Hypertension
Conditions
Keywords
Clinical Trial, Randomized Controlled Trial, Humans, Cyclic Nucleotide Phosphodiesterases Type 5
Brief summary
The purpose of this study is to evaluate the safety and blood pressure lowering effect of different doses of PF-00489791 in patients with mild to moderate high blood pressure
Interventions
DRUGplacebo
placebo, oral, tablets, once daily, for 28 days
DRUGPF-00489791
PF-00489791 20 mg titrated to 40 mg, oral, tablets, once daily, for 28 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and/or Females of non-childbearing potential between 18 and 70 years of age 2. History of mild to moderate hypertension
Exclusion criteria
1. Type 1 or 2 diabetes on prescribed medications 2. Secondary, severe, or malignant hypertension 3. History of a significant cardiovascular event within the last 12 months of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime SBP was an average of SBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime SBP at Day 28 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean 24-hour SBP and DBP was an average of SBP and DBP measurements, respectively, taken for 24 hours by ABPM device respectively. In this outcome measure change from baseline in mean 24-hour SBP and DBP at Day 28 is reported. |
| Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug), Day 1, 14 and 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed on Baseline, Day 1, 14 and 28. In this outcome measure maximum and minimum SBP and DBP values recorded by ABPM device over 24 hours on Baseline, Day 1, 14 and 28 are reported. |
| Change From Baseline in Cuff SBP and DBP at Day 28 | Baseline (pre dose value on Day 1 of treatment), Day 28 | At Baseline and Day 28 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. |
| Change From Baseline in Cuff SBP and DBP at Day 31 | Baseline (pre dose value on Day 1 of treatment), Day 31 | At Baseline and Day 31 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. |
| Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28 | The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime DBP was an average of DBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime DBP at Day 28 is reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | Criteria for laboratory abnormalities included: hemoglobin, hematocrit, red blood cell count, total neutrophils, total protein, albumin: \<0.8\* limit of normal (LLN). Platelets: less than (\<)0.5\* LLN, greater than (\>)1.75\* upper limit of normal (ULN); white blood cell, glucose: \<0.6\*LLN, \>1.5\*ULN, lymphocytes: \<0.8\*LLN; \>1.2\*ULN; basophils, monocytes, eosinophils, total protein, albumin, uric acid: \>1.2\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>3.0\*ULN; blood urea nitrogen, creatinine: \>1.3\*ULN; sodium: \<0.95\*LLN, \>1.05\*ULN; potassium, chloride, calcium: \<0.9\*LLN, \>1.1\*ULN; creatine kinase: \> 2.0\*ULN, \> 3.0\*ULN, \>10.0\*ULN; total bilirubin, direct bilirubin, indirect bilirubin:\>1.5\*ULN; urinalysis: urine pH: \<4.5, \>8, glucose, ketones, protein, blood/hemoglobin: \>=1, RBC, WBC, epithelial cells: \>=6, casts: \>1, bacteria: \>20. |
| Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Baseline (pre dose value on Day 1 of treatment), Day 1, 7, 14, 21, 28, 31 | Sitting heart rate was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the heart rate was measured. The heart rate was measured for a minimum of 30 seconds, and the average of two measurements was recorded. Heart rate was measured in beats per minute. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) | Following ECG parameters were evaluated: QT interval, QTc interval, RR interval, PR interval, QRS complex and heart rate. Clinical significant ECG findings were determined by the investigator's discretion. |
| Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | Baseline (pre dose value on Day 1 of treatment), Day 28 | At Baseline and Day 28, sitting cuff MAP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first MAP was obtained. The MAP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded. |
Countries
United States
Participant flow
Pre-assignment details
