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Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil

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ClinicalTrials.gov Identifier: NCT01712074
Recruitment Status : Terminated (The study was terminated October 23, 2015 as pre-specified, interim analysis futility criteria were met. The termination was not due to safety concerns.)
First Posted : October 23, 2012
Results First Posted : March 20, 2017
Last Update Posted : March 20, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: PF-05212377 (SAM-760)
Other: Placebo
Enrollment 186
Recruitment Details Before entering in the 12-week treatment period, participants were required to enter a 4-week placebo run-in period. 195 participants started the placebo run-in period, of which 186 were eligible for the treatment period. Among the 186 enrolled participants, 185 were treated with the double-blind study treatment, 1 was enrolled but not treated.
Pre-assignment Details This study was a multicenter Phase 2a, randomized, placebo controlled, safety and efficacy study of 18 weeks in duration in participants with mild-to-moderate Alzheimer’s disease (AD) who were stable on treatment with 5 or 10 mg of donepezil and who had existing neuropsychiatric symptoms.
Arm/Group Title Placebo Run-In PF-05212377 30 mg: Double Blind Period Placebo: Double Blind Period
Hide Arm/Group Description Participants that received placebo during the 4-week single blind placebo run-in period All participants that received PF-05212377 30 mg during the 12-week double blind period All participants that received placebo during the 12-week double blind period
Period Title: Placebo Run-in Period
Started 195 0 0
Completed 185 0 0
Not Completed 10 0 0
Reason Not Completed
Adverse Event             2             0             0
Lost to Follow-up             1             0             0
No longer meets eligibility criteria             5             0             0
Other             1             0             0
No longer willing to participate             1             0             0
Period Title: Double Blind Period
Started 0 91 94
Completed 0 77 86
Not Completed 0 14 8
Reason Not Completed
Adverse Event             0             2             1
No longer willing to participate             0             2             4
Death             0             1             0
Lost to Follow-up             0             2             1
Other             0             4             1
Protocol Violation             0             0             1
No longer met eligibility criteria             0             3             0
Arm/Group Title Not Randomized PF-05212377 30 mg: Double Blind Period Placebo: Double Blind Period Total
Hide Arm/Group Description Participants who have been discontinued during the Placebo Run-In period All participants entered the double blind period and received PF-05212377 30 mg All participants entered the double blind period and received placebo Total of all reporting groups
Overall Number of Baseline Participants 9 92 94 195
Hide Baseline Analysis Population Description
One (1) of participant randomized but not treated appeared under placebo run-in including his/her discontinued and safety information
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 92 participants 94 participants 195 participants
73.2  (8.8) 76.0  (8.0) 75.9  (7.5) 76  (7.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 92 participants 94 participants 195 participants
FEMALE
7
  77.8%
46
  50.0%
55
  58.5%
108
  55.4%
MALE
2
  22.2%
46
  50.0%
39
  41.5%
87
  44.6%
1.Primary Outcome
Title Change From Baseline in ADAS-cog13 Total Score at Week 16
Hide Description ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) is defined as all participants who were randomized. The FAS was the primary analysis set for efficacy data.
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants who received placebo contributing to the analysis during the double blind period
Overall Number of Participants Analyzed 78 86
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
0.111  (0.6290) -0.584  (0.5995)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05212377 30 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4256
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.695
Confidence Interval (2-Sided) 80%
-0.424 to 1.814
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.8697
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5)
Hide Description The NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. The NPI total score (for 12 behavioral domains) is calculated as the product of frequency and severity for each domain, and ranges from 0 to 144. An increase in score indicates a worsening of symptoms.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is defined as all participants who are randomized. The FAS was the primary analysis set for efficacy data.
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants who received placebo contributing to the analysis during the double blind period
Overall Number of Participants Analyzed 78 87
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-3.990  (1.2441) -6.184  (1.1801)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05212377 30 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2027
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.194
Confidence Interval (2-Sided) 80%
-0.013 to 4.401
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.7149
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation
Hide Description Proportion of participants with TEAEs leading to discontinuation over the 12-week double blind treatment period and washout. Adverse events (AEs) occurring following start of treatment or increasing in severity were counted as treatment emergent
Time Frame Week 4 to Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during double blind period
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo during double blind period
Overall Number of Participants Analyzed 91 94
Measure Type: Number
Unit of Measure: Percentage of Participants
3.3 0
4.Other Pre-specified Outcome
Title Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period
Hide Description

Proportion (%) of participants with laboratory abnormalities (without regard to baseline abnormalities) of potential clinical concern over the 12-week double blind treatment period.

