Human Immunodeficiency Virus (HIV) Infection
Conditions
Keywords
maraviroc, pharmacokinetics, renal impairment
Brief summary
The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.
Interventions
DRUGMaraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
DRUGRitonavir
Ritonavir 100 mg capsule twice daily x 7 days
DRUGSaquinavir
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Stable Renal Function defined as ≤20% (25% for normal renal function) difference between 2 measurements of serum creatinine obtained on 2 occasions separated by at least 2 weeks. * Body Mass Index (BMI) of approximately 18 to 40 kg/m2 inclusive. * Total body weight \>50 kg (110 lbs). * Male or female subjects between the ages of 18 and 85 years.
Exclusion criteria
* Subjects with acute renal disease and/or history of renal transplant. * Supine BP at Screening ≥160 mm Hg systolic or ≥95 mm Hg diastolic. * Supine BP at Screening ≤80 mm Hg systolic or ≤40 mm Hg diastolic.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) measured in nanograms \* hour divided by milliliters (ng\*hr/mL). |
| AUCtau | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | AUCtau: area under the plasma concentration-time profile from time zero to the end of the dosing interval (tau); measured in nanograms \* hours divided by milliliters (ng.hr/mL). |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Half-life (t1/2) | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Elimination half-life (t1/2) measured in hours: time required for half the quantity of maraviroc to be metabolized or eliminated by normal biological processes. |
| Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Renal clearance (CLR) measured in milliliters per minute (mL/min). |
| Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg). |
| Plasma Protein Binding | 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 | Percent protein binding (protein unbound maraviroc (MVC) fraction \[percent free\]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound. |
| Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up | Number of subjects with absolute values of supine systolic blood pressure (BP) measured in millimeters of mercury (mm/Hg), range: \<90 mmHg; and supine diastolic blood pressure, range: \<50 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine systolic BP ≥ 30 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine diastolic BP ≥ 20 mmHg. |
| Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up | Number of subjects with pulse rate \< 40 beats per minute (BPM), number of subjects with pulse rate \> 120 BPM. |
| Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Normal renal function: screening, Day -3 and Day -1; normal renal function, mild and moderate RI: Day 7 to Day 9 and follow-up; severe RI: screening, Day 1, Day 3, Day 4, and follow-up; ESRD: screening, Day 1, Day 3, Day 4, and follow-up | Single 12-lead ECG: number of subjects with maximum QTC interval, maximum QTCB interval (Bazett's correction), and maximum QTCF interval (Friderica's correction) measured in milliseconds (msec); range: 450 to \<480 msec, 480 to \<500 msec, and \>500 msec. Maximum QTC interval increase from Baseline; citeria: change = ≥ 30 msec to \< 60 msec, and change = ≥ 60 msec. |
| Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD | Before dialysis | CLdD: dialysate clearance before dialysis; measured in milliliters per minute. |
| Area Under the Time Curve From 0 to Infinity (AUCinf) | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 | Area under the plasma concentration-time profile from time zero to the time infinate in subjects who received single dose treatment; measured in nanograms \* hour divided by millilters (ng\*hr/mL). |
| Time of First Occurrence (Tmax) | Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. | Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured. |
Countries
Germany
Participant flow
Recruitment details
Two centers took part in this study between 15 July 2008 and 21 November 2008.
Pre-assignment details
Subjects were enrolled into treatment groups (healthy subjects, mild, moderate, severe renal impairment, or end stage renal impairment on hemodialysis) based on creatinine clearance results obtained closest to the dosing date at screening as determined by the Cockcroft-Gault equation (with the exception of subjects undergoing hemodialysis).