A total of 426 participants were screened, of whom 291 participants were screen failed and 135 participants were enrolled in the study and assigned to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with mild to moderate hypertension were randomized to receive placebo orally, once daily for 28 days. Participants were followed up to maximum of 14 days after the last dose. | 34 |
| PF-00489791 4 mg Participants with mild to moderate hypertension were randomized to receive PF-00489791 4 mg (2 tablets of 2 mg) orally, once daily for 28 days. Participants were followed up to maximum of 14 days after the last dose. | 34 |
| PF-00489791 10 mg Participants with mild to moderate hypertension were randomized to receive PF-00489791 10 mg tablet orally, once daily for 28 days. Participants were followed up to maximum of 14 days after the last dose. | 32 |
| PF-00489791 20/40 mg Participants with mild to moderate hypertension were randomized to receive PF-00489791 20 mg (2 tablets of 10 mg) orally, once daily for 14 days and then 40 mg (4 tablets of 10 mg) orally once daily for next 14 days. Participants were followed up to maximum of 14 days after the last dose. | 33 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 1 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 2 |
| Overall Study | Participants no longer willing to participate in study | 1 | 0 | 0 | 0 |
| Overall Study | Randomized but not treated | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | PF-00489791 4 mg | PF-00489791 10 mg | PF-00489791 20/40 mg | Total |
|---|---|---|---|---|---|
| Age, Customized 18-44 years | 2 Participants | 1 Participants | 2 Participants | 6 Participants | 11 Participants |
| Age, Customized 45-64 years | 28 Participants | 27 Participants | 26 Participants | 23 Participants | 104 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 4 Participants | 6 Participants | 4 Participants | 4 Participants | 18 Participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 13 Participants | 10 Participants | 49 Participants |
| Sex: Female, Male Male | 20 Participants | 22 Participants | 19 Participants | 23 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 34 | 0 / 32 | 0 / 33 |
| other Total, other adverse events | 12 / 34 | 11 / 34 | 11 / 32 | 13 / 33 |
| serious Total, serious adverse events | 1 / 34 | 1 / 34 | 0 / 32 | 0 / 33 |
Outcome results
Primary
Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28
The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime SBP was an average of SBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime SBP at Day 28 is reported.
Time frame: From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | 1.38 millimeter of mercury | Standard Error 1.55 |
| PF-00489791 4 mg | Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | -1.42 millimeter of mercury | Standard Error 1.12 |
| PF-00489791 10 mg | Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | -3.28 millimeter of mercury | Standard Error 1.08 |
| PF-00489791 20/40 mg | Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) as Measured by Ambulatory Blood Pressure Monitoring (ABPM) at Day 28 | -5.59 millimeter of mercury | Standard Error 1.54 |
p-value: 0.082295% CI: [-5.97, 0.36]Nonlinear dose response regression model
p-value: 0.01795% CI: [-8.47, -0.85]Nonlinear dose response regression model
p-value: 0.002695% CI: [-11.45, -2.48]Nonlinear dose response regression model
Secondary
Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28
At Baseline and Day 28, sitting cuff MAP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first MAP was obtained. The MAP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded.
Time frame: Baseline (pre dose value on Day 1 of treatment), Day 28
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | -2.59 millimeter of mercury | Standard Error 1.29 |
| PF-00489791 4 mg | Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | -4.54 millimeter of mercury | Standard Error 1.26 |
| PF-00489791 10 mg | Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | -5.53 millimeter of mercury | Standard Error 1.31 |
| PF-00489791 20/40 mg | Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28 | -7.06 millimeter of mercury | Standard Error 1.34 |
p-value: 0.256795% CI: [-5.32, 1.44]ANCOVA
p-value: 0.08695% CI: [-6.29, 0.42]ANCOVA
p-value: 0.010395% CI: [-7.85, -1.08]ANCOVA
Secondary
Change From Baseline in Cuff SBP and DBP at Day 28
At Baseline and Day 28 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded.
