A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00930059
Collaborator
(none)
191
44
2
12.4
4.3
0.4
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effects of PF-04447943 compared to placebo on cognitive, behavioral and overall symptoms of Alzheimer's disease; evaluate the safety and tolerability of PF-0444793 compared to placebo; and determine the levels of PF-04447943 in the plasma over the course of the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
191 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A PHASE 2 MULTICENTER, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP STUDY OF PF-04447943 IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE
Actual Study Start Date
:
Sep 10, 2009
Actual Primary Completion Date
:
Sep 22, 2010
Actual Study Completion Date
:
Sep 22, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-04447943
|
Drug: PF-04447943
tablets, 25 mg every 12 hours for 12 wks
|
| Placebo Comparator: Placebo
|
Drug: Placebo
matching placebo tablets, every 12 hours for 12 wks
|
Outcome Measures
Primary Outcome Measures
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline [Baseline (Day 1)]
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.
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 12 [Baseline, Week 12]
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.
Secondary Outcome Measures
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 [Baseline, Week 3, 6, 9]
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.
- Clinical Global Impression - Improvement (CGI-I) [Week 3, 6, 9, 12]
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.
- Neuropsychiatric Inventory (NPI) Total Score at Baseline [Baseline]
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.
- Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 [Baseline, Week 3, 6, 9, 12]
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.
Other Outcome Measures
- Number of Participants With Laboratory Test Abnormalities [Baseline up to Week 12]
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.
- Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities [Baseline up to Week 12]
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.
- Number of Participants With Abnormal Physical Examinations and Neurological Examinations [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.
- Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [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?").
- PF-04447943 Plasma Concentration [Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12]
- Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities [Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Mild to moderate Alzheimer's disease (MMSE 14-26)
-
Good general health (such controlled conditions as Type 2 diabetes and hypertension allowed)
Exclusion Criteria:
-
Use of acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine within 12 weeks of the start of the study
-
Significant cardiovascular disease in the past 6 months
-
Illness other than Alzheimer's disease that could contribute to cognitive impairment
-
History of stroke or seizure disorder
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neurology Clinic, PC | Northport | Alabama | United States | 35476 |
| 2 | ATP Clinical Research, Inc. | Costa Mesa | California | United States | 92626 |
| 3 | Southwestern Research Incorporated | Glendale | California | United States | 91204 |
| 4 | Pacific Coast Imaging (for Imaging only) | Newport Beach | California | United States | 92663 |
| 5 | The Southwest Institute for Clinical Research, Inc. | Rancho Mirage | California | United States | 92270 |
| 6 | Pacific Research Network (Satellite Site) | San Diego | California | United States | 92128 |