Participants by arm
| Arm | Count |
|---|---|
| Healthy Subjects Subjects with Normal Renal Function (Creatinine Clearance \> 80mL/min) | 6 |
| Mild Renal Impairment Subjects with Mild Renal Impairment (Creatinine Clearance \>50 and ≤80 mL/min) | 6 |
| Moderate Renal Impairment Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min) | 6 |
| Severe Renal Impairment Subjects with Severe Renal Impairment (Creatinine Clearance \<30 mL/min) | 6 |
| ESRD on Hemodialysis Subjects with End Stage Renal Disease Requiring Regular Hemodialysis 3 Times a Week for at Least 6 Weeks Prior to Screening (Creatinine Clearance \<30 mL/min) | 6 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part 1a: Normal/Mild/Moderate Group | Adverse Event | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Healthy Subjects | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | ESRD on Hemodialysis | Total |
|---|---|---|---|---|---|---|
| Age, Customized 18 - 44 years | 0 years | 0 years | 1 years | 1 years | 1 years | 3 years |
| Age, Customized 45 - 64 years | 5 years | 4 years | 0 years | 2 years | 4 years | 15 years |
| Age, Customized >= 65 years | 1 years | 2 years | 5 years | 3 years | 1 years | 12 years |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 6 / 6 | 6 / 6 | 1 / 6 | 3 / 6 | 2 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) measured in nanograms \* hour divided by milliliters (ng\*hr/mL).
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 7356.3 ng*hr/mL | Standard Deviation 2313.45 |
| Mild Renal Impairment: Multiple Dose | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 9502.1 ng*hr/mL | Standard Deviation 3599.32 |
| Moderate Renal Impairment: Multiple Dose | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 6496.0 ng*hr/mL | Standard Deviation 1795.89 |
| Healthy Subjects: Single Dose | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 1320.7 ng*hr/mL | Standard Deviation 988.66 |
| Severe Renal Impairment: Single Dose | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 4255.5 ng*hr/mL | Standard Deviation 2424.19 |
| ESRD: Single Dose; After Dialysis | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 2636.5 ng*hr/mL | Standard Deviation 1123.34 |
| ESRD: Single Dose; Before Dialysis | Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) | 2770.1 ng*hr/mL | Standard Deviation 1356.56 |
Comparison: Ratio (%) test (mild) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.90% CI: [92.16, 181.04]ANOVA
Comparison: Ratio (%) test (moderate) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.90% CI: [61.97, 125.83]ANOVA
Comparison: Ratio (%) test (severe) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.90% CI: [171.97, 603.78]ANOVA
Primary
AUCtau
AUCtau: area under the plasma concentration-time profile from time zero to the end of the dosing interval (tau); measured in nanograms \* hours divided by milliliters (ng.hr/mL).
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest. AUCtau for end stage renal disease subjects was not determined.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | AUCtau | 5341.4 ng*hr/mL | Standard Deviation 1498.27 |
| Mild Renal Impairment: Multiple Dose | AUCtau | 8118.7 ng*hr/mL | Standard Deviation 2995.27 |
| Moderate Renal Impairment: Multiple Dose | AUCtau | 6193.3 ng*hr/mL | Standard Deviation 1762.41 |
Comparison: Ratio (%) test (mild) / reference (normal).90% CI: [109.53, 210.92]ANOVA
Comparison: Ratio (%) test (moderate) / reference (normal).90% CI: [82.23, 163.5]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Maximum Observed Plasma Concentration (Cmax) | 950.91 ng/mL | Standard Deviation 220.368 |
| Mild Renal Impairment: Multiple Dose | Maximum Observed Plasma Concentration (Cmax) | 1150.74 ng/mL | Standard Deviation 392.167 |
| Moderate Renal Impairment: Multiple Dose | Maximum Observed Plasma Concentration (Cmax) | 674.20 ng/mL | Standard Deviation 275.722 |
| Healthy Subjects: Single Dose | Maximum Observed Plasma Concentration (Cmax) | 335.60 ng/mL | Standard Deviation 393.024 |
| Severe Renal Impairment: Single Dose | Maximum Observed Plasma Concentration (Cmax) | 801.16 ng/mL | Standard Deviation 525.656 |
| ESRD: Single Dose; After Dialysis | Maximum Observed Plasma Concentration (Cmax) | 576.7 ng/mL | Standard Deviation 339.27 |
| ESRD: Single Dose; Before Dialysis | Maximum Observed Plasma Concentration (Cmax) | 478.5 ng/mL | Standard Deviation 198.81 |
Comparison: Ratio (%) test (mild) / reference (normal).90% CI: [83.15, 176.13]ANOVA
Comparison: Ratio (%) test (moderate) / reference (normal).90% CI: [47.83, 105.1]ANOVA
Comparison: Ratio (%) test (severe) / reference (normal).90% CI: [106.83, 533.48]ANOVA
Secondary
Area Under the Time Curve From 0 to Infinity (AUCinf)
Area under the plasma concentration-time profile from time zero to the time infinate in subjects who received single dose treatment; measured in nanograms \* hour divided by millilters (ng\*hr/mL).