Time frame: Baseline (pre dose value on Day 1 of treatment), Day 28
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff SBP | -4.60 millimeter of mercury | Standard Error 1.88 |
| Placebo | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff DBP | -1.33 millimeter of mercury | Standard Error 1.27 |
| PF-00489791 4 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff DBP | -4.37 millimeter of mercury | Standard Error 1.22 |
| PF-00489791 4 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff SBP | -5.20 millimeter of mercury | Standard Error 1.82 |
| PF-00489791 10 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff SBP | -4.97 millimeter of mercury | Standard Error 1.89 |
| PF-00489791 10 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff DBP | -5.82 millimeter of mercury | Standard Error 1.27 |
| PF-00489791 20/40 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff SBP | -9.76 millimeter of mercury | Standard Error 1.95 |
| PF-00489791 20/40 mg | Change From Baseline in Cuff SBP and DBP at Day 28 | Cuff DBP | -5.63 millimeter of mercury | Standard Error 1.3 |
Comparison: For cuff SBPp-value: 0.809195% CI: [-5.51, 4.31]ANCOVA
Comparison: For cuff SBPp-value: 0.880995% CI: [-5.21, 4.48]ANCOVA
Comparison: For cuff SBPp-value: 0.038295% CI: [-10.04, -0.29]ANCOVA
Comparison: For cuff DBPp-value: 0.073195% CI: [-6.35, 0.29]ANCOVA
Comparison: For cuff DBPp-value: 0.007795% CI: [-7.77, -1.22]ANCOVA
Comparison: For cuff DBPp-value: 0.011195% CI: [-7.58, -1]ANCOVA
Secondary
Change From Baseline in Cuff SBP and DBP at Day 31
At Baseline and Day 31 visit, sitting cuff SBP and DBP was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the first BP was obtained. The BP measurement was done in duplicate approximately 5 minutes apart. The mean of duplicate measurements was recorded.
Time frame: Baseline (pre dose value on Day 1 of treatment), Day 31
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff SBP | 0.4 millimeter of mercury | Standard Deviation 10.18 |
| Placebo | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff DBP | -0.7 millimeter of mercury | Standard Deviation 6.76 |
| PF-00489791 4 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff DBP | -0.2 millimeter of mercury | Standard Deviation 7.47 |
| PF-00489791 4 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff SBP | -0.6 millimeter of mercury | Standard Deviation 11.39 |
| PF-00489791 10 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff SBP | -0.3 millimeter of mercury | Standard Deviation 10.96 |
| PF-00489791 10 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff DBP | -0.8 millimeter of mercury | Standard Deviation 7.58 |
| PF-00489791 20/40 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff SBP | 0.4 millimeter of mercury | Standard Deviation 13.07 |
| PF-00489791 20/40 mg | Change From Baseline in Cuff SBP and DBP at Day 31 | Cuff DBP | 0.3 millimeter of mercury | Standard Deviation 7.86 |
Secondary
Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31
Sitting heart rate was measured with the participant's arm supported at the level of the heart. The participant sat with feet flat on the floor for 5 minutes before the heart rate was measured. The heart rate was measured for a minimum of 30 seconds, and the average of two measurements was recorded. Heart rate was measured in beats per minute.
Time frame: Baseline (pre dose value on Day 1 of treatment), Day 1, 7, 14, 21, 28, 31
Population: FAS included all randomized subjects who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, number analyzed signifies participants evaluable at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Baseline | 71.5 Beats per minute | Standard Deviation 8.76 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 21 | 0.5 Beats per minute | Standard Deviation 7.27 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 14 | -1.2 Beats per minute | Standard Deviation 5.35 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 31 | -1.4 Beats per minute | Standard Deviation 8.85 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 7 | -0.3 Beats per minute | Standard Deviation 5.92 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day1 | 0.5 Beats per minute | Standard Deviation 6.04 |
| Placebo | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 28 | -0.0 Beats per minute | Standard Deviation 7.77 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 21 | 2.9 Beats per minute | Standard Deviation 9.18 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 7 | 1.5 Beats per minute | Standard Deviation 7.44 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 31 | -0.3 Beats per minute | Standard Deviation 8.17 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 14 | -0.1 Beats per minute | Standard Deviation 8.08 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day1 | 1.8 Beats per minute | Standard Deviation 6.64 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Baseline | 69.2 Beats per minute | Standard Deviation 8.43 |