| 7 | Pacific Research Network, Inc. (Satellite Site) | Vista | California | United States | 92081 |
| 8 | MD Clinical | Hallandale Beach | Florida | United States | 33009 |
| 9 | Compass Research, LLC | Orlando | Florida | United States | 32806 |
| 10 | Berma Research Group | Plantation | Florida | United States | 33317 |
| 11 | Joliet Center for Clinical Research | Joliet | Illinois | United States | 60435 |
| 12 | Fort Wayne Neurological Center | Fort Wayne | Indiana | United States | 46805 |
| 13 | Agewell | Indianapolis | Indiana | United States | 46260 |
| 14 | Four Rivers Clinical Research, Inc. | Paducah | Kentucky | United States | 42003 |
| 15 | Advanced MRI | Lake Charles | Louisiana | United States | 70601 |
| 16 | Lake Charles Clinical Trials, LLC | Lake Charles | Louisiana | United States | 70601 |
| 17 | Neurocare, Inc. | Newton | Massachusetts | United States | 02459 |
| 18 | Neurobehavioral Research Inc | Cedarhurst | New York | United States | 11516 |
| 19 | Behavioral Medical Research of Staten Island | Staten Island | New York | United States | 10305 |
| 20 | University of Pittsburgh Alzheimer's Disease Research Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 21 | Rhode Island Hospital, Alzheimer's Disease and Memory Disorders Center | Providence | Rhode Island | United States | 02903 |
| 22 | Neurology Clinic, PC | Cordova | Tennessee | United States | 38018 |
| 23 | Medical Arts Health Research Group | Kelowna | British Columbia | Canada | V1Y 3G8 |
| 24 | Hamilton Health Sciences | Hamilton | Ontario | Canada | L9C 7N4 |
| 25 | Kawartha Regional Memory Clinic | Peterborough | Ontario | Canada | K9H 2P4 |
| 26 | Neuro Rive Sud Clinic | Greenfield Park | Quebec | Canada | J4V 2J2 |
| 27 | Diex Recherche Inc. | Sherbrooke | Quebec | Canada | J1H 1Z1 |
| 28 | Psicomed Estudios Clinicos | Antofagasta | II Region | Chile | |
| 29 | Centro Doctora Lissette Duque | Providencia | RM | Chile | 7500617 |
| 30 | Psicomedica Research Group | Santiago | RM | Chile | 7500710 |
| 31 | Hospital Del Salvador | Santiago | RM | Chile | 7500922 |
| 32 | Neuroconsult | Santiago | RM | Chile | 7550112 |
| 33 | Especialidades Medicas L y S | Santiago | RM | Chile | 7560356 |
| 34 | Neuropsicologia Ltda. | La Florida | Santiago | Chile | 8260094 |
| 35 | Hospital Base Valdivia | Valdivia | XIV Region | Chile | 5090145 |
| 36 | Fakultni nemocnice | Hradec Kralove | Czechia | 500 05 | |
| 37 | Pardubicka krajska nemocnice, a.s. | Pardubice | Czechia | 53203 | |
| 38 | Pragtis, s.r.o. | Praha 2 | Czechia | 120 00 | |
| 39 | Fakultni nemocnice v Motole | Praha 5 | Czechia | 150 08 | |
| 40 | Psychiatry Trial, s.r.o. | Praha 5 | Czechia | 15800 | |
| 41 | Psychiatricka ambulance | Praha 8 | Czechia | 180 00 | |
| 42 | Neurologie - EEG, s.r.o | Praha 8 | Czechia | 18000 | |
| 43 | Centrum neurologicke pece, s.r.o. | Rychnov nad Kneznou | Czechia | 51601 | |
| 44 | Psychiatricka ambulance | Strakonice | Czechia | 386 01 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00930059
Other Study ID Numbers:
- B0401005
- 2009-012179-82
First Posted:
Jun 30, 2009
Last Update Posted:
Nov 19, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Period Title: Overall Study | ||
| STARTED | 100 | 91 |
| COMPLETED | 92 | 79 |
| NOT COMPLETED | 8 | 12 |
Baseline Characteristics
| Arm/Group Title | Placebo | PF-04447943 | Total |
|---|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. | Total of all reporting groups |
| Overall Participants | 100 | 91 | 191 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
73.5
(7.5)
|
73.6
(8.2)
|
73.5
(7.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
64
64%
|
58
63.7%
|
122
63.9%
|
| Male |
36
36%
|
33
36.3%
|
69
36.1%
|
Outcome Measures
