AIDS
Conditions
Keywords
pharmacodynamics. maraviroc, vardenafil, blood pressure
Brief summary
The objective of this study was to estimate the effects of a single dose of vardenafil on the blood pressure (BP) in subjects receiving maraviroc (MVC) (dosed to steady-state) and to assess the safety and tolerability of MVC in subjects receiving a single dose of vardenafil.
Interventions
DRUGMaraviroc
Maraviroc 300 mg twice daily for 3 - 4 days plus a single oral dose of Vardenafil 20 mg.
DRUGVardenafil
Maraviroc 300 mg twice daily for 3 - 4 days plus a single oral dose of Vardenafil 20 mg.
DRUGPlacebo
Maraviroc 300 mg twice daily for 3 - 4 days plus a single oral dose of Placebo.
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects. no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead electrocardiogram and clinical laboratory tests. * Body mass index (BMI) of approximately 18 to 30 kg/m2; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. * Subjects with a supine systolic BP of greater than 140 mm Hg, or a supine diastolic BP of greater than 90 mm Hg, either at Screening or at the predose measurements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standing and Supine Systolic and Diastolic Blood Pressure (BP) | 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post Vardenafil or Placebo dose | Supine BP was taken after subjects rested for 5 minutes supine. Subjects then sat for 2 minutes and stood for 2 minutes then standing BP taken. Duplicate supine and standing BP measurements were taken per the protocol. The average of the duplicate measurements was calculated prior to data analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standing and Supine Pulse Rate | 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post Vardenafil or Placebo dose | Supine pulse rate measurement was taken after subject rested for 5 minutes supine. Subject sat for 2 minutes, then stood for 2 minutes and standing measurement taken. Duplicate supine and standing pulse rate measurements taken per protocol. Average of duplicate measurements calculated prior to data analysis. |
| Postural Changes in Systolic and Diastolic Blood Pressure | Baseline, 6 and 12 hours post dose on Day 1 from the First Day of each Treatment Leg | Postural change calculated as position 1 (standing) value minus the position 2 (supine) value. Baseline was the average of 3 predose measurements at each period. Means of replicates were used in calculations. |
| Postural Changes in Pulse Rate | Baseline, 6 and 12 hours post dose on Day 1 from the First Day of each Treatment Leg | Postural change calculated as position 1 (standing) value minus position 2 (supine) value. Baseline was the average of the 3 predose measurements at each period. Means of Replicates were used in calculations. |
| Number of Subjects With Postural Hypotension | Period 1 and Period 2 (up to 8 days) | Postural (orthostatic) hypotension defined as 1) decrease in standing-supine diastolic blood pressure (BP) greater than or equal to 10 mm Hg; 2) decrease in standing-supine systolic BP greater than or equal to 20 mm Hg; or 3) standing systolic BP less than 90 mm Hg. Assessed at Period 1 and Period 2 BP measurement timepoints post maraviroc dose. |
Countries
Belgium
Participant flow
Pre-assignment details
All subjects received 3 to 4 days of maraviroc 300 mg twice daily (BID) before receiving single oral doses of either vardenafil 20 mg (Treatment A) or placebo (Treatment B).
Participants by arm
| Arm | Count |
|---|---|
| All Subjects In this 2-way crossover study, in Period 1, all 18 subjects were randomized to receive a single dose of either vardenafil 20 mg (Treatment A) or placebo (Treatment B), subsequent to treatment with 3 to 4 days of maraviroc 300 mg BID. All subjects were then crossed over to receive the second treatment in Period 2. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age Continuous | 34.6 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 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 / — | 16 / — | 5 / — |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Standing and Supine Systolic and Diastolic Blood Pressure (BP)
Supine BP was taken after subjects rested for 5 minutes supine. Subjects then sat for 2 minutes and stood for 2 minutes then standing BP taken. Duplicate supine and standing BP measurements were taken per the protocol. The average of the duplicate measurements was calculated prior to data analysis.
