Healthy
Conditions
Keywords
maraviroc, raltegravir, drug interaction study, healthy volunteers
Brief summary
An open label study to evaluate an interaction between maraviroc and raltegravir in healthy subjects.
Detailed description
Drug interaction study
Interventions
DRUGMaraviroc
300 milligrams(mg) every 12 hours Days 6-11
DRUGRaltegravir
Days 12-14: Raltegravir 400 milligrams(mg) every 12 hours, maraviroc 300 milligrams(mg) every 12 hours (AM doses only on Day 14)
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects between 18 and 55 years of age.
Exclusion criteria
* Evidence or history of clinically significant disease or clinical findings at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | Days 11 and 14 | Effect of raltegravir on pharmacokinetics of maraviroc (comparison of AUCτ of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir). |
| Maraviroc Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) | Days 11 and 14 | Effect of raltegravir on pharmacokinetics of maraviroc (comparison of Cmax of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir). Cmax is the maximum plasma concentration. |
| Raltegravir Pharmacokinetics (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | Days 3 and 14 | Effect of maraviroc on pharmacokinetics of raltegravir (comparison of AUCτ of raltegravir co-administered with maraviroc (Test) versus raltegravir administered alone (Reference)). Pharmacokinetics were assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir). |
| Raltegravir Pharmacokinetics (PK) Parameter: Maximum Concentration (Cmax) | Days 3 and 14 | Effect of maraviroc on pharmacokinetics of raltegravir (comparison of Cmax of raltegravir co-administered with maraviroc (Test) versus raltegravir administered alone (Reference)). Pharmacokinetics assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir). Cmax is the maximum plasma concentration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maraviroc Pharmacokinetic (PK) Parameter: 12-Hour Trough Concentration (C12) | Days 11 and 14 | Effect of raltegravir on pharmacokinetics of maraviroc (comparison of C12 of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir). C12 is the 12-hour trough concentration. |
| Raltegravir Pharmacokinetics (PK) Parameter: 12-Hour Trough Concentration (C12) | Days 3 and 14 | Effect of maraviroc on pharmacokinetics of raltegravir (comparison of C12 of raltegravir co-administered with maraviroc (Test) vs. raltegravir administered alone (Reference)). Pharmacokinetics were assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir). C12 is the 12-hour trough concentration. |
Countries
United States
Participant flow
Recruitment details
One site in the United States
Pre-assignment details
Subjects were to be healthy male or female subjects between the ages of 18 and 55 years, inclusive. Subjects were required to meet all eligibility criteria prior to randomization into the study.
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc / Raltegravir (Alone and Co-administered) All subjects received the following fixed sequence study treatments:
Days 1-3: raltegravir 400 mg every 12 hours (AM dose on Day 3) Days 4-5: washout Days 6-11: maraviroc 300 mg every 12 hours Days 12-14: raltegravir 400 mg every 12 hours and maraviroc 300 mg every 12 hours (AM doses on Day 14). | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Maraviroc / Raltegravir (Alone and Co-administered) |
|---|---|
| Age Continuous | 36.3 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / — | 4 / — | 3 / — |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ)
Effect of raltegravir on pharmacokinetics of maraviroc (comparison of AUCτ of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir).
Time frame: Days 11 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | 2551.9 ng.hr/mL | Standard Deviation 786.68 |
| Maraviroc (Reference) | Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | 2971.6 ng.hr/mL | Standard Deviation 841.65 |
Comparison: The alternate hypothesis of bioequivalence is that there is no difference between treatment groups. For maraviroc, a sample size of 18 subjects provided 99% power that the 90% confidence interval (CI) for the ratio of Test (raltegravir co-administered with maraviroc) to Reference (maraviroc administered alone) treatment for the area under the plasma concentration-time profile over the dosing interval (AUCτ) would lie within the acceptance region of (80%, 125%).90% CI: [79.89, 92.07]Mixed Models Analysis
Primary
Maraviroc Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)
Effect of raltegravir on pharmacokinetics of maraviroc (comparison of Cmax of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir). Cmax is the maximum plasma concentration.