| Title | Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who consumed at least 1 dose of randomized study medication. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Mean (Standard Deviation) [units on a scale] |
21.87
(10.42)
|
22.66
(10.39)
|
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 12 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 93 | 80 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.60
(0.50)
|
-1.91
(0.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Least squares (LS) mean difference and p-values were based on analysis of covariance (ANCOVA) on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3353 |
| Comments | The primary test of significance was 1-sided, and a nominal Type I error rate a = 0.05 was employed. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 90% -1.52 to 0.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 3, 6, 9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Change at Week 3 |
-1.36
(0.49)
|
-1.16
(0.52)
|
| Change at Week 6 |
-1.17
(0.50)
|
-1.53
(0.53)
|
| Change at Week 9 |
-2.05
(0.50)
|
-2.68
(0.53)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 3: LS mean difference and p-values were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6073 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.20 | |
| Confidence Interval |
(2-Sided) 90% -0.99 to 1.38 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 6: LS mean difference and p-values were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3086 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 90% -1.56 to 0.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 9: LS mean difference and p-values were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1970 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.62 | |
| Confidence Interval |
(2-Sided) 90% -1.82 to 0.58 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
| Title | Clinical Global Impression - Improvement (CGI-I) |
|---|---|
| Description | 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. |
| Time Frame | Week 3, 6, 9, 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Week 3 |
3.64
(0.10)
|
3.70
(0.10)
|
| Week 6 |
3.51
(0.10)
|
3.58
(0.11)
|
| Week 9 |
3.63
(0.10)
|
3.45
(0.11)
|
| Week 12 |
3.53
(0.10)
|
3.32
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Week 3: Inferential statistics were based on linear model with fixed effects for visit (nominal scale) and visit by treatment interaction, and a random effect for participant. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6547 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | Linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 90% -0.18 to 0.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Week 6: Inferential statistics were based on linear model with fixed effects for visit (nominal scale) and visit by treatment interaction, and a random effect for participant. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7020 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | Linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) 90% -0.16 to 0.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Week 9: Inferential statistics were based on linear model with fixed effects for visit (nominal scale) and visit by treatment interaction, and a random effect for participant. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1138 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | Linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 90% -0.41 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Week 12: Inferential statistics were based on linear model with fixed effects for visit (nominal scale) and visit by treatment interaction, and a random effect for participant. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0816 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | Linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.20 | |