Time frame: 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post Vardenafil or Placebo dose
Population: The vital sign analysis population was defined as all enrolled subjects who received at least 1 dose of study medication and had at least 1 vital sign parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 12 hour post Maraviroc dose | 128.38 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 1.5 hour post Maraviroc dose | 68.06 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 2 hour post Maraviroc dose | 113.45 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 2 hour post Maraviroc dose | 66.31 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 2.5 hour post Maraviroc dose | 114.67 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 2.5 hour post Maraviroc dose | 66.98 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 3 hour post Maraviroc dose | 114.11 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 3 hour post Maraviroc dose | 67.28 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 4 hour post Maraviroc dose | 115.89 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 4 hour post Maraviroc dose | 68.37 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 6 hour post Maraviroc dose | 116.45 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 6 hour post Maraviroc dose | 65.67 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 8 hour post Maraviroc dose | 116.61 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 8 hour post Maraviroc dose | 66.34 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 12 hour post Maraviroc dose | 122.81 mm Hg | Standard Error 1.1523 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 12 hour post Maraviroc dose | 67.95 mm Hg | Standard Error 0.7184 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 1.5 hour post Maraviroc dose | 120.82 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 2 hour post Maraviroc dose | 118.49 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 2 hour post Maraviroc dose | 74.90 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 2.5 hour post Maraviroc dose | 115.52 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP 2.5 hour post Maraviroc dose | 72.29 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 3 hour post Maraviroc dose | 117.10 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 3 hour post Maraviroc dose | 73.73 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 4 hour post Maraviroc dose | 119.35 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 4 hour post Maraviroc dose | 77.29 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 6 hour post Maraviroc dose | 118.29 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 6 hour post Maraviroc dose | 73.34 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 8 hour post Maraviroc dose | 120.43 mm Hg | Standard Error 1.6525 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 8 hour post Maraviroc dose | 74.06 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 12 hour post Maraviroc dose | 78.65 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP 1.5 hour post Maraviroc dose | 74.81 mm Hg | Standard Error 1.0102 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 1.5 hour post Maraviroc dose | 118.36 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 8 hour post Maraviroc dose | 77.32 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 1.5 hour post Maraviroc dose | 119.47 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP 1.5 hour post Maraviroc dose | 78.74 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 1.5 hour post Maraviroc dose | 69.99 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 4 hour post Maraviroc dose | 78.38 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 2 hour post Maraviroc dose | 118.44 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 2 hour post Maraviroc dose | 125.40 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 2 hour post Maraviroc dose | 69.27 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 12 hour post Maraviroc dose | 128.65 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 2.5 hour post Maraviroc dose | 119.55 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 2 hour post Maraviroc dose | 80.69 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 2.5 hour post Maraviroc dose | 70.80 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 6 hour post Maraviroc dose | 120.59 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 3 hour post Maraviroc dose | 116.16 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 2.5 hour post Maraviroc dose | 121.32 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 3 hour post Maraviroc dose | 69.05 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 8 hour post Maraviroc dose | 123.90 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 4 hour post Maraviroc dose | 117.97 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP 2.5 hour post Maraviroc dose | 78.94 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 4 hour post Maraviroc dose | 69.24 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 6 hour post Maraviroc dose | 76.77 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 6 hour post Maraviroc dose | 118.75 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 3 hour post Maraviroc dose | 121.37 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 6 hour post Maraviroc dose | 66.52 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 12 hour post Maraviroc dose | 80.91 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 8 hour post Maraviroc dose | 120.83 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Diastolic BP: 3 hour post Maraviroc dose | 77.38 mm Hg | Standard Error 1.0102 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 8 hour post Maraviroc dose | 68.85 mm Hg | Standard Error 0.7184 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 1.5 hour post Maraviroc dose | 125.18 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Systolic BP: 12 hour post Maraviroc dose | 124.75 mm Hg | Standard Error 1.1523 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Standing Systolic BP: 4 hour post Maraviroc dose | 121.40 mm Hg | Standard Error 1.6525 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Systolic and Diastolic Blood Pressure (BP) | Supine Diastolic BP: 12 hour post Maraviroc dose | 70.27 mm Hg | Standard Error 0.7184 |
