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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01396005
First received: June 28, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C Virus
Drug: boceprevir
Drug: methadone
Drug: buprenorphine/naloxone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, One-Period Study in Patients Receiving Methadone or Buprenorphine/Naloxone Maintenance Therapy to Evaluate the Effect of SCH 503034 (Boceprevir) on Either Methadone or Buprenorphine/Naloxone Plasma Concentrations (Protocol No. P08123)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Maximum Concentration (Cmax) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • AUC of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Cmax of Buprenorphine (Administered in Combination With Naloxone) at Steady State With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • AUC of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Cmax of Naloxone (Administered in Combination With Buprenorphine) at Steady State With or Without Boceprevir [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 21
Study Start Date: September 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methadone + boceprevir
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
boceprevir 800 mg (4 x 200 mg capsules), orally, every 8 hours, Day 2 through Day 7
Other Name: SCH 503034, Victrelis™
Drug: methadone
methadone, 20-150 mg tablets, liquid, or disket, orally, once per day, Day 1 through Day 8
Experimental: Buprenorphine/naloxone + boceprevir
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
boceprevir 800 mg (4 x 200 mg capsules), orally, every 8 hours, Day 2 through Day 7
Other Name: SCH 503034, Victrelis™
Drug: buprenorphine/naloxone
buprenorphine/naloxone 8/2-24/6 mg, tablets, sublingual, once per day, Day 1 through Day 8

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

  • 12-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.

Exclusion Criteria:

  • 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
  • Study staff personnel or family members of the study staff personnel
  • Demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) that, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial
  • History of malignancy within 5 years from Screening
  • Consumption of excessive amounts (equivalent to > 6 cups of brewed coffee/day) of coffee, tea, cola or other caffeinated beverages
  • Receipt of any of the following more recently than the washout period prior to Baseline: inhibitors or inducers of cytochrome (CYP) P450, CYP2B6, CYP3A4, and CYP2D6; or oral contraceptives containing drospirenone
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01396005     History of Changes
Other Study ID Numbers: P08123
Study First Received: June 28, 2011
Results First Received: December 6, 2012
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Buprenorphine
Methadone
Naloxone
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotic Antagonists
Narcotics
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 23, 2014