| PF-00489791 4 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 28 | 0.5 Beats per minute | Standard Deviation 7.78 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Baseline | 67.9 Beats per minute | Standard Deviation 8.63 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day1 | 4.8 Beats per minute | Standard Deviation 7.42 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 7 | 3.2 Beats per minute | Standard Deviation 9.6 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 14 | 1.6 Beats per minute | Standard Deviation 8.23 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 21 | -0.3 Beats per minute | Standard Deviation 8.55 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 28 | 0.8 Beats per minute | Standard Deviation 9.31 |
| PF-00489791 10 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 31 | 0.7 Beats per minute | Standard Deviation 8.76 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 21 | 4.9 Beats per minute | Standard Deviation 8.7 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 31 | 4.8 Beats per minute | Standard Deviation 8.26 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 28 | 3.4 Beats per minute | Standard Deviation 9.38 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day1 | 5.7 Beats per minute | Standard Deviation 8.14 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 7 | 4.6 Beats per minute | Standard Deviation 8.47 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Change at Day 14 | 4.0 Beats per minute | Standard Deviation 7.15 |
| PF-00489791 20/40 mg | Change From Baseline in Heart Rate at Baseline, Day 1, 7, 14, 21, 28 and 31 | Baseline | 68.3 Beats per minute | Standard Deviation 7.9 |
Secondary
Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28
The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean 24-hour SBP and DBP was an average of SBP and DBP measurements, respectively, taken for 24 hours by ABPM device respectively. In this outcome measure change from baseline in mean 24-hour SBP and DBP at Day 28 is reported.
Time frame: Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | SBP | -0.53 millimeter of mercury | Standard Error 1.53 |
| Placebo | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | DBP | -0.13 millimeter of mercury | Standard Error 1.07 |
| PF-00489791 4 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | DBP | -1.58 millimeter of mercury | Standard Error 1.07 |
| PF-00489791 4 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | SBP | -0.40 millimeter of mercury | Standard Error 1.47 |
| PF-00489791 10 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | SBP | -5.28 millimeter of mercury | Standard Error 1.55 |
| PF-00489791 10 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | DBP | -3.94 millimeter of mercury | Standard Error 1.09 |
| PF-00489791 20/40 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | SBP | -3.96 millimeter of mercury | Standard Error 1.57 |
| PF-00489791 20/40 mg | Change From Baseline in Mean 24-Hour SBP and DBP as Measured by ABPM at Day 28 | DBP | -4.09 millimeter of mercury | Standard Error 1.09 |
Comparison: For SBPp-value: 0.947995% CI: [-3.79, 4.05]ANCOVA
Comparison: For SBPp-value: 0.021595% CI: [-8.78, -0.72]ANCOVA
Comparison: For SBPp-value: 0.088695% CI: [-7.39, 0.53]ANCOVA
Comparison: For DBPp-value: 0.317395% CI: [-4.3, 1.41]ANCOVA
Comparison: For DBPp-value: 0.008795% CI: [-6.64, -0.99]ANCOVA
Comparison: For DBPp-value: 0.006295% CI: [-6.76, -1.15]ANCOVA
Secondary
Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28
The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed in this study on Baseline, Day 1, 14 and 28. Mean daytime DBP was an average of DBP measurements taken between 08:00 and 16:00 hours by ABPM device on the specified time points. In this outcome measure change from baseline in mean daytime DBP at Day 28 is reported.
Time frame: From 08:00 to 16:00 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug) and Day 28
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | 0.73 millimeter of mercury | Standard Error 1.09 |
| PF-00489791 4 mg | Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | -1.97 millimeter of mercury | Standard Error 0.81 |
| PF-00489791 10 mg | Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | -3.83 millimeter of mercury | Standard Error 0.78 |
| PF-00489791 20/40 mg | Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) as Measured by ABPM at Day 28 | -6.23 millimeter of mercury | Standard Error 1.09 |
p-value: 0.026495% CI: [-5.09, -0.32]Nonlinear dose response regression model
p-value: 0.001695% CI: [-7.35, -1.77]Nonlinear dose response regression model
p-value: <0.000195% CI: [-10.03, -3.89]Nonlinear dose response regression model
Secondary
Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28
The ABPM device was automatically programmed to inflate at every 20 minutes from 05:00 until 21:59 hours and from 22:00 to 04:59 hours the device inflated every 60 minutes. 24-hour clock time was used. ABPM was performed on Baseline, Day 1, 14 and 28. In this outcome measure maximum and minimum SBP and DBP values recorded by ABPM device over 24 hours on Baseline, Day 1, 14 and 28 are reported.
