Trial Outcomes & Findings for A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease (NCT NCT00930059)

Last Updated: 2020-11-19

Results Overview

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

191 participants

Primary outcome timeframe

Baseline (Day 1)

Results posted on

2020-11-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Overall Study STARTED	100	91
Overall Study COMPLETED	92	79
Overall Study NOT COMPLETED	8	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Overall Study Death	1	0
Overall Study Did not meet entrance criteria	1	1
Overall Study Withdrawal by Subject	3	4
Overall Study Other	1	0
Overall Study 1 site terminated by sponsor	1	1
Overall Study Adverse Event	1	6

Baseline Characteristics

A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.	Total n=191 Participants Total of all reporting groups
Age, Continuous	73.5 years STANDARD_DEVIATION 7.5 • n=93 Participants	73.6 years STANDARD_DEVIATION 8.2 • n=4 Participants	73.5 years STANDARD_DEVIATION 7.8 • n=27 Participants
Sex: Female, Male Female	64 Participants n=93 Participants	58 Participants n=4 Participants	122 Participants n=27 Participants
Sex: Female, Male Male	36 Participants n=93 Participants	33 Participants n=4 Participants	69 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1)

Population: FAS included all participants who consumed at least 1 dose of randomized study medication.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline	21.87 units on a scale Standard Deviation 10.42	22.66 units on a scale Standard Deviation 10.39

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=80 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 12	-1.60 units on a scale Standard Error 0.50	-1.91 units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline, Week 3, 6, 9

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. "Number analyzed" signifies those participants who were evaluable for this measure at the specified time points for each arm, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 Change at Week 3	-1.36 units on a scale Standard Error 0.49	-1.16 units on a scale Standard Error 0.52
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 Change at Week 6	-1.17 units on a scale Standard Error 0.50	-1.53 units on a scale Standard Error 0.53
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 Change at Week 9	-2.05 units on a scale Standard Error 0.50	-2.68 units on a scale Standard Error 0.53

SECONDARY outcome

Timeframe: Week 3, 6, 9, 12

Population: FAS included all participants who consumed at least 1 dose of randomized study medication. "Number Analyzed" signifies those participants who were evaluable for this measure at the specified time points for each arm, respectively.

CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Clinical Global Impression - Improvement (CGI-I) Week 6	3.51 units on a scale Standard Error 0.10	3.58 units on a scale Standard Error 0.11
Clinical Global Impression - Improvement (CGI-I) Week 9	3.63 units on a scale Standard Error 0.10	3.45 units on a scale Standard Error 0.11
Clinical Global Impression - Improvement (CGI-I) Week 12	3.53 units on a scale Standard Error 0.10	3.32 units on a scale Standard Error 0.11
Clinical Global Impression - Improvement (CGI-I) Week 3	3.64 units on a scale Standard Error 0.10	3.70 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline

Population: FAS included all participants who consumed at least 1 dose of randomized study medication.

NPI total score evaluates disturbances in 12 behavioral domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating and night time behavior. NPI total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater behavioral disturbances.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Neuropsychiatric Inventory (NPI) Total Score at Baseline	12.16 units on a scale Standard Deviation 12.86	10.67 units on a scale Standard Deviation 11.28

SECONDARY outcome

Timeframe: Baseline, Week 3, 6, 9, 12

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 Change at Week 3	-2.02 units on a scale Standard Error 0.66	-1.33 units on a scale Standard Error 0.70
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 Change at Week 12	-2.70 units on a scale Standard Error 0.67	-2.86 units on a scale Standard Error 0.72
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 Change at Week 6	-2.61 units on a scale Standard Error 0.66	-1.76 units on a scale Standard Error 0.71
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 Change at Week 9	-3.44 units on a scale Standard Error 0.66	-2.49 units on a scale Standard Error 0.72

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 12

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure.

Criteria for laboratory test abnormality: a) Hematology: white blood cells (WBC) \<0.6\*lower limit of normal (LLN)/\>1.5\*upper limit of normal (ULN), hemoglobin, hematocrit, red blood cells (RBC), lymphocytes \<0.8\*LLN, total neutrophils \<0.8\*LLN/ \>1.2\*ULN, basophils, eosinophils, monocytes \>1.2\*ULN; b) Liver Function: total bilirubin \>1.5\*ULN, aspartate aminotransferase (AT), alanine AT\[\>0.3\*ULN, total protein, albumin \<0.8\*LLN/ \>1.2\*ULN; c) Renal Function: creatinine \>1.3\*ULN, uric acid \>1.2\*ULN; d) Electrolytes: sodium \<0.95\*LLN/ \>1.05\*ULN, potassium, chloride, bicarbonate \<0.9\*LLN/ \>1.1\*ULN; e) Clinical Chemistry: glucose \<0.6\*LLN/ \>1.5\*ULN, glycosylated hemoglobin \>1.3\*ULN; f) Urinalysis: ketones, protein, blood/hemoglobin, urine glucose \>=1, RBC, WBC \>=6, hyaline casts \>1; g) Hormones: tetraiodothyronine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) \<0.8\*LLN/1.2\*ULN.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=88 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Number of Participants With Laboratory Test Abnormalities	33 Participants	28 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 12

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. Here, "Number Analyzed" signifies those participants who were evaluable for specified rows for each arm, respectively.

