The Effects of the Direct Acting Antiviral Agent Boceprevir on the Pharmacokinetics of Maraviroc in Healthy Volunteers

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor:
Collaborators:
Université de Montréal
McGill University Health Center
Toronto General Hospital
Information provided by (Responsible Party):
Nancy Sheehan, Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT01627717
First received: June 21, 2012
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

Infection by both HIV and hepatitis C virus (HCV)is frequent due to similar transmission modes. Near 20% of people living with HIV are also infected by HCV. People living with HIV are treated by anti-HIV medications that may interact with numerous other medications, including new medications against HCV.

Boceprevir is one of these new HCV medications and it is now considered as part of the standard of care for people infected with HCV. Previous research has shown boceprevir may influence the capacity of the liver to breakdown (metabolize) certain medications and when these medications are used in combination with boceprevir, their blood concentrations may be increased or decreased which could increase the risk of side effects or decrease efficacy. Among the drugs having a potential for an interaction with boceprevir is maraviroc, an anti-HIV medication. If concentrations of maraviroc increase, people may experience more side effects. However, if concentrations of maraviroc decrease, people living with HIV may have a lower suppression of the virus. This could increase the risk for the HIV virus to develop resistance, that is that the treatment will no longer be effective. No studies have been conducted to investigate the effects of boceprevir on blood concentrations of maraviroc. This research project addresses this research question. This project, however, cannot be done with people living with HIV since resistance may develop in these people if the concentrations of maraviroc decrease. It is for this reason that the investigators wish to recruit healthy people not infected with HIV nor HCV.

Eleven healthy volunteers will be included. They will receive maraviroc 150 mg (1 tablet) every 12 hours from days 1 to 19 inclusively. On day 5, a total of ten blood samples will be drawn during the following 12 hours (at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours after maraviroc morning dose intake) to measure the blood concentrations of maraviroc. Boceprevir 800 mg (4 capsules) every 8 hours with food will be started on day 6 and continued until day 19 inclusively. On day 19, after the morning maraviroc and boceprevir dose, another ten blood samples will be drawn over a 12 hour period. A phone follow-up will be done on day 26. Thus, the total study duration for subjects is 26 days. The investigators will compare the blood concentrations of maraviroc when given alone to the blood concentrations of maraviroc when given with boceprevir.


Condition Intervention Phase
Healthy
Drug: Maraviroc (5 days)
Drug: Maraviroc and boceprevir (14 days)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effects of the Direct Acting Antiviral Agent Boceprevir on the Pharmacokinetics of Maraviroc in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • Change in maraviroc AUC [ Time Frame: Day 19 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in maraviroc Tmax [ Time Frame: Day 19 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: Up to day 26 ] [ Designated as safety issue: Yes ]
    Adverse events will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (2004).

  • Change in maraviroc Cmax [ Time Frame: Day 19 ] [ Designated as safety issue: No ]
  • Change in maraviroc Cmin [ Time Frame: Day 19 ] [ Designated as safety issue: No ]
  • Change in maraviroc Cl/F [ Time Frame: Day 19 ] [ Designated as safety issue: No ]
  • Change in maraviroc Vd [ Time Frame: Day 19 ] [ Designated as safety issue: No ]
  • Change in maraviroc T1/2 [ Time Frame: Day 19 ] [ Designated as safety issue: No ]

Estimated Enrollment: 11
Study Start Date: June 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Maraviroc Boceprevir Drug: Maraviroc (5 days)
Subjects will receive maraviroc 150 mg tablets (1 tablet) every 12 hours from days 1 to 5 inclusively.
Other Name: Celsentri (DIN #: 02299844) CAS# 376348-65-1
Drug: Maraviroc and boceprevir (14 days)
From days 6 to 19, inclusively, boceprevir 800 mg (4 capsules of 200 mg) every 8 hours with food will be given with maraviroc 150 mg (1 tablet of 150 mg) every 12 hours.
Other Names:
  • Celsentri (DIN #: 02299844) CAS# 376348-65-1
  • Victrelis (DIN#:02370816) CAS# 394730-60-0

