Trial Outcomes & Findings for A Dose Finding Study Of PF-00489791 In Patients With Mild To Moderate High Blood Pressure (NCT NCT00422461)

Last Updated: 2021-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

135 participants

Primary outcome timeframe

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

Results posted on

2021-10-11

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	PF-00489791 4 mg Participants with mild to moderate hypertension were randomized to receive PF-00489791 4 milligram (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.	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.	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.
Overall Study STARTED	35	35	32	33
Overall Study Treated	34	34	32	33
Overall Study Full Analysis Set	34	34	31	33
Overall Study COMPLETED	32	32	31	30
Overall Study NOT COMPLETED	3	3	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	PF-00489791 4 mg Participants with mild to moderate hypertension were randomized to receive PF-00489791 4 milligram (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.	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.	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.
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

A Dose Finding Study Of PF-00489791 In Patients With Mild To Moderate High Blood Pressure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=32 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.	Total n=133 Participants Total of all reporting groups
Age, Customized 18-44 years	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	11 Participants n=21 Participants
Age, Customized 45-64 years	28 Participants n=5 Participants	27 Participants n=7 Participants	26 Participants n=5 Participants	23 Participants n=4 Participants	104 Participants n=21 Participants
Age, Customized Greater than or equal to (>=) 65 years	4 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	18 Participants n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	10 Participants n=4 Participants	49 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	22 Participants n=7 Participants	19 Participants n=5 Participants	23 Participants n=4 Participants	84 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	PF-00489791 4 mg n=30 Participants 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.	PF-00489791 10 mg n=30 Participants 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.	PF-00489791 20/40 mg n=30 Participants 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.
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	-1.42 millimeter of mercury Standard Error 1.12	-3.28 millimeter of mercury Standard Error 1.08	-5.59 millimeter of mercury Standard Error 1.54

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants 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.	PF-00489791 4 mg n=30 Participants 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.	PF-00489791 10 mg n=30 Participants 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.	PF-00489791 20/40 mg n=30 Participants 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.
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	-1.97 millimeter of mercury Standard Error 0.81	-3.83 millimeter of mercury Standard Error 0.78	-6.23 millimeter of mercury Standard Error 1.09

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants 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.	PF-00489791 4 mg n=30 Participants 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.	PF-00489791 10 mg n=28 Participants 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.	PF-00489791 20/40 mg n=29 Participants 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.
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	-0.40 millimeter of mercury Standard Error 1.47	-5.28 millimeter of mercury Standard Error 1.55	-3.96 millimeter of mercury Standard Error 1.57
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	-1.58 millimeter of mercury Standard Error 1.07	-3.94 millimeter of mercury Standard Error 1.09	-4.09 millimeter of mercury Standard Error 1.09

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants 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.	PF-00489791 4 mg n=31 Participants 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.	PF-00489791 10 mg n=31 Participants 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.	PF-00489791 20/40 mg n=30 Participants 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.
Change From Baseline in Cuff SBP and DBP at Day 28 Cuff SBP	-4.60 millimeter of mercury Standard Error 1.88	-5.20 millimeter of mercury Standard Error 1.82	-4.97 millimeter of mercury Standard Error 1.89	-9.76 millimeter of mercury Standard Error 1.95
Change From Baseline in Cuff SBP and DBP at Day 28 Cuff DBP	-1.33 millimeter of mercury Standard Error 1.27	-4.37 millimeter of mercury Standard Error 1.22	-5.82 millimeter of mercury Standard Error 1.27	-5.63 millimeter of mercury Standard Error 1.30

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=31 Participants 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.	PF-00489791 20/40 mg n=32 Participants 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.
Change From Baseline in Cuff SBP and DBP at Day 31 Cuff SBP	0.4 millimeter of mercury Standard Deviation 10.18	-0.6 millimeter of mercury Standard Deviation 11.39	-0.3 millimeter of mercury Standard Deviation 10.96	0.4 millimeter of mercury Standard Deviation 13.07
Change From Baseline in Cuff SBP and DBP at Day 31 Cuff DBP	-0.7 millimeter of mercury Standard Deviation 6.76	-0.2 millimeter of mercury Standard Deviation 7.47	-0.8 millimeter of mercury Standard Deviation 7.58	0.3 millimeter of mercury Standard Deviation 7.86

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants 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.	PF-00489791 4 mg n=31 Participants 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.	PF-00489791 10 mg n=31 Participants 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.	PF-00489791 20/40 mg n=30 Participants 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.
Change From Baseline in Cuff Mean Arterial Pressure (MAP) at Day 28	-2.59 millimeter of mercury Standard Error 1.29	-4.54 millimeter of mercury Standard Error 1.26	-5.53 millimeter of mercury Standard Error 1.31	-7.06 millimeter of mercury Standard Error 1.34