Criteria for ECG (12-lead) abnormalities were as follow: 1) PR interval: greater than and equal to (\>=) 300 milliseconds (msec), 2) PR interval: maximum increase from baseline \>=25 percent (%) (if baseline PR interval greater than \[\>\] 100 msec) or \>=50% (if baseline PR interval less than or equal to \[\<=\] 100 msec); 3) QRS complex: \>=200 msec, 4) QRS complex: maximum increase from baseline \>=25% or \>=50%; 5) QT interval \>=500 msec; 6) QT interval corrected using Bazett's formula (QTcB): 450 to less than (\<) 480 msec, 7) QTcB: 480 to \<500 msec, 8) QTcB: \>=500 msec, 10) QTcB: 30 to \<60 msec increase from baseline, 11) QTcB: \>=60 msec increase from baseline; 9) QT interval corrected using the Fridericia's formula (QTcF): 450 to \<480 msec, 10) QTcF: 480 to \< 500 msec, 11) QTcF: \>=500 msec, 12) QTcF: 30 to \<60 msec increase from baseline, 13) QTcF: change\>=60 msec increase from baseline.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcB interval: 480 to < 500 msec	4 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcB interval >= 500 msec	0 Participants	3 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcF interval: >=60 msec increase	2 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities PR interval >=300 msec	0 Participants	0 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities PR interval: 25% or 50% increase	0 Participants	0 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QRS complex >=200 msec	0 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QRS interval: >=25% or 50% increase	1 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QT interval >=500 msec	2 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcB interval: 450 to < 480 msec	19 Participants	22 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcB interval: 30 to <60 msec increase	11 Participants	13 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcB interval: >=60 msec increase	0 Participants	1 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcF interval: 450 to <480 msec	9 Participants	12 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcF interval: 480 to <500 msec	4 Participants	0 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcF Interval >= 500 msec	0 Participants	3 Participants
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities QTcF interval: 30 to <60 msec increase	6 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening (28 days before Baseline), Week 12

The complete physical and neurological examination included examination of abdomen, ears, extremities, eyes, general, head, heart, lungs, lymph nodes, mouth, musculoskeletal, neck, nose, ocular fundi, pulse, skin, throat, thyroid, and others. Abnormality was judged by investigator.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Extremities: Screening	15 Participants	15 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations General: Screening	1 Participants	2 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations General: Week 12	2 Participants	2 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Head: Screening	1 Participants	1 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Head: Week 12	1 Participants	1 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Heart: Screening	3 Participants	8 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Heart: Week 12	3 Participants	5 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Lungs: Screening	3 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Abdomen: Screening	9 Participants	9 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Abdomen: Week 12	5 Participants	6 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Ears: Screening	6 Participants	9 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Ears: Week 12	3 Participants	9 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Extremities: Week 12	10 Participants	11 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Eyes: Screening	26 Participants	26 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Eyes: Week 12	24 Participants	22 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Lungs: Week 12	3 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Lymph nodes: Screening	0 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Lymph nodes: Week 12	0 Participants	1 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Mouth: Screening	11 Participants	3 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Mouth: Week 12	9 Participants	3 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Musculoskeletal: Screening	11 Participants	13 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Musculoskeletal: Week 12	7 Participants	12 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Neck: Screening	1 Participants	2 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Neck: Week 12	0 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Nose: Screening	0 Participants	2 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Nose: Week 12	0 Participants	1 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Ocular fundi: Screening	1 Participants	2 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Ocular fundi: Week 12	1 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Pulses: Screening	2 Participants	3 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Pulses: Week 12	0 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Skin: Screening	30 Participants	23 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Skin: Week 12	25 Participants	21 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Throat: Screening	0 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Throat: Week 12	0 Participants	0 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Thyroid: Screening	0 Participants	3 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Thyroid: Week 12	0 Participants	3 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Other: Screening	2 Participants	1 Participants
Number of Participants With Abnormal Physical Examinations and Neurological Examinations Other: Week 12	0 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, Baseline, Post-baseline (Week 1 up to 12)

C-SSRS assessed whether participant experienced the following: suicidal behavior which includes suicide attempt, interrupted attempt, aborted attempt, and preparatory acts towards imminent suicidal behavior (response of "Yes" on "preparatory acts or behavior"); suicidal ideation (response of "Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent); self-injurious behavior (SIB), intent unknown (response of "Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior?").

