HIV-1 Infection, HIV Infection, Mycobacterium Avium Complex (MAC)
Conditions
Keywords
healthy volunteers
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.
Interventions
DRUGRifabutin
Substance: Rifabutin Daily dose: oral, 300 mg once daily (8:00 am) for 10 days
DRUGMaraviroc
Substance maraviroc daily dose 300 mg twice daily (8:00 am and 8:00 pm) for 15 days
Sponsors
Pfizer
Ottawa Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Safety/Tolerability of the Treatments | 30 days | description and frequency of adverse events for all participants during the study. |
Countries
Canada
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.
Participants by arm
| Arm | Count |
|---|---|
| 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
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 | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Maraviroc | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 14 Participants | — |
| Age, Continuous | 33 years STANDARD_DEVIATION 13 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Canada | 14 participants | — |
| Sex: Female, Male Female | 7 Participants | — |
| Sex: Female, Male Male | 7 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 11 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
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).
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..
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Maraviroc only Cmax (μg/L) | 304.6 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Maraviroc only C12 (μg/L) | 23.3 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Maraviroc + Rifabutin Cmax (μg/L) | 239.8 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Maraviroc + Rifabutin C12 (μg/L) | 16.3 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Rifabutin Cmax (μg/L) | 542.2 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | Rifabutin C24 (μg/L) | 71.2 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | 25-O-desacetyl rifabutin Cmax (μg/L) | 42.3 μg/L |
| Maraviroc | Maraviroc and Rifabutin C12/C24/Cmax PK Concentrations in Plasma. | 25-O-desacetyl rifabutin C24 (μg/L) | 5.5 μg/L |
Primary
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).
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..
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Maraviroc | Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 | Maraviroc only AUC (h*μg/L) | 1026.2 h*μg/L |
| Maraviroc | Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 | Maraviroc + Rifabutin AUC (h*μg/L) | 847.0 h*μg/L |
| Maraviroc | Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 | Rifabutin AUC (h*μg/L) | 4221.9 h*μg/L |
| Maraviroc | Pharmacokinetics of Maraviroc and Rifabutin AUC 0-12/24 | 25-O-desacetyl rifabutin AUC (h*μg/L) | 331.9 h*μg/L |
Secondary
Safety/Tolerability of the Treatments
description and frequency of adverse events for all participants during the study.
Time frame: 30 days
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Maraviroc | Safety/Tolerability of the Treatments | Maraviroc | Number of Participants with Adverse Events | 6 Participants |
| Maraviroc | Safety/Tolerability of the Treatments | Maraviroc | Number of Participants without Adverse Events | 8 Participants |
| Maraviroc | Safety/Tolerability of the Treatments | Maraviroc + Rifabutin | Number of Participants with Adverse Events | 7 Participants |
| Maraviroc | Safety/Tolerability of the Treatments | Maraviroc + Rifabutin | Number of Participants without Adverse Events | 7 Participants |