The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (only at screening or needed: urine drug screen, thyroid panel, Vitamin B12, methylmalonic acid, folate and Hemoglobin A1).

Time Frame Week 4 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing clinical laboratory data during double blind period
Overall Number of Participants Analyzed 91 94
Measure Type: Number
Unit of Measure: Percentage of Participants
36.0 52.0
5.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3)
Hide Description The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants who received placebo with non-missing ECG data during the double blind period
Overall Number of Participants Analyzed 85 89
Mean (Full Range)
Unit of Measure: milliseconds (msec)
-2.8
(-52 to 24)
-3.6
(-82 to 35)
6.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4)
Hide Description The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
Time Frame Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 79 87
Mean (Full Range)
Unit of Measure: msec
-0.1
(-42 to 23)
-1.3
(-61 to 61)
7.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5)
Hide Description The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
Time Frame Baseline and Week 16/Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 82 85
Mean (Full Range)
Unit of Measure: msec
-2.5
(-69 to 24)
-1.6
(-49 to 33)
8.Other Pre-specified Outcome
Title Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern
Hide Description Proportion (%) of participants with PR Interval abnormalities meeting categorical criteria over the 12 week double blind treatment period. The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline PR absolute value>=300 msec , a PR increase of >=25% (for participants with a baseline value>=200 msec), or with an increase >=50% (for participants with a baseline value<200 msec) were counted.
Time Frame Week 4 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 86 90
Measure Type: Number
Unit of Measure: Percentage of Participants
Post-Baseline Maximum Absolute Value >=300 msec 0 4.4
Post-Baseline Maximum Increase >=25/50% 0 0
9.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3)
Hide Description The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 88 92
Mean (Full Range)
Unit of Measure: msec
-0.3
(-22 to 43)
-0.8
(-14 to 10)
10.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4)
Hide Description The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
Time Frame Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 81 90
Mean (Full Range)
Unit of Measure: msec
-0.1
(-13 to 45)
0.1
(-15 to 22)
11.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5)
Hide Description The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
Time Frame Baseline and Week 16/Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 85 89
Mean (Full Range)
Unit of Measure: msec
0.1
(-14 to 18)
-0.3
(-21 to 14)
12.Other Pre-specified Outcome
Title Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern
Hide Description Proportion (%) of participants with QRS Complex abnormalities meeting categorical criteria over the 12 week double blind treatment period. The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline QRS complex absolute value>=100 msec , a QRS complex increase of >=25% (for participants with a baseline value>=100 msec), or with an increase >=50% (for participants with a baseline value<100 msec) were counted.
Time Frame Week 4 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 91 93
Measure Type: Number
Unit of Measure: Percentage of participants
Post-Baseline Maximum Absolute Value >=200 msec 0 0
Post-Baseline Maximum Increase >=25/50% 0 0
13.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3)
Hide Description The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 88 92
Mean (Full Range)
Unit of Measure: msec
-3.0
(-31 to 37)
-4.9
(-35 to 35)
14.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4)
Hide Description The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
Time Frame Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 81 90
Mean (Full Range)
Unit of Measure: msec
-0.2
(-38 to 47)
-5.5
(-40 to 48)
15.Other Pre-specified Outcome
Title Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5)
Hide Description The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
Time Frame Baseline and Week 16/Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 85 89
Mean (Full Range)
Unit of Measure: msec
0.8
(-31 to 34)
-2.2
(-62 to 30)
16.Other Pre-specified Outcome
Title Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern
Hide Description

Proportion (%) of participants with QTcF Interval abnormalities meeting categorical criteria over the 12-week double blind treatment period. The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.

Participants with a post-baseline QTcF absolute value of 450 - <480, 480 - <500, or >=500 mec, or with a post-baseline QTcF increase of 30 - <60 or >=60 msec were counted.