| Confidence Interval |
(2-Sided) 90% -0.44 to 0.04 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
| Title | Neuropsychiatric Inventory (NPI) Total Score at Baseline |
|---|---|
| Description | 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. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who consumed at least 1 dose of randomized study medication. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Mean (Standard Deviation) [units on a scale] |
12.16
(12.86)
|
10.67
(11.28)
|
| Title | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 3, 6, 9, 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Change at Week 3 |
-2.02
(0.66)
|
-1.33
(0.70)
|
| Change at Week 6 |
-2.61
(0.66)
|
-1.76
(0.71)
|
| Change at Week 9 |
-3.44
(0.66)
|
-2.49
(0.72)
|
| Change at Week 12 |
-2.70
(0.67)
|
-2.86
(0.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 3: LS mean difference and p-value were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7634 |
| Comments | No adjustments have been made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) 90% -0.89 to 2.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 6: LS mean difference and p-value were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8077 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 90% -0.75 to 2.45 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 9: LS mean difference and p-value were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8350 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 90% -0.66 to 2.57 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.98 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-04447943 |
|---|---|---|
| Comments | Change at Week 12: LS mean difference and p-value were based on ANCOVA on change from baseline with treatment, baseline value, scheduled visit and visit by treatment interaction as covariates, and participant effect as random effect. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4377 |
| Comments | No adjustments made for multiple comparisons. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 90% -1.78 to 1.48 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.99 |
|
| Estimation Comments | ||
| Title | Number of Participants With Laboratory Test Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 99 | 88 |
| Count of Participants [Participants] |
33
33%
|
28
30.8%
|
| Title | Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| PR interval >=300 msec |
0
0%
|
0
0%
|
| PR interval: 25% or 50% increase |
0
0%
|
0
0%
|
| QRS complex >=200 msec |
0
0%
|
1
1.1%
|
| QRS interval: >=25% or 50% increase |
1
1%
|
1
1.1%
|
| QT interval >=500 msec |
2
2%
|
1
1.1%
|
| QTcB interval: 450 to < 480 msec |
19
19%
|
22
24.2%
|
| QTcB interval: 480 to < 500 msec |
4
4%
|
1
1.1%
|
| QTcB interval >= 500 msec |
0
0%
|
3
3.3%
|
| QTcB interval: 30 to <60 msec increase |
11
11%
|
13
14.3%
|
| QTcB interval: >=60 msec increase |
0
0%
|
1
1.1%
|
| QTcF interval: 450 to <480 msec |
9
9%
|
12
13.2%
|
| QTcF interval: 480 to <500 msec |
4
4%
|
0
0%
|
| QTcF Interval >= 500 msec |
0
0%
|
3
3.3%
|
| QTcF interval: 30 to <60 msec increase |
6
6%
|
10
11%
|
| QTcF interval: >=60 msec increase |
2
2%
|
1
1.1%
|
| Title | Number of Participants With Abnormal Physical Examinations and Neurological Examinations |
|---|---|
| Description | 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. |
| Time Frame | Screening (28 days before Baseline), Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Abdomen: Screening |
9
9%
|
9
9.9%
|
| Abdomen: Week 12 |
5
5%
|
6
6.6%