Comparison: 1.5 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-3.8, 1.59]Mixed Models Analysis
Comparison: 1.5 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-3.55, -0.31]Mixed Models Analysis
Comparison: 2 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-7.69, -2.3]Mixed Models Analysis
Comparison: 2 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.58, -1.34]Mixed Models Analysis
Comparison: 2.5 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-7.58, -2.19]Mixed Models Analysis
Comparison: 2.5 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-5.44, -2.2]Mixed Models Analysis
Comparison: 3 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.74, 0.64]Mixed Models Analysis
Comparison: 3 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-3.38, -0.15]Mixed Models Analysis
Comparison: 4 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.77, 0.62]Mixed Models Analysis
Comparison: 4 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-2.49, 0.74]Mixed Models Analysis
Comparison: 6 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.99, 0.39]Mixed Models Analysis
Comparison: 6 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-2.47, 0.77]Mixed Models Analysis
Comparison: 8 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-6.91, -1.52]Mixed Models Analysis
Comparison: 8 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.13, -0.9]Mixed Models Analysis
Comparison: 12 hour post-dose for supine systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.63, 0.76]Mixed Models Analysis
Comparison: 12 hour post-dose for supine diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-3.94, -0.7]Mixed Models Analysis
Comparison: 1.5 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-8.22, -0.5]Mixed Models Analysis
Comparison: 1.5 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-6.29, -1.56]Mixed Models Analysis
Comparison: 2 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-10.77, -3.05]Mixed Models Analysis
Comparison: 2 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-8.15, -3.42]Mixed Models Analysis
Comparison: 2.5 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-9.66, -1.94]Mixed Models Analysis
Comparison: 2.5 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-9.01, -4.29]Mixed Models Analysis
Comparison: 3 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-8.13, -0.41]Mixed Models Analysis
Comparison: 3 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-6.01, -1.29]Mixed Models Analysis
Comparison: 4 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-5.91, 1.81]Mixed Models Analysis
Comparison: 4 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-3.46, 1.27]Mixed Models Analysis
Comparison: 6 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-6.16, 1.56]Mixed Models Analysis
Comparison: 6 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-5.79, -1.06]Mixed Models Analysis
Comparison: 8 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-7.33, 0.39]Mixed Models Analysis
Comparison: 8 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-5.62, -0.9]Mixed Models Analysis
Comparison: 12 hour post-dose for standing systolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.13, 3.59]Mixed Models Analysis
Comparison: 12 hour post-dose for standing diastolic BP~Vardenafil minus Placebo~A total sample size of 18 subjects provides 90% confidence intervals for the difference between vardenafil and placebo of ±5.90 on the standing diastolic BP with 98% coverage probability at each time postdose.90% CI: [-4.62, 0.1]Mixed Models Analysis
Secondary
Number of Subjects With Postural Hypotension
Postural (orthostatic) hypotension defined as 1) decrease in standing-supine diastolic blood pressure (BP) greater than or equal to 10 mm Hg; 2) decrease in standing-supine systolic BP greater than or equal to 20 mm Hg; or 3) standing systolic BP less than 90 mm Hg. Assessed at Period 1 and Period 2 BP measurement timepoints post maraviroc dose.
Time frame: Period 1 and Period 2 (up to 8 days)
Population: The vital sign analysis population was defined as all enrolled subjects who received at least 1 dose of study medication and had at least 1 vital sign parameter in at least 1 treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc + Vardenafil (Treatment A) | Number of Subjects With Postural Hypotension | 0 participants |
| Maraviroc + Placebo (Treatment B) | Number of Subjects With Postural Hypotension | 0 participants |
Secondary
Postural Changes in Pulse Rate
Postural change calculated as position 1 (standing) value minus position 2 (supine) value. Baseline was the average of the 3 predose measurements at each period. Means of Replicates were used in calculations.
Time frame: Baseline, 6 and 12 hours post dose on Day 1 from the First Day of each Treatment Leg
Population: The vital sign analysis population was defined as all enrolled subjects who received at least 1 dose of study medication and had at least 1 vital sign parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Pulse Rate | Baseline | 16.0 beats per minute (bpm) | Standard Deviation 7.32 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Pulse Rate | 6 hours | 22.9 beats per minute (bpm) | Standard Deviation 9.1 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Pulse Rate | 12 hours | 12.0 beats per minute (bpm) | Standard Deviation 6.85 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Pulse Rate | Baseline | 14.3 beats per minute (bpm) | Standard Deviation 8.05 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Pulse Rate | 6 hours | 20.4 beats per minute (bpm) | Standard Deviation 8.25 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Pulse Rate | 12 hours | 12.0 beats per minute (bpm) | Standard Deviation 8.6 |
Secondary
Postural Changes in Systolic and Diastolic Blood Pressure
Postural change calculated as position 1 (standing) value minus the position 2 (supine) value. Baseline was the average of 3 predose measurements at each period. Means of replicates were used in calculations.