Time Frame Week 4 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing ECG data during double blind period
Overall Number of Participants Analyzed 91 93
Measure Type: Number
Unit of Measure: Percentage of Participants
Post-Baseline Absolute Value of 450-<480 msec 15.4 14.0
Post-Baseline Absolute Value of 480-<500 msec 4.4 1.1
Change from Baseline of 30 -<60 msec 6.6 3.2
Change from Baseline >=60 msec 0 0
17.Other Pre-specified Outcome
Title Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3)
Hide Description The BP changes from baseline at Week 6 (Visit 3) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 89 93
Mean (Full Range)
Unit of Measure: millimeters of mercury (mm Hg)
Supine Systolic BP
-3.6
(-38 to 19)
-3.9
(-52 to 30)
Standing Systolic BP
-4.1
(-49 to 20)
-3.0
(-38 to 22)
Supine Diastolic BP
-2.2
(-37 to 26)
-1.8
(-33 to 20)
Standing Diastolic BP
-1.1
(-23 to 17)
-1.0
(-23 to 21)
18.Other Pre-specified Outcome
Title Pulse Rate Changes From Baseline - Week 6 (Visit 3)
Hide Description The pulse rate changes from baseline at Week 6 (Visit 3) including supine pulse rate, and standing pulse rate.
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 89 93
Mean (Full Range)
Unit of Measure: beats per minute (bpm)
Supine Pulse Rate
-1.4
(-30 to 30)
1.4
(-21 to 20)
Standing Pulse Rate
-0.3
(-20 to 30)
1.3
(-12 to 27)
19.Other Pre-specified Outcome
Title BP Changes From Baseline - Week 10 (Visit 4)
Hide Description The BP changes from baseline at Week 10 (Visit 4) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
Time Frame Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 81 91
Mean (Full Range)
Unit of Measure: mmHg
Supine Systolic BP
-3.4
(-36 to 20)
-0.3
(-68 to 34)
Standing Systolic BP
-3.8
(-33 to 32)
0.8
(-49 to 49)
Supine Diastolic BP
-2.4
(-32 to 20)
-0.7
(-39 to 25)
Standing Diastolic BP
-1.2
(-20 to 20)
0.3
(-26 to 39)
20.Other Pre-specified Outcome
Title Pulse Rate Changes From Baseline - Week 10 (Visit 4)
Hide Description The pulse rate changes from baseline at Week 10 (Visit 4) including supine pulse rate, and standing pulse rate.
Time Frame Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 81 91
Mean (Full Range)
Unit of Measure: bpm
Supine Pulse Rate
-0.4
(-26 to 22)
0.5
(-24 to 17)
Standing Pulse Rate
-0.7
(-20 to 24)
1.8
(-19 to 21)
21.Other Pre-specified Outcome
Title BP Changes From Baseline - Week 16/Early Termination (Visit 5)
Hide Description The BP changes from baseline at Week 16/Early Termination (Visit 5) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
Time Frame Baseline and Week 16/Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 85 90
Mean (Full Range)
Unit of Measure: mmHg
Supine Systolic BP
-1.4
(-30 to 27)
-1.1
(-30 to 72)
Standing Systolic BP
-1.0
(-30 to 32)
-1.1
(-26 to 66)
Supine Diastolic BP
-2.1
(-39 to 22)
-0.3
(-18 to 35)
Standing Diastolic BP
-0.8
(-23 to 23)
0.0
(-20 to 36)
22.Other Pre-specified Outcome
Title Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5)
Hide Description The pulse rate changes from baseline at Week 16/Early Termination (Visit 5) including supine pulse rate, and standing pulse rate.
Time Frame Baseline and Week 16/Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo with non-missing vital signs data during double blind period
Overall Number of Participants Analyzed 85 90
Mean (Full Range)
Unit of Measure: bpm
Supine Pulse Rate
-0.8
(-29 to 31)
0.6
(-22 to 20)
Standing Pulse Rate
-1.9
(-24 to 29)
0.8
(-17 to 17)
23.Other Pre-specified Outcome
Title Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern
Hide Description Proportion (%) of participants with vital signs abnormalities (absolute and change from baseline) meeting categorical criteria over the 12-week double blind treatment period were counted. Vital signs data included blood pressure (BP) and pulse rate.
Time Frame Week 4 to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any treatment during Week 4 (Visit 2) to Week 16 (Visit 5)
Arm/Group Title PF-05212377 30 mg Placebo
Hide Arm/Group Description:
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants receiving placebo during double blind period
Overall Number of Participants Analyzed 91 94
Measure Type: Number
Unit of Measure: Percentage of Participants
Absolute Supine Systolic BP<90 mmHg 0 1.1
Absolute Standing Systolic BP<90 mmHg 0 1.1
Absolute Supine Diastolic BP<50 mmHg 0 2.1
Absolute Standing Diastolic BP <50 mmHg 0 0
Absolute Supine Pulse Rate <40 bpm 0 0
Absolute Supine Pulse Rate >120 bpm 0 0
Absolute Standing Pulse Rate <40 bpm 0 0
Absolute Standing Pulse Rate >140 bpm 0 0
Increase in Supine Systolic BP>=30 mmHg 0 5.3
Increase in Standing Systolic BP>=30 mmHg 2.2 3.2
Increase in Supine Diastolic BP >=20 mmHg 4.4 4.3
Increase in Standing Diastolic BP >=20 mmHg 3.3 5.3
Decrease in Supine Systolic BP>=30 mmHg 5.5 5.3
Decrease in Standing Systolic BP>=30 mmHg 5.5 5.3
Decrease in Supine Diastolic BP >=20 mmHg 8.8 5.3
Decrease in Standing Diastolic BP >=20 mmHg 4.4 6.4
24.Other Pre-specified Outcome
Title Participants in Each Category of C-CASA Mapped From the C-SSRS Responses
Hide Description