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=32 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	12 Participants	11 Participants	11 Participants	13 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=32 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.
Number of Participants With Clinically Significant Laboratory Abnormalities	10 Participants	9 Participants	11 Participants	10 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=31 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.
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	69.2 Beats per minute Standard Deviation 8.43	67.9 Beats per minute Standard Deviation 8.63	68.3 Beats per minute Standard Deviation 7.90
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	1.8 Beats per minute Standard Deviation 6.64	4.8 Beats per minute Standard Deviation 7.42	5.7 Beats per minute Standard Deviation 8.14
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	1.5 Beats per minute Standard Deviation 7.44	3.2 Beats per minute Standard Deviation 9.60	4.6 Beats per minute Standard Deviation 8.47
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	-0.1 Beats per minute Standard Deviation 8.08	1.6 Beats per minute Standard Deviation 8.23	4.0 Beats per minute Standard Deviation 7.15
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	2.9 Beats per minute Standard Deviation 9.18	-0.3 Beats per minute Standard Deviation 8.55	4.9 Beats per minute Standard Deviation 8.70
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	0.5 Beats per minute Standard Deviation 7.78	0.8 Beats per minute Standard Deviation 9.31	3.4 Beats per minute Standard Deviation 9.38
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	-0.3 Beats per minute Standard Deviation 8.17	0.7 Beats per minute Standard Deviation 8.76	4.8 Beats per minute Standard Deviation 8.26

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=32 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings	1 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

PF-00489791 4 mg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

PF-00489791 10 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

PF-00489791 20/40 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=34 participants at risk 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.	PF-00489791 4 mg n=34 participants at risk 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.	PF-00489791 10 mg n=32 participants at risk 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.	PF-00489791 20/40 mg n=33 participants at risk 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.
Psychiatric disorders Post-traumatic stress disorder	0.00% 0/34 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	2.9% 1/34 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	0.00% 0/32 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	0.00% 0/33 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.
Gastrointestinal disorders Stomach discomfort	2.9% 1/34 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	0.00% 0/34 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	0.00% 0/32 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.	0.00% 0/33 • Day 1 up to 14 days after last dose of study drug (maximum up to 42 days) Same event may appear as both an adverse events (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all participants who took at least 1 dose of study drug.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER

Measure	Placebo n=34 Participants 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.	PF-00489791 4 mg n=34 Participants 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.	PF-00489791 10 mg n=31 Participants 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.	PF-00489791 20/40 mg n=33 Participants 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.
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	176.67 millimeter of mercury Standard Deviation 19.60	175.62 millimeter of mercury Standard Deviation 12.29	168.00 millimeter of mercury Standard Deviation 12.17
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	179.68 millimeter of mercury Standard Deviation 12.40	184.58 millimeter of mercury Standard Deviation 15.30	177.45 millimeter of mercury Standard Deviation 15.42
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	177.90 millimeter of mercury Standard Deviation 21.59	179.60 millimeter of mercury Standard Deviation 11.75	176.52 millimeter of mercury Standard Deviation 16.68
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	180.40 millimeter of mercury Standard Deviation 19.40	177.04 millimeter of mercury Standard Deviation 14.29	174.69 millimeter of mercury Standard Deviation 12.14
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	114.38 millimeter of mercury Standard Deviation 12.65	122.52 millimeter of mercury Standard Deviation 11.66	115.30 millimeter of mercury Standard Deviation 13.60
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	110.27 millimeter of mercury Standard Deviation 14.38	110.21 millimeter of mercury Standard Deviation 13.46	109.38 millimeter of mercury Standard Deviation 13.30
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	114.31 millimeter of mercury Standard Deviation 13.59	114.07 millimeter of mercury Standard Deviation 11.99	111.94 millimeter of mercury Standard Deviation 10.52
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	114.27 millimeter of mercury Standard Deviation 13.66	116.64 millimeter of mercury Standard Deviation 10.28	110.34 millimeter of mercury Standard Deviation 8.32
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	114.53 millimeter of mercury Standard Deviation 10.53	116.81 millimeter of mercury Standard Deviation 11.97	116.76 millimeter of mercury Standard Deviation 9.86
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	110.58 millimeter of mercury Standard Deviation 10.29	111.38 millimeter of mercury Standard Deviation 9.63	109.41 millimeter of mercury Standard Deviation 11.16
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	111.97 millimeter of mercury Standard Deviation 10.61	111.97 millimeter of mercury Standard Deviation 10.35	111.58 millimeter of mercury Standard Deviation 10.09
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	113.10 millimeter of mercury Standard Deviation 9.42	112.32 millimeter of mercury Standard Deviation 11.76	111.97 millimeter of mercury Standard Deviation 10.58
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	63.50 millimeter of mercury Standard Deviation 8.31	67.90 millimeter of mercury Standard Deviation 9.01	65.18 millimeter of mercury Standard Deviation 8.11
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 9.30	60.67 millimeter of mercury Standard Deviation 8.86	59.34 millimeter of mercury Standard Deviation 8.52	60.16 millimeter of mercury Standard Deviation 8.60
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	62.07 millimeter of mercury Standard Deviation 9.51	61.13 millimeter of mercury Standard Deviation 9.75	62.45 millimeter of mercury Standard Deviation 8.20
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	62.23 millimeter of mercury Standard Deviation 7.78	64.11 millimeter of mercury Standard Deviation 8.71	61.38 millimeter of mercury Standard Deviation 8.42