Time frame: Over 24 hours on Baseline (Day 0, 1 day prior to first double-blind dose of study drug), Day 1, 14 and 28
Population: FAS included all randomized participants who received at least 1 dose of study medication and had a valid baseline and at least 1 valid post-baseline assessment of the primary endpoint. Here, number analyzed signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 14 | 177.58 millimeter of mercury | Standard Deviation 14.53 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Baseline | 176.65 millimeter of mercury | Standard Deviation 12.38 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 1 | 173.13 millimeter of mercury | Standard Deviation 12.21 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 28 | 177.33 millimeter of mercury | Standard Deviation 14.54 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Baseline | 117.88 millimeter of mercury | Standard Deviation 11.79 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 1 | 119.06 millimeter of mercury | Standard Deviation 12.32 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 14 | 113.82 millimeter of mercury | Standard Deviation 12.76 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 28 | 117.57 millimeter of mercury | Standard Deviation 15.54 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Baseline | 116.21 millimeter of mercury | Standard Deviation 7.01 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 1 | 113.81 millimeter of mercury | Standard Deviation 8.13 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 14 | 115.03 millimeter of mercury | Standard Deviation 9.17 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 28 | 117.20 millimeter of mercury | Standard Deviation 11.86 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Baseline | 68.15 millimeter of mercury | Standard Deviation 9.08 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 1 | 67.69 millimeter of mercury | Standard Deviation 9.3 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 14 | 65.48 millimeter of mercury | Standard Deviation 9.15 |
| Placebo | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 28 | 65.93 millimeter of mercury | Standard Deviation 11.58 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Baseline | 114.38 millimeter of mercury | Standard Deviation 12.65 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Baseline | 114.53 millimeter of mercury | Standard Deviation 10.53 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 14 | 177.90 millimeter of mercury | Standard Deviation 21.59 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Baseline | 63.50 millimeter of mercury | Standard Deviation 8.31 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 14 | 62.07 millimeter of mercury | Standard Deviation 9.51 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 1 | 110.58 millimeter of mercury | Standard Deviation 10.29 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 28 | 180.40 millimeter of mercury | Standard Deviation 19.4 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 28 | 113.10 millimeter of mercury | Standard Deviation 9.42 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 14 | 114.31 millimeter of mercury | Standard Deviation 13.59 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 14 | 111.97 millimeter of mercury | Standard Deviation 10.61 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 1 | 60.67 millimeter of mercury | Standard Deviation 8.86 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 1 | 176.67 millimeter of mercury | Standard Deviation 19.6 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 28 | 62.23 millimeter of mercury | Standard Deviation 7.78 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 28 | 114.27 millimeter of mercury | Standard Deviation 13.66 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 1 | 110.27 millimeter of mercury | Standard Deviation 14.38 |
| PF-00489791 4 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Baseline | 179.68 millimeter of mercury | Standard Deviation 12.4 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Baseline | 184.58 millimeter of mercury | Standard Deviation 15.3 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Baseline | 122.52 millimeter of mercury | Standard Deviation 11.66 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 1 | 110.21 millimeter of mercury | Standard Deviation 13.46 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 1 | 59.34 millimeter of mercury | Standard Deviation 8.52 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 14 | 114.07 millimeter of mercury | Standard Deviation 11.99 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 28 | 116.64 millimeter of mercury | Standard Deviation 10.28 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 28 | 64.11 millimeter of mercury | Standard Deviation 8.71 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Baseline | 116.81 millimeter of mercury | Standard Deviation 11.97 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 1 | 111.38 millimeter of mercury | Standard Deviation 9.63 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 14 | 61.13 millimeter of mercury | Standard Deviation 9.75 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 14 | 111.97 millimeter of mercury | Standard Deviation 10.35 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 28 | 112.32 millimeter of mercury | Standard Deviation 11.76 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Baseline | 67.90 millimeter of mercury | Standard Deviation 9.01 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 1 | 175.62 millimeter of mercury | Standard Deviation 12.29 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 14 | 179.60 millimeter of mercury | Standard Deviation 11.75 |