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal behavior: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicide attempt: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Interrupted attempt: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Aborted attempt: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Imminent suicidal behavior: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal ideation: Screening	5 Participants	6 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Non-suicidal SIB: Screening	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal behavior: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicide attempt: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Interrupted Attempt: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Aborted attempt: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Imminent suicidal behavior: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal ideation: Baseline	4 Participants	5 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Non-Suicidal SIB: Baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal behavior: Post baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicide attempt: Post baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Interrupted attempt: Post baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Aborted attempt: Post baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Imminent suicidal behavior:Post baseline	0 Participants	0 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal ideation: Post baseline	6 Participants	6 Participants
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) Non-suicidal SIB: Post baseline	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12

Population: FAS included all the participants who consumed at least 1 dose of randomized study medication. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this measure and "Number Analyzed" signifies those participants who were evaluable for this measure at the specified time points.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=80 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
PF-04447943 Plasma Concentration Week 1	NA nanogram per milliliter Data was not estimable as none of the participants had concentration above than lower limit of quantification.	71.60 nanogram per milliliter Interval 0.0 to 407.0
PF-04447943 Plasma Concentration Week 3	NA nanogram per milliliter Data was not estimable as none of the participants had concentration above than lower limit of quantification.	241.0 nanogram per milliliter Interval 0.0 to 561.0
PF-04447943 Plasma Concentration Week 6	NA nanogram per milliliter Data was not estimable as none of the participants had concentration above than lower limit of quantification.	225.0 nanogram per milliliter Interval 0.0 to 693.0
PF-04447943 Plasma Concentration Week 9	0.0000 nanogram per milliliter Interval 0.0 to 40.6	239.5 nanogram per milliliter Interval 0.0 to 738.0
PF-04447943 Plasma Concentration Week 12	NA nanogram per milliliter Data was not estimable as none of the participants had concentration above than lower limit of quantification.	250.5 nanogram per milliliter Interval 0.0 to 598.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension

Population: Safety analysis set included all participants who consumed at least 1 dose of the investigational or control drug. "Number Analyzed" signifies those participants who were evaluable for the specified rows for each arm, respectively.

Pre-defined criteria vital signs abnormalities included maximum increase or decrease of greater than or equal to (\>=) 30 millimeters of mercury (mmHg) from baseline for supine systolic blood pressure (SBP); maximum increase or decrease of \>=20 mmHg from baseline for supine diastolic BP (DBP); maximum increase or decrease of \>=30 mmHg from baseline for standing SBP; maximum increase or decrease of \>=20 mmHg from baseline for standing DBP. Orthostatic hypotension was defined as a drop of more than 10 mmHg in diastolic BP or a drop of more than 20 mmHg in systolic BP within 3 minutes of standing from the supine position.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 Participants PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Orthostatic Hypotension: Week 12	5 Participants	4 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Increase in supine SBP (>=30 mmHg)	9 Participants	4 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Decrease in supine SBP (>=30 mmHg)	5 Participants	8 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Increase in standing SBP (>=30 mmHg)	6 Participants	7 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Decrease in Standing SBP (>=30 mmHg)	11 Participants	9 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Increase in supine DBP (>=20 mmHg)	3 Participants	2 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Decrease in Supine DBP (>=20 mmHg) (	9 Participants	8 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Increase in standing DBP(>=20 mmHg)	4 Participants	3 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Decrease in Standing DBP(>=20 mmHg)	4 Participants	6 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Orthostatic Hypotension: Week 1	5 Participants	3 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Orthostatic Hypotension: Week 3	3 Participants	3 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Orthostatic Hypotension: Week 6	4 Participants	2 Participants
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities Orthostatic Hypotension: Week 9	2 Participants	4 Participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 56 other events

Deaths: 0 deaths

PF-04447943

Serious events: 3 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=100 participants at risk Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks.	PF-04447943 n=91 participants at risk PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks.
Cardiac disorders Cardiac arrest	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Chronic hepatic failure	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic cirrhosis	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Postoperative wound infection	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Ankle fracture	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Traumatic brain injury	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haematoma	0.00% 0/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.1% 1/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.0% 1/100 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/91 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

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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.
Publication restrictions are in place

Restriction type: OTHER