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

NCT01894776 | Completed Phase 1 Results DMC

• 1 other identifier: 2013 0080-01H
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

healthy volunteers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Safety/Tolerability of the Treatments

  30 days

Study Arms (1)

Maraviroc

EXPERIMENTAL

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; Drug: Maraviroc

Interventions

Rifabutin DRUG

Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days

Also known as: Mycobutin, RFB

Maraviroc

Maraviroc DRUG

Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days

Also known as: Celsentri, MVC

Maraviroc

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Pfizer: collaborator

Study Sites (1)

The Ottawa Hospital -General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (1)

• 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.

  PMID: 31647836 RESULT

MeSH Terms

Conditions

HIV Infections; Mycobacterium avium-intracellulare Infection

Interventions

Rifabutin; Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Bill Cameron
• Organization: Ottawa Hospital Research Institute

bcameron@toh.ca

613-737-8899

Study Officials

• Donald W Cameron, MD

  The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: July 10, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2015
• Last Updated: March 10, 2020
• Results First Posted: March 10, 2020

Record last verified: 2020-02

Locations

CA (1)