Time frame: Baseline, 6 and 12 hours post dose on Day 1 from the First Day of each Treatment Leg
Population: The vital sign analysis population was defined as all enrolled subjects who received at least 1 dose of study medication and had at least 1 vital sign parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Baseline | 3.5 mm Hg | Standard Deviation 5.01 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Baseline | 8.9 mm Hg | Standard Deviation 4.69 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: 6 hours | 2.2 mm Hg | Standard Deviation 5.96 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: 6 hours | 8.4 mm Hg | Standard Deviation 4.71 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: 12 hours | 5.9 mm Hg | Standard Deviation 6.21 |
| Maraviroc + Vardenafil (Treatment A) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: 12 hours | 11.4 mm Hg | Standard Deviation 4.66 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: 12 hours | 3.5 mm Hg | Standard Deviation 5.69 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: Baseline | 2.6 mm Hg | Standard Deviation 4.34 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: 6 hours | 9.6 mm Hg | Standard Deviation 4.36 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: Baseline | 7.5 mm Hg | Standard Deviation 3.41 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure: 12 hours | 9.9 mm Hg | Standard Deviation 4.18 |
| Maraviroc + Placebo (Treatment B) | Postural Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure: 6 hours | 1.5 mm Hg | Standard Deviation 5.14 |
Secondary
Standing and Supine Pulse Rate
Supine pulse rate measurement was taken after subject rested for 5 minutes supine. Subject sat for 2 minutes, then stood for 2 minutes and standing measurement taken. Duplicate supine and standing pulse rate measurements taken per protocol. Average of duplicate measurements calculated prior to data analysis.
Time frame: 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours post Vardenafil or Placebo dose
Population: The vital sign analysis population was defined as all enrolled subjects who received at least 1 dose of study medication and had at least 1 vital sign parameter in at least 1 treatment period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 1.5 hours post Maraviroc dose | 85.78 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 2 hours post Maraviroc dose | 85.16 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 2.5 hours post Maraviroc dose | 82.25 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 3 hours post Maraviroc dose | 80.05 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 4 hours post Maraviroc dose | 79.97 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 6 hours post Maraviroc dose | 93.53 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 8 hours post Maraviroc dose | 84.41 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Standing pulse rate: 12 hours post Maraviroc dose | 82.47 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 1.5 hours post Maraviroc dose | 67.56 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 2.5 hours post Maraviroc dose | 61.64 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 3 hours post Maraviroc dose | 60.42 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 4 hours post Maraviroc dose | 60.22 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 6 hours post Maraviroc dose | 71.39 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 8 hours post Maraviroc dose | 67.67 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 12 hours post Maraviroc dose | 71.25 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Vardenafil (Treatment A) | Standing and Supine Pulse Rate | Supine pulse rate: 2 hours post Maraviroc dose | 66.20 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 4 hours post Maraviroc dose | 58.16 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 1.5 hours post Maraviroc dose | 78.45 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 1.5 hours post Maraviroc dose | 60.61 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 2 hours post Maraviroc dose | 78.34 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 2 hours post Maraviroc dose | 60.69 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 2.5 hours post Maraviroc dose | 77.22 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 8 hours post Maraviroc dose | 63.55 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 3 hours post Maraviroc dose | 75.34 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 2.5 hours post Maraviroc dose | 58.00 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 4 hours post Maraviroc dose | 75.92 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 6 hours post Maraviroc dose | 65.94 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 6 hours post Maraviroc dose | 87.17 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 3 hours post Maraviroc dose | 57.53 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 8 hours post Maraviroc dose | 79.34 beats per minute (bpm) | Standard Error 1.6885 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Supine pulse rate: 12 hours post Maraviroc dose | 67.80 beats per minute (bpm) | Standard Error 1.3482 |
| Maraviroc + Placebo (Treatment B) | Standing and Supine Pulse Rate | Standing pulse rate: 12 hours post Maraviroc dose | 80.59 beats per minute (bpm) | Standard Error 1.6885 |
Comparison: 1.5 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [4.18, 9.72]Mixed Models Analysis
Comparison: 2 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [2.73, 8.28]Mixed Models Analysis
Comparison: 2.5 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [0.87, 6.42]Mixed Models Analysis
Comparison: 3 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [0.12, 5.67]Mixed Models Analysis
Comparison: 4 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [-0.71, 4.83]Mixed Models Analysis
Comparison: 6 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [2.68, 8.22]Mixed Models Analysis
Comparison: 8 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [1.34, 6.89]Mixed Models Analysis
Comparison: 12 hour post-dose for supine pulse rate~Vardenafil minus Placebo90% CI: [0.68, 6.22]Mixed Models Analysis
Comparison: 1.5 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [3.7, 10.95]Mixed Models Analysis
Comparison: 2 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [3.2, 10.45]Mixed Models Analysis
Comparison: 2.5 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [1.4, 8.65]Mixed Models Analysis
Comparison: 3 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [1.09, 8.34]Mixed Models Analysis
Comparison: 4 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [0.43, 7.67]Mixed Models Analysis
Comparison: 6 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [2.73, 9.98]Mixed Models Analysis
Comparison: 8 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [1.45, 8.7]Mixed Models Analysis
Comparison: 12 hour post-dose for standing pulse rate~Vardenafil minus Placebo90% CI: [-1.74, 5.51]Mixed Models Analysis