A Drug Interaction Study Investigating the Effect of Rifabutin on the Pharmacokinetics of Maraviroc (RIFAMARA)

Healthy volunteers are being recruited for this pharmacokinetics study. The objective is to characterize the pharmacokinetic properties of maraviroc alone and when administered with rifabutin and to assess rifabutin and 25-O-desacetyl-rifabutin pharmacokinetics compared to the literature.

Study Overview

• Status: Completed
• Conditions: HIV Infection; HIV-1 Infection; Mycobacterium Avium Complex (MAC)
• Intervention / Treatment: Drug: Rifabutin; Drug: Maraviroc

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital -General Campus

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:

• Able and willing to sign informed consent prior to any study-related activities.
• Male or female participants between 18 and 65 years of age inclusive.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Healthy, i.e. not suffering from an acute or chronic illness and not using medications.
• Acceptable medical history, physical examination, and 12-lead ECG at screening.
• Acceptable laboratory values that indicate adequate baseline organ function at screening visit.
• 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.
• Willingness to abstain from alcohol use for 3 days prior to and during the study.
• Participant must practice a reliable method of birth control while they are participating in the study; for instance an intrauterine device (IUD), condom with spermicidal gel or foam, diaphragm with spermicidal gel or foam, vasectomy, tubal ligation, hysterectomy or abstinence or female must be post menopausal for at least one year.

Exclusion Criteria:

• Have serological evidence of exposure to HIV
• Female patients of childbearing potential who has a positive urine pregnancy test at screening
• Participants not willing to use a reliable method of barrier contraception during the study.
• Is breastfeeding.
• Inability to adhere to protocol.
• Use of any medications (2 weeks prior to or during the study) other than occasional use of acetaminophen.
• Participants taking oral contraceptive medications.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• 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: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Maraviroc; Two period pharmacokinetic drug-drug interaction Period one -Maraviroc alone; Period two -Maraviroc and Rifabutin Substance: Maraviroc (Celsentri, MVC) tablets, 300 mg; dose: oral, 300 mg (1 tablet) twice daily Substance: Rifabutin (mycobutin, RFB) capsules, 150 mg; dose: oral, 300 mg (2 capsules) once daily	Drug: Rifabutin; Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days; Other Names: Mycobutin, RFB; Drug: Maraviroc; Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days; Other Names: Celsentri, MVC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24	Maraviroc pharmacokinetics: Maraviroc only AUC (h*μg/L), Maraviroc + Rifabutin AUC (h*μg/L), Rifabutin AUC (h*μg/L), 25-O-desacetyl rifabutin AUC (h*μg/L).	Maraviroc: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 hour. Rifabutin: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hour..
Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma.	Maraviroc + Rifabutin pharmacokinetics: Maraviroc only Cmax (μg/L), Maraviroc only C12 (μg/L), Maraviroc + Rifabutin Cmax (μg/L), Maraviroc + Rifabutin C12 (μg/L), Rifabutin Cmax (μg/L), Rifabutin C24 (μg/L), 25-O-desacetyl rifabutin Cmax (μg/L), 25-O-desacetyl rifabutin C24 (μg/L).	Maraviroc: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 hour. Rifabutin: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hour..

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Tolerability of the Treatments	description and frequency of adverse events for all participants during the study.	30 days

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Pfizer
• Investigators: Principal Investigator: Donald W Cameron, MD, The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa

Publications and helpful links

General Publications

• Ghannad M, Dennehy M, la Porte C, Seguin I, Tardiff D, Mallick R, Sabri E, Zhang G, Kanji S, Cameron DW. A drug interaction study investigating the effect of Rifabutin on the pharmacokinetics of Maraviroc in healthy subjects. PLoS One. 2019 Oct 24;14(10):e0223969. doi: 10.1371/journal.pone.0223969. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: June 19, 2013
• First Submitted That Met QC Criteria: July 3, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: healthy volunteers
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Infections; Communicable Diseases; Mycobacterium avium-intracellulare Infection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc; Rifabutin
• Other Study ID Numbers: 2013 0080-01H