A Drug Interaction Study of Boceprevir in Combination With Amlodipine or Diltiazem in Healthy Volunteers

A Drug Interaction Study Investigating the Effect of Boceprevir on the Pharmacokinetics of the Calcium Channel Blockers Amlodipine and Diltiazem and Vice Versa in Healthy Volunteers

The purpose of this study is to evaluate the pharmacokinetic interactions between the hepatitis C NS3 protease inhibitor boceprevir and the calcium channel blockers amlodipine and diltiazem in healthy volunteers.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension; Hepatitis C
• Intervention / Treatment: Drug: Amlodipine; Drug: Diltiazem

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Clinical Investigation Unit, Ottawa Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to sign informed consent prior to any study-related activities.
2. Male or female subjects between 18 and 65 years of age inclusive.
3. Healthy, i.e. not suffering from a relevant acute or chronic illness.
4. Body Mass Index (BMI) of 17.5 to 31 kg/m2; and a total body weight > 50 kg (110 lbs).
5. Acceptable medical history, physical examination, and 12-lead ECG at screening.
6. Acceptable laboratory values that indicate adequate baseline organ function at screening visit.
7. Willing to stop using any herbal or natural health products for 2 weeks prior to and during the study including: Grapefruit, grapefruit juice, St. John's Wort.
8. Willingness to abstain from alcohol use for 3 days prior to and during the study.

9. Female subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control:

   • Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD)
   • A vasectomized partner
   • Total abstinence from sexual intercourse

Exclusion Criteria:

1. Have serological evidence of exposure to HIV or HCV.
2. Known allergies to any of the study medications.

3. Female subjects of childbearing potential who:

   • Has a positive urine pregnancy test at screening.
   • Is not willing to use a reliable method of barrier contraception during the study.
   • Using only oral contraceptive as a birth control method.
   • Is breastfeeding.
4. Inability to adhere to protocol.
5. Use of any medications (2 weeks prior to or during the study) other than occasional use of acetaminophen.
6. Female subjects using contraceptives that contain drospirenone.
7. Subjects that are currently smoking.
8. Subjects with hypertension or heart disease requiring medical treatment.
9. Any condition possibly affecting drug absorption (e.g., gastro intestinal disorder).
10. Patients may be excluded from the study for other reasons, at the investigator's discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: boceprevir; boceprevir 800 mg tid	Drug: Amlodipine; amlodipine 2.5 mg QD; Drug: Diltiazem; diltiazem 120 mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetics	AUC, Cmax, Cmin	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants with adverse events	description and frequency of adverse events for all participants during the study	29 days

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Charles la Porte, PharmD, PhD, Ottawa Hospital Research Institute

Publications and helpful links

Helpful Links

• Info on Clinical Investigation Unit

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ANTICIPATED): September 1, 2012

Study Registration Dates

• First Submitted: March 1, 2012
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (ESTIMATE): March 9, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: hypertension; pharmacokinetics; HCV; amlodipine; boceprevir; diltiazem
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hypertension; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine; Diltiazem
• Other Study ID Numbers: OHRI-BCP-CCB-2012