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest. AUC infinity was not determined for subjects in the multiple dose treatment groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Area Under the Time Curve From 0 to Infinity (AUCinf) | 1348.4 ng*hr/mL | Standard Deviation 986.65 |
| Mild Renal Impairment: Multiple Dose | Area Under the Time Curve From 0 to Infinity (AUCinf) | 4367.7 ng*hr/mL | Standard Deviation 2518.78 |
| Moderate Renal Impairment: Multiple Dose | Area Under the Time Curve From 0 to Infinity (AUCinf) | 2677.4 ng*hr/mL | Standard Deviation 1149.85 |
| Healthy Subjects: Single Dose | Area Under the Time Curve From 0 to Infinity (AUCinf) | 2805.5 ng*hr/mL | Standard Deviation 1374.71 |
Comparison: Ratio (%) test (severe) / reference (normal).90% CI: [174.32, 601.88]ANOVA
Secondary
Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae
Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).
Time frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | 41.6 mg | Standard Deviation 22.45 |
| Mild Renal Impairment: Multiple Dose | Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | 39.1 mg | Standard Deviation 11.23 |
| Moderate Renal Impairment: Multiple Dose | Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | 24.9 mg | Standard Deviation 8.88 |
| Healthy Subjects: Single Dose | Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | 10.8 mg | Standard Deviation 7.41 |
| Severe Renal Impairment: Single Dose | Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae | 8.4 mg | Standard Deviation 6.35 |
Secondary
Half-life (t1/2)
Elimination half-life (t1/2) measured in hours: time required for half the quantity of maraviroc to be metabolized or eliminated by normal biological processes.
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Half-life (t1/2) | 14.22 hour | Standard Deviation 1.166 |
| Mild Renal Impairment: Multiple Dose | Half-life (t1/2) | 16.84 hour | Standard Deviation 5.568 |
| Moderate Renal Impairment: Multiple Dose | Half-life (t1/2) | 16.99 hour | Standard Deviation 3.141 |
| Healthy Subjects: Single Dose | Half-life (t1/2) | 14.36 hour | Standard Deviation 4.03 |
| Severe Renal Impairment: Single Dose | Half-life (t1/2) | 17.29 hour | Standard Deviation 4.171 |
| ESRD: Single Dose; After Dialysis | Half-life (t1/2) | 15.03 hour | Standard Deviation 3.329 |
| ESRD: Single Dose; Before Dialysis | Half-life (t1/2) | 13.86 hour | Standard Deviation 1.051 |
Secondary
Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD
CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
Time frame: Before dialysis
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD | 36.42 mL/min | Standard Deviation 12.71 |
Secondary
Plasma Protein Binding
Percent protein binding (protein unbound maraviroc (MVC) fraction \[percent free\]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.
Time frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Plasma Protein Binding | minimum protein unbound MVC fraction | 19.7 percent free |
| Healthy Subjects: Multiple Dose | Plasma Protein Binding | maximum protein unbound MVC fraction | 26.6 percent free |
| Mild Renal Impairment: Multiple Dose | Plasma Protein Binding | minimum protein unbound MVC fraction | 15.3 percent free |
| Mild Renal Impairment: Multiple Dose | Plasma Protein Binding | maximum protein unbound MVC fraction | 29.1 percent free |
| Moderate Renal Impairment: Multiple Dose | Plasma Protein Binding | minimum protein unbound MVC fraction | 18.1 percent free |
| Moderate Renal Impairment: Multiple Dose | Plasma Protein Binding | maximum protein unbound MVC fraction | 31.6 percent free |
| Healthy Subjects: Single Dose | Plasma Protein Binding | minimum protein unbound MVC fraction | 14.6 percent free |
| Healthy Subjects: Single Dose | Plasma Protein Binding | maximum protein unbound MVC fraction | 28.2 percent free |
| Severe Renal Impairment: Single Dose | Plasma Protein Binding | minimum protein unbound MVC fraction | 19.2 percent free |
| Severe Renal Impairment: Single Dose | Plasma Protein Binding | maximum protein unbound MVC fraction | 28.1 percent free |
| ESRD: Single Dose; After Dialysis | Plasma Protein Binding | minimum protein unbound MVC fraction | 18.2 percent free |
| ESRD: Single Dose; After Dialysis | Plasma Protein Binding | maximum protein unbound MVC fraction | 27.8 percent free |
Secondary
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function
Renal clearance (CLR) measured in milliliters per minute (mL/min).
