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

• ClinicalTrials.gov Identifier: NCT01894776
• Recruitment Status: Completed
• First Posted: July 10, 2013
• Results First Posted: March 10, 2020
• Last Update Posted: March 10, 2020
• Sponsor: Ottawa Hospital Research Institute
• Collaborator: Pfizer
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Tracking Information

• First Submitted Date: June 19, 2013
• First Posted Date: July 10, 2013
• Results First Submitted Date: December 20, 2019
• Results First Posted Date: March 10, 2020
• Last Update Posted Date: March 10, 2020
• Study Start Date: June 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2020)

• Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 [ Time Frame: 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 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 and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. [ Time Frame: 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 + 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).

Original Primary Outcome Measures (submitted: July 3, 2013)

pharmacokinetics [ Time Frame: 15 days ]

Maraviroc pharmacokinetics AUC, Cmax and C12 with and without rifabutin Rifabutin and 25-O-desacetyl-rifabutin AUC, Cmax and C24

Current Secondary Outcome Measures (submitted: July 3, 2013)

Safety/Tolerability of the Treatments [ Time Frame: 30 days ]

description and frequency of adverse events for all participants during the study.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Drug Interaction Study Investigating the Effect of Rifabutin on the Pharmacokinetics of Maraviroc
• Official Title: A Drug Interaction Study Investigating the Effect of Rifabutin on the Pharmacokinetics of Maraviroc
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• HIV Infection
• HIV-1 Infection
• Mycobacterium Avium Complex (MAC)

Intervention

• Drug: Rifabutin
  Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days
  Other Name: Mycobutin, RFB
• Drug: Maraviroc
  Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
  Other Name: Celsentri, MVC

Study Arms

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

Interventions:

• Drug: Rifabutin
• Drug: Maraviroc

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2015): 15
• Original Estimated Enrollment (submitted: July 3, 2013): 14
• Actual Study Completion Date: February 2015
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01894776
• Other Study ID Numbers: 2013 0080-01H
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Ottawa Hospital Research Institute
• Study Sponsor: Ottawa Hospital Research Institute
• Collaborators: Pfizer

Investigators

• Principal Investigator: Donald W Cameron, MD; The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa

• PRS Account: Ottawa Hospital Research Institute
• Verification Date: February 2020