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

• Sponsor: Ottawa Hospital Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01894776
• Collaborator: Pfizer (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection; HIV-1 Infection; Mycobacterium Avium Complex (MAC)	Drug: Rifabutin; Drug: Maraviroc	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Drug Interaction Study Investigating the Effect of Rifabutin on the Pharmacokinetics of Maraviroc
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 [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).

2. Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. [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).

Secondary Outcome Measures

1. Safety/Tolerability of the Treatments [30 days]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ottawa Hospital -General Campus	Ottawa	Ontario	Canada	K1H 8L6

Sponsors and Collaborators

• Ottawa Hospital Research Institute
• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ottawa Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT01894776
• Other Study ID Numbers: 2013 0080-01H
• First Posted: Jul 10, 2013
• Last Update Posted: Mar 10, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Ottawa Hospital Research Institute: healthy volunteers
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycobacterium avium-intracellulare Infection; Maraviroc; Rifabutin

Study Results

Participant Flow

Recruitment Details	The Clinical Investigation Unit (CIU) at the OHRI has a database of healthy volunteers interested in participating in clinical studies who were contacted and recruited by phone or email. The first patient was recruited on 06 Sept 2013 and the last follow-up visit was on 23 Dec 2013.

Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Period Title: Overall Study
STARTED	15
COMPLETED	14
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33 (13)
Sex: Female, Male (Count of Participants)
Female	7 50%
Male	7 50%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Canada	14 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24
Description	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).
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..

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Measure Participants	14
Maraviroc only AUC (h*μg/L)	1026.2
Maraviroc + Rifabutin AUC (h*μg/L)	847.0
Rifabutin AUC (h*μg/L)	4221.9
25-O-desacetyl rifabutin AUC (h*μg/L)	331.9

2. Primary Outcome

Title	Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma.
Description	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).
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..

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Measure Participants	14
Maraviroc only Cmax (μg/L)	304.6
Maraviroc only C12 (μg/L)	23.3
Maraviroc + Rifabutin Cmax (μg/L)	239.8
Maraviroc + Rifabutin C12 (μg/L)	16.3
Rifabutin Cmax (μg/L)	542.2
Rifabutin C24 (μg/L)	71.2
25-O-desacetyl rifabutin Cmax (μg/L)	42.3
25-O-desacetyl rifabutin C24 (μg/L)	5.5

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Measure Participants	14
Number of Participants with Adverse Events	6 42.9%
Number of Participants without Adverse Events	8 57.1%
Number of Participants with Adverse Events	7 50%
Number of Participants without Adverse Events	7 50%

Adverse Events

Time Frame	30 days.
Arm/Group Title	Maraviroc
Arm/Group Description	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 Rifabutin: Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days Maraviroc: Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
All Cause Mortality
	Maraviroc
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Maraviroc
	Affected / at Risk (%)	# Events
Total	11/14 (78.6%)
General disorders
Fever	2/14 (14.3%)
Musculoskeletal and connective tissue disorders
Joint pain	2/14 (14.3%)
Muscle pain	1/14 (7.1%)
Nervous system disorders
Headache	6/14 (42.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.