Time frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | 105.7 mL/min | Standard Deviation 56 |
| Mild Renal Impairment: Multiple Dose | Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | 77.2 mL/min | Standard Deviation 36.71 |
| Moderate Renal Impairment: Multiple Dose | Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | 62.5 mL/min | Standard Deviation 12.57 |
| Healthy Subjects: Single Dose | Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | 110.0 mL/min | Standard Deviation 38.67 |
| Severe Renal Impairment: Single Dose | Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function | 26.6 mL/min | Standard Deviation 18.84 |
Secondary
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals
Single 12-lead ECG: number of subjects with maximum QTC interval, maximum QTCB interval (Bazett's correction), and maximum QTCF interval (Friderica's correction) measured in milliseconds (msec); range: 450 to \<480 msec, 480 to \<500 msec, and \>500 msec. Maximum QTC interval increase from Baseline; citeria: change = ≥ 30 msec to \< 60 msec, and change = ≥ 60 msec.
Time frame: Normal renal function: screening, Day -3 and Day -1; normal renal function, mild and moderate RI: Day 7 to Day 9 and follow-up; severe RI: screening, Day 1, Day 3, Day 4, and follow-up; ESRD: screening, Day 1, Day 3, Day 4, and follow-up
Population: Safety analysis set: all subjects who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 1 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 1 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 1 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 1 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 1 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 1 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 2 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 1 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 1 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | QTC Interval Increase from BL: change ≥ 60 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 450 to < 480 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Max. QTC Interval Increase from BL: change ≥30 <60 | 1 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 450 to < 480 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCB Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: > 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTC Interval: 480 to < 500 msec | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum EGC QTC, QTCB and QTCF Intervals | Maximum QTCF Interval: 450 to 480 msec | 0 subjects |
Secondary
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure
Number of subjects with absolute values of supine systolic blood pressure (BP) measured in millimeters of mercury (mm/Hg), range: \<90 mmHg; and supine diastolic blood pressure, range: \<50 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine systolic BP ≥ 30 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine diastolic BP ≥ 20 mmHg.
Time frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up
Population: Safety analysis set: all subjects who received study medication. BL: Baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 1 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 1 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Decrease from BL: Supine Systolic BP ≥ 30 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Systolic BP≥ 30 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximun Decrease from BL: Supine Diastolic BP ≥20 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Diastolic Blood Pressure (BP) <50 mmHg | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | Maximum Increase from BL: Supine Diastolic BP≥ 20 | 0 subjects |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure | BL Supine Systolic Blood Pressure (BP) <90 mmHg | 0 subjects |
Secondary
Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute
Number of subjects with pulse rate \< 40 beats per minute (BPM), number of subjects with pulse rate \> 120 BPM.
Time frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up
Population: Safety analysis set: all subjects who received study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| Healthy Subjects: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| Mild Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| Moderate Renal Impairment: Multiple Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| Healthy Subjects: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| Severe Renal Impairment: Single Dose | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| ESRD: Single Dose; After Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate <40 BPM | 0 bpm |
| ESRD: Single Dose; Before Dialysis | Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Pulse Rate < 40 and > 120 Beats Per Minute | Supine Pulse Rate >120 BPM | 0 bpm |
Secondary
Time of First Occurrence (Tmax)
Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Population: Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Subjects: Multiple Dose | Time of First Occurrence (Tmax) | 1.000 hours |
| Mild Renal Impairment: Multiple Dose | Time of First Occurrence (Tmax) | 1.500 hours |
| Moderate Renal Impairment: Multiple Dose | Time of First Occurrence (Tmax) | 2.000 hours |
| Healthy Subjects: Single Dose | Time of First Occurrence (Tmax) | 2.500 hours |
| Severe Renal Impairment: Single Dose | Time of First Occurrence (Tmax) | 2.500 hours |
| ESRD: Single Dose; After Dialysis | Time of First Occurrence (Tmax) | 3.000 hours |
| ESRD: Single Dose; Before Dialysis | Time of First Occurrence (Tmax) | 2.000 hours |