Buprenorphine-Fentanyl Interaction Study

NCT ID: NCT03747341

Last Updated: 2025-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-22

Study Completion Date

2019-01-04

Brief Summary

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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.

Detailed Description

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The study will be performed in 2 parts. Part A is a 3-period study; the first 2 periods have a single-blind, placebo-controlled, cross-over design, where subjects will be randomized in a 1:1 ratio to 2 treatment sequences determined by the order in which they receive buprenorphine or matching placebo. Period 3 is an open-label design where the same subjects will receive buprenorphine only. This period is optional, and will include approximately 6 subjects.

Part B is an open-label study in opioid tolerant patients. All will receive placebo plus fentanyl in Period 1 to permit dose escalation to full respiratory effects of fentanyl before assessing the interaction with buprenorphine. Subjects will receive buprenorphine plus fentanyl during Period 2 to assess the interaction with buprenorphine.

To study ventilation, the dynamic end-tidal forcing technique will be used. This technique enables the Investigator to force end-tidal partial pressure of carbon dioxide and end-tidal partial pressure of oxygen to follow a specific pattern in time. Subjects with a procedure-related adverse event (AE) will be treated according to established ventilatory support and opioid reversal protocols.

Conditions

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Healthy Opioid Use

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Part A is a 3 period study in approximately 18 healthy subjects. Subjects will be randomized in a 1:1 ratio to 2 treatment sequences determined by the order in which they receive buprenorphine or placebo (periods 1 and 2). An optional open-label Period 3 may be conducted in which subjects will receive buprenorphine only.

Part B is an open label study of approximately 8 opioid tolerant patients. All will undergo a washout of their own opioids which will be replaced with oral oxycodone and continue at stable doses from at least 48 hours prior to Period 1 to the end of Period 2. All will receive placebo plus fentanyl during Period 1 and buprenorphine plus fentanyl during Period 2.
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants
Participants will be blinded to treatment with buprenorphine or placebo during Periods 1 and 2 in Part A only.

Study Groups

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Part A (Healthy Participants): Placebo-Buprenorphine Low

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.

Group Type EXPERIMENTAL

Buprenorphine Injectable Solution - Part A

Intervention Type 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

Intervention Type DRUG

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

Fentanyl - Part A

Intervention Type 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

Intervention Type 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.

Part A (Healthy Participants): Placebo-Buprenorphine High

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.

Group Type EXPERIMENTAL

Buprenorphine Injectable Solution - Part A

Intervention Type 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

Intervention Type DRUG

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

Fentanyl - Part A

Intervention Type 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

Intervention Type 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.

Part A (Healthy Participants): Buprenorphine Low-Placebo

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.

Group Type EXPERIMENTAL

Buprenorphine Injectable Solution - Part A

Intervention Type 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

Intervention Type DRUG

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

Fentanyl - Part A

Intervention Type 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

Intervention Type 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.

Part A (Healthy Participants): Buprenorphine High-Placebo

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.

Group Type EXPERIMENTAL

Buprenorphine Injectable Solution - Part A

Intervention Type 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

Intervention Type DRUG

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

Fentanyl - Part A

Intervention Type 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

Intervention Type 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.

Part B (Opioid-Tolerant): Placebo-Buprenorphine Low

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.

Group Type EXPERIMENTAL

Placebo - Parts A + B

Intervention Type DRUG

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

Ondansetron - Parts A + B

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Part B (Opioid-Tolerant): Placebo-Buprenorphine Mid

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.

Group Type EXPERIMENTAL

Placebo - Parts A + B

Intervention Type DRUG

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

Ondansetron - Parts A + B

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Part B (Opioid-Tolerant): Placebo-Buprenorphine High

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.

Group Type EXPERIMENTAL

Placebo - Parts A + B

Intervention Type DRUG

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

Ondansetron - Parts A + B

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Placebo - Parts A + B

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

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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TEMGESIC® TEMGESIC®

Eligibility Criteria

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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 and must agree to use a medically acceptable means of contraception through at least 3 months after last dose of study drug
4. Body Mass Index (BMI) 18-30 kg/m\^2, inclusive
5. Healthy as defined by the Investigator
6. No history of substance use disorder
7. No current use of any central nervous system (CNS) depressants
* Part B-Opioid-tolerant patients

1. Signed the ICF and able to comply with study requirements and restrictions
2. Age 18 - 55 years inclusive
3. Same as #3 above
4. BMI 18-32 kg/m\^2
5. Opioid tolerant patients administered opioids at daily doses greater than or equal to 90 mg oral morphine equivalents
6. Stable as defined by the Investigator
7. No current use of any CNS depressants, besides opioids, for 5 half-lives of the product before first study drug administration

Exclusion Criteria

Part A

1. History of risk factors of Torsades de Pointes or an electrocardiogram (ECG) demonstrating a Fridericia's corrected QT interval (QTcF) \> 450 msec in males and QTcF \> 470 msec in females at screening;
2. Currently meet the criteria for diagnosis of substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria on any substance;
3. Any other active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
4. Current smokers and those who have smoked within the last 6 months;
5. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months;
6. Consume, on average, \> 20 units/week of alcohol in men and \> 13 units/week of alcohol in women; (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
7. Previous treatment with any prescribed medications (including all types of vaccines) or over-the-counter (OTC) medications within 14 days or 5 half-lives (whichever is longer) prior to first study treatment administration;
8. Previous or current treatment with opioid agonist, partial agonist, or antagonist treatment within 30 days prior to the first study drug administration;
9. Require ongoing prescription or OTC medications that are clinically relevant cytochrome (CYP) P450 3A4 or CYP P450 2C8 inducers or inhibitors;
10. Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent;
11. History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
12. Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg prior to Day 1;
13. History or presence of allergic response to buprenorphine or fentanyl;
14. Subjects who have demonstrated allergic reactions which, in the opinion of the Investigator and sponsor, interfere with their ability to participate in the trial;
15. Estimated glomerular filtration rate \<60 mL/min as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation;
16. Anaemia at screening or donation of \> 250 mL of blood or plasma within the last 3 months;
17. Positive serology tests for human immunodeficiency virus (HIV), hepatitis B (HBsAg), or hepatitis C (HepC);
18. Aspartate transaminase (AST) or alanine transaminase (ALT) levels \>1.5 times the upper limit of normal at screening;
19. Treatment with another investigational drug within 3 months prior to dosing or having participated in more than 4 investigational drug studies within 1 year prior to screening;
20. Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study.

Part B

1. Same as Part A #1
2. Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than opioids, caffeine or nicotine;
3. Same as Part A #3;
4. Smoking of \>10 cigarettes/day or equivalent and not able to abstain from smoking cigarettes during each dose administration day;
5. Consume, on average, \>27 units/week of alcohol in men and \>20 units/week of alcohol in women;
6. Use of buprenorphine within 10 days of the first study drug administration;
7. Require ongoing prescription or OTC medications that are clinically relevant CYP P450 3A4 or CYP P450 2C8 inducers or inhibitors;
8. Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent;
9. History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
10. Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg prior to Day 1;
11. History or presence of allergic response to buprenorphine or fentanyl;
12. Opioid-tolerant patients who have demonstrated allergic reactions which, in the opinion of the Investigator and sponsor, interfere with their ability to participate in the trial;
13. Same as Part A #15
14. Same as Part A #16
15. Same as Part A #17
16. Same as Part A #18
17. Same as Part A #19
18. Same as Part A #20
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Indivior Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geert J Groeneveld

Role: PRINCIPAL_INVESTIGATOR

Center for Human Drug Research

Locations

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Center for Human Drug Research

Leiden, The Netherlands, Netherlands

Site Status

Countries

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Netherlands

References

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Olofsen E, Algera MH, Moss L, Dobbins RL, Groeneveld GJ, van Velzen M, Niesters M, Dahan A, Laffont CM. Modeling buprenorphine reduction of fentanyl-induced respiratory depression. JCI Insight. 2022 May 9;7(9):e156973. doi: 10.1172/jci.insight.156973.

Reference Type BACKGROUND
PMID: 35316224 (View on PubMed)

Moss LM, Algera MH, Dobbins R, Gray F, Strafford S, Heath A, van Velzen M, Heuberger JAAC, Niesters M, Olofsen E, Laffont CM, Dahan A, Groeneveld GJ. Effect of sustained high buprenorphine plasma concentrations on fentanyl-induced respiratory depression: A placebo-controlled crossover study in healthy volunteers and opioid-tolerant patients. PLoS One. 2022 Jan 27;17(1):e0256752. doi: 10.1371/journal.pone.0256752. eCollection 2022.

Reference Type RESULT
PMID: 35085249 (View on PubMed)

Other Identifiers

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2017-004858-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHDR1754

Identifier Type: OTHER

Identifier Source: secondary_id

INDV-6000-101

Identifier Type: -

Identifier Source: org_study_id

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