|
| Ears: Screening |
6
6%
|
9
9.9%
|
| Ears: Week 12 |
3
3%
|
9
9.9%
|
| Extremities: Screening |
15
15%
|
15
16.5%
|
| Extremities: Week 12 |
10
10%
|
11
12.1%
|
| Eyes: Screening |
26
26%
|
26
28.6%
|
| Eyes: Week 12 |
24
24%
|
22
24.2%
|
| General: Screening |
1
1%
|
2
2.2%
|
| General: Week 12 |
2
2%
|
2
2.2%
|
| Head: Screening |
1
1%
|
1
1.1%
|
| Head: Week 12 |
1
1%
|
1
1.1%
|
| Heart: Screening |
3
3%
|
8
8.8%
|
| Heart: Week 12 |
3
3%
|
5
5.5%
|
| Lungs: Screening |
3
3%
|
0
0%
|
| Lungs: Week 12 |
3
3%
|
0
0%
|
| Lymph nodes: Screening |
0
0%
|
0
0%
|
| Lymph nodes: Week 12 |
0
0%
|
1
1.1%
|
| Mouth: Screening |
11
11%
|
3
3.3%
|
| Mouth: Week 12 |
9
9%
|
3
3.3%
|
| Musculoskeletal: Screening |
11
11%
|
13
14.3%
|
| Musculoskeletal: Week 12 |
7
7%
|
12
13.2%
|
| Neck: Screening |
1
1%
|
2
2.2%
|
| Neck: Week 12 |
0
0%
|
0
0%
|
| Nose: Screening |
0
0%
|
2
2.2%
|
| Nose: Week 12 |
0
0%
|
1
1.1%
|
| Ocular fundi: Screening |
1
1%
|
2
2.2%
|
| Ocular fundi: Week 12 |
1
1%
|
0
0%
|
| Pulses: Screening |
2
2%
|
3
3.3%
|
| Pulses: Week 12 |
0
0%
|
0
0%
|
| Skin: Screening |
30
30%
|
23
25.3%
|
| Skin: Week 12 |
25
25%
|
21
23.1%
|
| Throat: Screening |
0
0%
|
0
0%
|
| Throat: Week 12 |
0
0%
|
0
0%
|
| Thyroid: Screening |
0
0%
|
3
3.3%
|
| Thyroid: Week 12 |
0
0%
|
3
3.3%
|
| Other: Screening |
2
2%
|
1
1.1%
|
| Other: Week 12 |
0
0%
|
3
3.3%
|
| Title | Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) |
|---|---|
| Description | 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?"). |
| Time Frame | Screening, Baseline, Post-baseline (Week 1 up to 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Suicidal behavior: Screening |
0
0%
|
0
0%
|
| Suicide attempt: Screening |
0
0%
|
0
0%
|
| Interrupted attempt: Screening |
0
0%
|
0
0%
|
| Aborted attempt: Screening |
0
0%
|
0
0%
|
| Imminent suicidal behavior: Screening |
0
0%
|
0
0%
|
| Suicidal ideation: Screening |
5
5%
|
6
6.6%
|
| Non-suicidal SIB: Screening |
0
0%
|
0
0%
|
| Suicidal behavior: Baseline |
0
0%
|
0
0%
|
| Suicide attempt: Baseline |
0
0%
|
0
0%
|
| Interrupted Attempt: Baseline |
0
0%
|
0
0%
|
| Aborted attempt: Baseline |
0
0%
|
0
0%
|
| Imminent suicidal behavior: Baseline |
0
0%
|
0
0%
|
| Suicidal ideation: Baseline |
4
4%
|
5
5.5%
|
| Non-Suicidal SIB: Baseline |
0
0%
|
0
0%
|
| Suicidal behavior: Post baseline |
0
0%
|
0
0%
|
| Suicide attempt: Post baseline |
0
0%
|
0
0%
|
| Interrupted attempt: Post baseline |
0
0%
|
0
0%
|
| Aborted attempt: Post baseline |
0
0%
|
0
0%
|
| Imminent suicidal behavior:Post baseline |
0
0%
|
0
0%
|
| Suicidal ideation: Post baseline |
6
6%
|
6
6.6%
|
| Non-suicidal SIB: Post baseline |
0
0%
|
1
1.1%
|
| Title | PF-04447943 Plasma Concentration |
|---|---|
| Description | |
| Time Frame | Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 90 | 80 |
| Week 1 |
NA
|
71.60
|
| Week 3 |
NA
|
241.0
|
| Week 6 |
NA
|
225.0
|
| Week 9 |
0.0000
|
239.5
|
| Week 12 |
NA
|
250.5
|
| Title | Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Placebo | PF-04447943 |
|---|---|---|
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. |
| Measure Participants | 100 | 91 |
| Increase in supine SBP (>=30 mmHg) |
9
9%
|
4
4.4%
|
| Decrease in supine SBP (>=30 mmHg) |
5
5%
|
8
8.8%
|
| Increase in standing SBP (>=30 mmHg) |
6
6%
|
7
7.7%
|
| Decrease in Standing SBP (>=30 mmHg) |
11
11%
|
9
9.9%
|
| Increase in supine DBP (>=20 mmHg) |
3
3%
|
2
2.2%
|
| Decrease in Supine DBP (>=20 mmHg) ( |
9
9%
|
8
8.8%
|
| Increase in standing DBP(>=20 mmHg) |
4
4%
|
3
3.3%
|
| Decrease in Standing DBP(>=20 mmHg) |
4
4%
|
6
6.6%
|
| Orthostatic Hypotension: Week 1 |
5
5%
|
3
3.3%
|
| Orthostatic Hypotension: Week 3 |
3
3%
|
3
3.3%
|
| Orthostatic Hypotension: Week 6 |
4
4%