| PF-00489791 10 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 28 | 177.04 millimeter of mercury | Standard Deviation 14.29 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 28 | 61.38 millimeter of mercury | Standard Deviation 8.42 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Baseline | 116.76 millimeter of mercury | Standard Deviation 9.86 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 28 | 110.34 millimeter of mercury | Standard Deviation 8.32 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 1 | 60.16 millimeter of mercury | Standard Deviation 8.6 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Baseline | 177.45 millimeter of mercury | Standard Deviation 15.42 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Baseline | 65.18 millimeter of mercury | Standard Deviation 8.11 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 14 | 111.94 millimeter of mercury | Standard Deviation 10.52 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Baseline | 115.30 millimeter of mercury | Standard Deviation 13.6 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 1 | 168.00 millimeter of mercury | Standard Deviation 12.17 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum SBP: Day 1 | 109.38 millimeter of mercury | Standard Deviation 13.3 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 28 | 174.69 millimeter of mercury | Standard Deviation 12.14 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 14 | 111.58 millimeter of mercury | Standard Deviation 10.09 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Minimum DBP: Day 14 | 62.45 millimeter of mercury | Standard Deviation 8.2 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 1 | 109.41 millimeter of mercury | Standard Deviation 11.16 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum SBP: Day 14 | 176.52 millimeter of mercury | Standard Deviation 16.68 |
| PF-00489791 20/40 mg | Minimum and Maximum SBP and DBP as Measured by ABPM Over 24 Hours on Baseline, Day 1, 14 and 28 | Maximum DBP: Day 28 | 111.97 millimeter of mercury | Standard Deviation 10.58 |
Secondary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
Following ECG parameters were evaluated: QT interval, QTc interval, RR interval, PR interval, QRS complex and heart rate. Clinical significant ECG findings were determined by the investigator's discretion.
Time frame: Day 1 up to 14 days after last dose of study drug (maximum up to 42 days)
Population: Safety analysis set included all participants who took at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 1 Participants |
| PF-00489791 4 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| PF-00489791 10 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| PF-00489791 20/40 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Criteria for laboratory abnormalities included: hemoglobin, hematocrit, red blood cell count, total neutrophils, total protein, albumin: \<0.8\* limit of normal (LLN). Platelets: less than (\<)0.5\* LLN, greater than (\>)1.75\* upper limit of normal (ULN); white blood cell, glucose: \<0.6\*LLN, \>1.5\*ULN, lymphocytes: \<0.8\*LLN; \>1.2\*ULN; basophils, monocytes, eosinophils, total protein, albumin, uric acid: \>1.2\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: \>3.0\*ULN; blood urea nitrogen, creatinine: \>1.3\*ULN; sodium: \<0.95\*LLN, \>1.05\*ULN; potassium, chloride, calcium: \<0.9\*LLN, \>1.1\*ULN; creatine kinase: \> 2.0\*ULN, \> 3.0\*ULN, \>10.0\*ULN; total bilirubin, direct bilirubin, indirect bilirubin:\>1.5\*ULN; urinalysis: urine pH: \<4.5, \>8, glucose, ketones, protein, blood/hemoglobin: \>=1, RBC, WBC, epithelial cells: \>=6, casts: \>1, bacteria: \>20.
Time frame: Day 1 up to 14 days after last dose of study drug (maximum up to 42 days)
Population: Safety analysis set included all participants who took at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 10 Participants |
| PF-00489791 4 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 9 Participants |
| PF-00489791 10 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 11 Participants |
| PF-00489791 20/40 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 10 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Time frame: Day 1 up to 14 days after last dose of study drug (maximum up to 42 days)
Population: Safety analysis set included all participants who took at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 12 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| PF-00489791 4 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| PF-00489791 4 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| PF-00489791 10 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| PF-00489791 10 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| PF-00489791 20/40 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 13 Participants |
| PF-00489791 20/40 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |