A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)

NCT01396005 | Completed Phase 1 Results

• 1 other identifier: P08123
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this study, participants on methadone or buprenorphine/naloxone maintenance therapy will be given boceprevir. Blood samples will be taken at specified intervals to find out whether boceprevir affects the pharmacokinetics of methadone, buprenorphine, or naloxone.

Conditions

Hepatitis C Virus

Outcome Measures

Primary Outcomes (4)

• Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir

  AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.

  Methadone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and methadone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

• Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir

  Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for methadone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for methadone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for methadone + boceprevir.

  Methadone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and methadone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

• AUC of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir

  AUC is a measure of the amount of drug in the blood over time, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.

  Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

• Cmax of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir

  Cmax is a measure of the maximum level of drug in the blood, measured at steady state (time at which the amount of drug eliminated by the body is in equilibrium with the amount taken in). The Day 1, 0 through 24 hour samples were for buprenorphine/naloxone levels in the absence of boceprevir co-administration. The Day 7, 0 through 24 hour samples were for buprenorphine/naloxone levels in the presence of boceprevir co-administration. The Day 5 and 6 predose samples were to check steady state for buprenorphine/naloxone + boceprevir.

  Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

Secondary Outcomes (2)

• AUC of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir

  Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

• Cmax of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir

  Buprenorphine/naloxone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and buprenorphine/naloxone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6.

Study Arms (2)

Methadone + boceprevir

EXPERIMENTAL

Participants receive standard methadone maintenance therapy (20-150 mg tablets, liquid, or disket, orally, once per day) on Days 1 through 8 + boceprevir (800 mg \[4 x 200 mg capsules\], orally, every 8 hours) on Days 2 through 7)

Drug: boceprevir; Drug: methadone

Buprenorphine/naloxone + boceprevir

EXPERIMENTAL

Participants receive standard buprenorphine/naloxone maintenance therapy (8/2-24/6 mg, tablets, sublingual, once per day) on Days 1 through 8 + boceprevir (800 mg \[4 x 200 mg capsules\], orally, every 8 hours) on Days 2 through 7

Drug: boceprevir; Drug: buprenorphine/naloxone

Interventions

boceprevir DRUG

boceprevir 800 mg (4 x 200 mg capsules), orally, every 8 hours, Day 2 through Day 7

Also known as: SCH 503034, Victrelis™

Buprenorphine/naloxone + boceprevir; Methadone + boceprevir

methadone DRUG

methadone, 20-150 mg tablets, liquid, or disket, orally, once per day, Day 1 through Day 8

Methadone + boceprevir

buprenorphine/naloxone DRUG

buprenorphine/naloxone 8/2-24/6 mg, tablets, sublingual, once per day, Day 1 through Day 8

Buprenorphine/naloxone + boceprevir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body Mass Index (BMI) between 18 and 36, inclusive
• Reliable participation in a methadone maintenance or buprenorphine maintenance or buprenorphine/naloxone maintenance program for at least two (2) months prior to Day 1.
• Is receiving once daily oral dose of methadone therapy at a stable
• individualized dose for at least 4 weeks, receiving once
• daily buprenorphine dose at a stable individualized dose for at 4 weeks with, if on buprenorphine only therapy, naloxone added for at least 2 weeks prior to Day 1.
• lead electrocardiogram (ECG) conduction intervals within gender-specific normal range
• Vital signs within normal range
• Clinical laboratory tests within normal range
• Women who are postmenopausal, surgically sterilized, or premenopausal and use a medically-accepted method of contraception.

You may not qualify if:

• Pregnancy, breast feeding, or intention to become pregnant or father a child while on study or within 3 months after end of trial
• History or presence of inflammatory bowel disease, ulcers, or gastrointestinal or rectal bleeding
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• History of pancreatic injury or pancreatitis
• History or presence of liver disease or liver injury
• History or presence of impaired renal function
• History of urinary obstruction or difficulty in voiding
• History of any infectious disease within 4 weeks prior to drug administration that in the opinion of the investigator, affects the subject's ability to participate in the trial
• Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
• Positive screen for drugs with a high potential for abuse such as cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, or opiates/opioids
• Excessive use of alcohol in the 2 weeks prior to Day -1, defined as greater than 3 glasses of alcoholic beverages (1 is approximately equivalent to: beer \[284 mL/10 oz\], wine
• \[125 mL/4 oz\], or distilled spirits \[25 mL/1 oz\]) per day.
• Blood donation in the past 60 days
• Previous administration of SCH 503034 (boceprevir)
• Current participation in another clinical study or participation in a clinical study (e.g., laboratory or clinical evaluation) within 30 days of baseline

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Hulskotte EG, Bruce RD, Feng HP, Webster LR, Xuan F, Lin WH, O'Mara E, Wagner JA, Butterton JR. Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy. Eur J Clin Pharmacol. 2015 Mar;71(3):303-11. doi: 10.1007/s00228-014-1789-4. Epub 2015 Feb 11.

  PMID: 25666027 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; Methadone; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6327

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: July 18, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: April 7, 2017
• Results First Posted: March 11, 2013

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share