|
2
2.2%
|
| Orthostatic Hypotension: Week 9 |
2
2%
|
4
4.4%
|
| Orthostatic Hypotension: Week 12 |
5
5%
|
4
4.4%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||
| Arm/Group Title | Placebo | PF-04447943 | ||
| Arm/Group Description | Placebo matched to PF-04447943 tablet orally twice daily for 12 weeks. | PF-04447943 25 milligram (mg) tablet orally twice daily for 12 weeks. | ||
All Cause Mortality |
||||
| Placebo | PF-04447943 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | PF-04447943 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/100 (4%) | 3/91 (3.3%) | ||
| Cardiac disorders | ||||
| Cardiac arrest | 1/100 (1%) | 0/91 (0%) | ||
| Gastrointestinal disorders | ||||
| Intestinal obstruction | 0/100 (0%) | 1/91 (1.1%) | ||
| Hepatobiliary disorders | ||||
| Chronic hepatic failure | 1/100 (1%) | 0/91 (0%) | ||
| Hepatic cirrhosis | 1/100 (1%) | 0/91 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/100 (1%) | 0/91 (0%) | ||
| Postoperative wound infection | 1/100 (1%) | 0/91 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 1/100 (1%) | 0/91 (0%) | ||
| Fall | 1/100 (1%) | 1/91 (1.1%) | ||
| Hip fracture | 0/100 (0%) | 1/91 (1.1%) | ||
| Traumatic brain injury | 1/100 (1%) | 0/91 (0%) | ||
| Nervous system disorders | ||||
| Cerebral haematoma | 0/100 (0%) | 1/91 (1.1%) | ||
| Syncope | 1/100 (1%) | 0/91 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory arrest | 1/100 (1%) | 0/91 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | PF-04447943 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 56/100 (56%) | 57/91 (62.6%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenopathy | 1/100 (1%) | 0/91 (0%) | ||
| Thrombocytosis | 1/100 (1%) | 0/91 (0%) | ||
| Cardiac disorders | ||||
| Atrioventricular block first degree | 1/100 (1%) | 0/91 (0%) | ||
| Bundle branch block right | 0/100 (0%) | 1/91 (1.1%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 0/100 (0%) | 1/91 (1.1%) | ||
| Vertigo | 4/100 (4%) | 2/91 (2.2%) | ||
| Eye disorders | ||||
| Conjunctivitis | 1/100 (1%) | 0/91 (0%) | ||
| Eyelid irritation | 1/100 (1%) | 0/91 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/100 (2%) | 4/91 (4.4%) | ||
| Abdominal pain lower | 1/100 (1%) | 0/91 (0%) | ||
| Constipation | 1/100 (1%) | 1/91 (1.1%) | ||
| Diarrhoea | 3/100 (3%) | 5/91 (5.5%) | ||
| Dry mouth | 0/100 (0%) | 1/91 (1.1%) | ||
| Dyspepsia | 0/100 (0%) | 1/91 (1.1%) | ||
| Gastrooesophageal reflux disease | 0/100 (0%) | 1/91 (1.1%) | ||
| Nausea | 1/100 (1%) | 5/91 (5.5%) | ||
| Upper gastrointestinal haemorrhage | 0/100 (0%) | 1/91 (1.1%) | ||
| General disorders | ||||
| Asthenia | 2/100 (2%) | 0/91 (0%) | ||
| Chest pain | 0/100 (0%) | 2/91 (2.2%) | ||
| Fatigue | 1/100 (1%) | 1/91 (1.1%) | ||
| Irritability | 2/100 (2%) | 0/91 (0%) | ||
| Oedema peripheral | 2/100 (2%) | 1/91 (1.1%) | ||
| Immune system disorders | ||||
| Seasonal allergy | 1/100 (1%) | 0/91 (0%) | ||
| Infections and infestations | ||||
| Asymptomatic bacteriuria | 1/100 (1%) | 0/91 (0%) | ||
| Bacteriuria | 1/100 (1%) | 1/91 (1.1%) | ||
| Bronchitis | 2/100 (2%) | 3/91 (3.3%) | ||
| Cellulitis | 0/100 (0%) | 1/91 (1.1%) | ||
| Herpes zoster | 0/100 (0%) | 1/91 (1.1%) | ||
| Infection | 0/100 (0%) | 1/91 (1.1%) | ||
| Influenza | 2/100 (2%) | 3/91 (3.3%) | ||
| Labyrinthitis | 0/100 (0%) | 1/91 (1.1%) | ||
| Nasopharyngitis | 5/100 (5%) | 4/91 (4.4%) | ||
| Upper respiratory tract infection | 1/100 (1%) | 0/91 (0%) | ||
| Urinary tract infection | 1/100 (1%) | 0/91 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 1/100 (1%) | 1/91 (1.1%) | ||
| Joint sprain | 1/100 (1%) | 2/91 (2.2%) | ||
| Skin laceration | 1/100 (1%) | 1/91 (1.1%) | ||
| Stab wound | 1/100 (1%) | 0/91 (0%) | ||
