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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C Virus

Treatments: Drug: boceprevir; Drug: methadone; Drug: buprenorphine/naloxone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01396005

P08123

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups

Methadone + boceprevir

Experimental group

Description:

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)

Treatment:

Drug: methadone

Drug: boceprevir

Buprenorphine/naloxone + boceprevir

Experimental group

Description:

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

Treatment:

Drug: buprenorphine/naloxone

Drug: boceprevir