Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ondansetron- Parts A+ B · 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...
Ondansetron- Parts A+ B is an investigational small molecule being studied in healthy volunteers for pain-related research. It is currently in Phase 1 clinical development by Indivior Pharmaceuticals, Inc. The drug is being evaluated in a controlled study involving healthy participants to assess its effects.
Ondansetron- Parts A+ B is being developed by Indivior Pharmaceuticals, Inc., a company listed on the stock exchange under the ticker INDV. The company is conducting clinical research on this investigational small molecule in the therapeutic area of pain.
Ondansetron- Parts A+ B is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities and is still undergoing clinical trials to evaluate its safety and effects in healthy volunteers.
Ondansetron- Parts A+ B has been studied in one clinical trial with the identifier NCT03747341, titled "Buprenorphine-Fentanyl Interaction Study." This Phase 1 trial was completed and enrolled 22 participants in the Netherlands. The study was randomized and controlled, involving healthy volunteers aged 18 years and older.
Ondansetron- Parts A+ B is a drug name used in clinical research, but it is not stated to be the same as the marketed medication ondansetron. The drug is being investigated by Indivior Pharmaceuticals for pain-related research, and its specific composition or relationship to other ondansetron products is not disclosed.