| Wound | 1/100 (1%) | 0/91 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/100 (1%) | 0/91 (0%) | ||
| Aspartate aminotransferase increased | 1/100 (1%) | 0/91 (0%) | ||
| Blood alkaline phosphatase increased | 0/100 (0%) | 1/91 (1.1%) | ||
| Blood creatinine increased | 0/100 (0%) | 1/91 (1.1%) | ||
| Blood glucose increased | 2/100 (2%) | 3/91 (3.3%) | ||
| Blood pressure decreased | 0/100 (0%) | 1/91 (1.1%) | ||
| Blood pressure increased | 0/100 (0%) | 1/91 (1.1%) | ||
| Blood sodium increased | 0/100 (0%) | 1/91 (1.1%) | ||
| Carotid bruit | 0/100 (0%) | 1/91 (1.1%) | ||
| Liver function test abnormal | 1/100 (1%) | 0/91 (0%) | ||
| Transaminases increased | 1/100 (1%) | 0/91 (0%) | ||
| White blood cell count increased | 0/100 (0%) | 1/91 (1.1%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 0/100 (0%) | 1/91 (1.1%) | ||
| Glucose tolerance impaired | 0/100 (0%) | 1/91 (1.1%) | ||
| Hyperglycaemia | 2/100 (2%) | 2/91 (2.2%) | ||
| Hypokalaemia | 1/100 (1%) | 0/91 (0%) | ||
| Hyponatraemia | 1/100 (1%) | 0/91 (0%) | ||
| Increased appetite | 1/100 (1%) | 0/91 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/100 (1%) | 0/91 (0%) | ||
| Back pain | 1/100 (1%) | 0/91 (0%) | ||
| Joint swelling | 1/100 (1%) | 0/91 (0%) | ||
| Muscle spasms | 1/100 (1%) | 0/91 (0%) | ||
| Spinal osteoarthritis | 0/100 (0%) | 1/91 (1.1%) | ||
| Right Knee Sore | 1/100 (1%) | 0/91 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Seborrhoeic keratosis | 1/100 (1%) | 0/91 (0%) | ||
| Thyroid neoplasm | 1/100 (1%) | 0/91 (0%) | ||
| Dizziness | 2/100 (2%) | 4/91 (4.4%) | ||
| Neuralgia | 0/100 (0%) | 1/91 (1.1%) | ||
| Nervous system disorders | ||||
| Headache | 7/100 (7%) | 7/91 (7.7%) | ||
| Poor quality sleep | 0/100 (0%) | 1/91 (1.1%) | ||
| Sedation | 1/100 (1%) | 0/91 (0%) | ||
| Somnolence | 2/100 (2%) | 3/91 (3.3%) | ||
| Tension headache | 2/100 (2%) | 0/91 (0%) | ||
| Psychiatric disorders | ||||
| Abnormal behaviour | 1/100 (1%) | 1/91 (1.1%) | ||
| Aggression | 0/100 (0%) | 1/91 (1.1%) | ||
| Agitation | 0/100 (0%) | 1/91 (1.1%) | ||
| Anxiety | 2/100 (2%) | 1/91 (1.1%) | ||
| Confusional state | 1/100 (1%) | 1/91 (1.1%) | ||
| Depressed mood | 1/100 (1%) | 0/91 (0%) | ||
| Depression | 1/100 (1%) | 1/91 (1.1%) | ||
| Eating disorder | 0/100 (0%) | 1/91 (1.1%) | ||
| Initial insomnia | 1/100 (1%) | 0/91 (0%) | ||
| Insomnia | 3/100 (3%) | 4/91 (4.4%) | ||
| Nightmare | 0/100 (0%) | 1/91 (1.1%) | ||
| Restlessness | 1/100 (1%) | 1/91 (1.1%) | ||
| Suicidal ideation | 1/100 (1%) | 0/91 (0%) | ||
| Renal and urinary disorders | ||||
| Glycosuria | 0/100 (0%) | 1/91 (1.1%) | ||
| Haematuria | 1/100 (1%) | 0/91 (0%) | ||
| Pyuria | 1/100 (1%) | 0/91 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/100 (1%) | 1/91 (1.1%) | ||
| Dyspnoea | 2/100 (2%) | 0/91 (0%) | ||
| Hiccups | 0/100 (0%) | 1/91 (1.1%) | ||
| Productive cough | 0/100 (0%) | 1/91 (1.1%) | ||
| Sputum discoloured | 0/100 (0%) | 1/91 (1.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis | 0/100 (0%) | 1/91 (1.1%) | ||
| Dermatitis contact | 1/100 (1%) | 0/91 (0%) | ||
| Ecchymosis | 0/100 (0%) | 1/91 (1.1%) | ||
| Hyperhidrosis | 2/100 (2%) | 2/91 (2.2%) | ||
| Night sweats | 1/100 (1%) | 0/91 (0%) | ||
| Pruritus | 1/100 (1%) | 0/91 (0%) | ||
| Rash | 0/100 (0%) | 1/91 (1.1%) | ||
| Rosacea | 0/100 (0%) | 1/91 (1.1%) | ||
| Skin lesion | 0/100 (0%) | 2/91 (2.2%) | ||
| Vascular disorders | ||||
| Hypertension | 1/100 (1%) | 1/91 (1.1%) | ||
| Orthostatic hypotension | 1/100 (1%) | 1/91 (1.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00930059
Other Study ID Numbers:
- B0401005
- 2009-012179-82
First Posted:
Jun 30, 2009
Last Update Posted:
Nov 19, 2020
Last Verified:
Oct 1, 2020