Study: NCT03747341

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo - Parts A + B
Description: 0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo - Parts A + B
Description: 0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo - Parts A + B
Description: 0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo - Parts A + B
Description: 0.9% normal saline for IV administration was used as placebo matching the buprenorphine formulation and administration.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part A
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part A
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part A
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part A
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ondansetron - Parts A + B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Buprenorphine Injectable Solution - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Buprenorphine Injectable Solution - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Buprenorphine Injectable Solution - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Fentanyl - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Oxycodone - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Oxycodone - Part B
Description: 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.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Oxycodone - Part B
Description: 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.