappa opioid receptors, and acts as an agonist at these receptors. Both targets are opioid receptors, which places the compound in the opioid agonist class of small molecules.
Buprenorphine Injectable - Part A is developed by Supernus Pharmaceuticals, Inc., which trades under the ticker SUPN. The company is the sponsor behind the injectable buprenorphine solution program.
Buprenorphine Injectable - Part A is in Phase 1 clinical development. It is investigational and has not been approved by the FDA. One Phase 1 trial has been completed, and no trials are currently active.
Buprenorphine Injectable - Part A has been studied in NCT03747341, a completed Phase 1 trial titled Buprenorphine-Fentanyl Interaction Study. The trial enrolled 22 participants in the Netherlands, included healthy volunteers, was randomized and controlled, and enrolled adults 18 years and older of all sexes.
Yes, Buprenorphine Injectable - Part A is also known as Buprenorphine Injectable Solution - Part A. Both names refer to the same investigational injectable buprenorphine product from Supernus Pharmaceuticals, Inc. being studied in the opioid use setting.