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Caucasian males
  • healthy individuals based on history/physical examination and laboratory evaluations (no out-of-range results from hematology tests (hemoglobin (Hb) > 130 g/L in men; absolute neutrophil count (ANC) > 2000 cells/uL; platelets > 159 x 109/L), biochemistry (AST < 35 IU/L, ALT < 40, IU/L, alkaline phosphatase < 100 IU/L, total bilirubin < 17 umol/L, lipase < 45 IU/L, creatinine < 120 umol/L, normal coagulation tests (INR < 1.2, aPPT < 40 seconds) and urinalysis.
  • LDL-cholesterol </= 5 mmol/L, triglycerides </= 1.7 mmol/L and a 10 year estimate of cardiovascular (CV) disease risk of </= 10% ("low risk") as per the Framingham risk score modified for family history (doubling of CV risk if any CV disease in a first-degree relative before 60 years of age); the modified Framingham risk score takes into account age, HDL-cholesterol, total cholesterol, systolic blood pressure, smoker status, presence of diabetes and family history of CV disease
  • normal 12-lead electrocardiogram
  • systolic blood pressure between 105 and 130 mmHg
  • diastolic blood pressure between 60 and 90 mmHg
  • supine heart rate between 60 and 100 beats per minutes
  • no evidence of HIV infection (ELISA test and Western Blot), no evidence of hepatitis B virus infection (HBsAg negative and anti-HBcAg negative or HBsAg negative with positive anti-HBsAg and positive anti-HBcAg) or HCV infection at screening (anti-HCV serology)
  • using an effective barrier method of contraception
  • non-smoker
  • drinking less than 14 units of alcohol per week with a maximum of 4 units per day where one unit of alcohol corresponds to 341 mL of standard beer or 142 mL of wine or 43 ml of spirits
  • negative illicit drug test at screening;
  • with a body mass index between 18.0 to 30.0 kg/m2
  • aged from 18 to 50 years old
  • volunteers must be able to understand and comply with the protocol requirements and willing to sign the informed consent form prior to any study procedure;
  • absence of exclusion criteria.

Exclusion Criteria:

  • history of postural hypotension
  • cardiac disease
  • acute or chronic liver disease or any hepatic impairment
  • acute or chronic kidney disease or any renal impairment
  • use of prescription drugs, over the counter drugs, recreational drugs, herbal or dietary supplements including vitamins and grapefruit juice within 15 days of study initiation (day 1) except for acetaminophen and/or ibuprofen on an as needed basis. These products will also be prohibited during the study (except for as needed acetaminophen and/or ibuprofen)
  • subjects who received any experimental medication within the last 2 months and/or donated blood during the previous 2 months or intends to donate blood within 2 months following completion of the study will also be excluded;
  • subjects who had unprotected sexual activities during the last 6 months with a new or recent partner
  • subjects who injected intravenous drugs over the last 6 months
  • subjects with a social condition, psychological or addictive disorder that would impair protocol adherence.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627717

Contacts
Contact: Nancy L Sheehan, B.Pharm, MSc 514-343-6111 ext 0884 nancy.sheehan@umontreal.ca
Contact: Dominic Martel, B.Pharm, MSc 514-406-5117 Dominic.Martel@uhn.ca

Locations
Canada, Quebec
Centre Hospitalier de l'Université de Montréal Recruiting
Montréal, Quebec, Canada, H2W 1T8
Contact: Cécile Tremblay, MD    514-890-8148    c.tremblay@umontreal.ca   
Principal Investigator: Cecile Tremblay, MD         
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Université de Montréal
McGill University Health Center
Toronto General Hospital
Investigators
Principal Investigator: Cecile Tremblay, MD Centre Hospitalier de l'Université de Montréal
Principal Investigator: Line Labbé, PhD Faculté de pharmacie, Université de Montréal
Principal Investigator: Nancy L Sheehan, B.Pharm, MSc Faculté de pharmacie, Université de Montréal
Study Director: Alice Tseng, PharmD Toronto General Hospital
  More Information

No publications provided

Responsible Party: Nancy Sheehan, Associate Clinical Professor, Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT01627717     History of Changes
Other Study ID Numbers: MVC.1201
Study First Received: June 21, 2012
Last Updated: May 30, 2013
Health Authority: Canada: Health Canada

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
maraviroc
boceprevir
HIV
HCV
drug interaction
pharmacokinetics

Additional relevant MeSH terms:
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014