Time frame: Days 11 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Maraviroc Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) | 691.6 ng/mL | Standard Deviation 322.24 |
| Maraviroc (Reference) | Maraviroc Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) | 851.4 ng/mL | Standard Deviation 349.38 |
Comparison: The alternate hypothesis of bioequivalence is that there is no difference between treatment groups. For maraviroc, a sample size of 18 subjects provided 91% power that the 90% CI for the ratio of Test (raltegravir co-administered with maraviroc) to Reference (maraviroc administered alone) treatment for the maximum concentration (Cmax) would lie within the acceptance region of (80%, 125%).90% CI: [67.19, 94.02]Mixed Models Analysis
Primary
Raltegravir Pharmacokinetics (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ)
Effect of maraviroc on pharmacokinetics of raltegravir (comparison of AUCτ of raltegravir co-administered with maraviroc (Test) versus raltegravir administered alone (Reference)). Pharmacokinetics were assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir).
Time frame: Days 3 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Raltegravir Pharmacokinetics (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | 6287.5 ng.hr/mL | Standard Deviation 3979.3 |
| Maraviroc (Reference) | Raltegravir Pharmacokinetics (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ) | 9122.4 ng.hr/mL | Standard Deviation 5311.34 |
Comparison: For raltegravir, a sample size of 18 subjects provided 90% CIs for the difference between treatments of raltegravir (±0.205) on the natural log scale for AUCτ, with 90% coverage probability.90% CI: [44.27, 90.39]Mixed Models Analysis
Primary
Raltegravir Pharmacokinetics (PK) Parameter: Maximum Concentration (Cmax)
Effect of maraviroc on pharmacokinetics of raltegravir (comparison of Cmax of raltegravir co-administered with maraviroc (Test) versus raltegravir administered alone (Reference)). Pharmacokinetics assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir). Cmax is the maximum plasma concentration.
Time frame: Days 3 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Raltegravir Pharmacokinetics (PK) Parameter: Maximum Concentration (Cmax) | 2169.6 ng/mL | Standard Deviation 1570.58 |
| Maraviroc (Reference) | Raltegravir Pharmacokinetics (PK) Parameter: Maximum Concentration (Cmax) | 3026.6 ng/mL | Standard Deviation 2030.15 |
Comparison: For raltegravir, a sample size of 18 subjects provided 90% CIs for the difference between treatments of raltegravir (±0.293) on the natural log scale for Cmax, with 90% coverage probability.90% CI: [41.22, 108.15]Mixed Models Analysis
Other Pre-specified
Maraviroc Pharmacokinetic (PK) Parameter: 12-Hour Trough Concentration (C12)
Effect of raltegravir on pharmacokinetics of maraviroc (comparison of C12 of raltegravir co-administered with maraviroc (Test) versus maraviroc administered alone (Reference)). Pharmacokinetics were assessed on Day 11 (maraviroc) and Day 14 (maraviroc and raltegravir). C12 is the 12-hour trough concentration.
Time frame: Days 11 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Maraviroc Pharmacokinetic (PK) Parameter: 12-Hour Trough Concentration (C12) | 48.34 ng/mL | Standard Deviation 13.7 |
| Maraviroc (Reference) | Maraviroc Pharmacokinetic (PK) Parameter: 12-Hour Trough Concentration (C12) | 53.36 ng/mL | Standard Deviation 14.03 |
Comparison: The alternate hypothesis of bioequivalence is that there is no difference between treatment groups.90% CI: [85.28, 95.68]Mixed Models Analysis
Other Pre-specified
Raltegravir Pharmacokinetics (PK) Parameter: 12-Hour Trough Concentration (C12)
Effect of maraviroc on pharmacokinetics of raltegravir (comparison of C12 of raltegravir co-administered with maraviroc (Test) vs. raltegravir administered alone (Reference)). Pharmacokinetics were assessed on Day 3 (raltegravir) and Day 14 (maraviroc and raltegravir). C12 is the 12-hour trough concentration.
Time frame: Days 3 and 14
Population: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc + Raltegravir (Test) | Raltegravir Pharmacokinetics (PK) Parameter: 12-Hour Trough Concentration (C12) | 51.16 ng/mL | Standard Deviation 22.64 |
| Maraviroc (Reference) | Raltegravir Pharmacokinetics (PK) Parameter: 12-Hour Trough Concentration (C12) | 73.69 ng/mL | Standard Deviation 36.21 |
90% CI: [57.82, 90.71]Mixed Models Analysis