Participants in each category of the Columbia Classification Algorithm of Suicide Assessment (C-CASA) mapped from the Columbia-Suicide Severity Rating Scale (C-SSRS) responses were reported.

C-CASA Event Code: <1> Completed suicide; <2> Suicide attempt; <3> Preparatory acts towards imminent suicidal behavior; <4> Suicidal Ideation; <7> Self-injurious behavior, no suicidal intent.

The suicidality assessments were performed at Screening, Week 0 (Visit 1), Week 4 (Visit 2), Week 6, (Visit 3), Week 10 (Visit 4), Week 16 (Visit 5), and Week 18 (Visit 6).

Only participants falling any category of C-CASA events were listed below.

Time Frame From Screening to Week 18/Early Termination
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All participants screened and assigned
Arm/Group Title Placebo Run-in PF-05212377 30 mg Placebo
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All participants assigned to the placebo run-in period
participants who received PF-05212377 30 mg contributing to the analysis during double blind period
All participants received placebo during double blind period
Overall Number of Participants Analyzed 195 91 94
Measure Type: Number
Unit of Measure: Participants
Week 4 (Visit 2): <4> 1 2 1
Week 6 (Visit 3): <4> 0 0 1
Week 10 (Visit 4): : <4> 0 2 0
Week 16/Early Termination (Visit 5): <4> 0 1 0
Week 4 (Visit 2): <7> 0 0 1
Week 6 (Visit 3): <7> 0 1 0
Time Frame Baseline through Week 18 (Visit 16)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Run-In PF-05212377 30 mg Placebo
Hide Arm/Group Description Participants received placebo during the single blind placebo run-in period participants who received PF-05212377 30 mg contributing to the analysis during double blind period All participants receiving placebo during double blind period
All-Cause Mortality
Placebo Run-In PF-05212377 30 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Run-In PF-05212377 30 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/195 (0.51%)      5/91 (5.49%)      3/94 (3.19%)    
Cardiac disorders       
Bradycardia * 1  0/195 (0.00%)  0 2/91 (2.20%)  2 0/94 (0.00%)  0
General disorders       
Accidental death * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 0/94 (0.00%)  0
Asthenia * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 0/94 (0.00%)  0
Hepatobiliary disorders       
Cholecystitis acute * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 0/94 (0.00%)  0
Infections and infestations       
Pneumonia * 1  0/195 (0.00%)  0 0/91 (0.00%)  0 1/94 (1.06%)  1
Urinary tract infection * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 0/94 (0.00%)  0
Injury, poisoning and procedural complications       
Femoral neck fracture * 1  1/195 (0.51%)  1 0/91 (0.00%)  0 0/94 (0.00%)  0
Foreign body * 1  0/195 (0.00%)  0 0/91 (0.00%)  0 1/94 (1.06%)  1
Psychiatric disorders       
Delirium * 1  0/195 (0.00%)  0 0/91 (0.00%)  0 1/94 (1.06%)  1
Vascular disorders       
Orthostatic hypotension * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 0/94 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Run-In PF-05212377 30 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/195 (6.67%)      25/91 (27.47%)      20/94 (21.28%)    
Gastrointestinal disorders       
Diarrhoea * 1  6/195 (3.08%)  6 8/91 (8.79%)  9 3/94 (3.19%)  3
General disorders       
Fatigue * 1  0/195 (0.00%)  0 2/91 (2.20%)  2 2/94 (2.13%)  2
Infections and infestations       
Urinary tract infection * 1  0/195 (0.00%)  0 5/91 (5.49%)  5 4/94 (4.26%)  4
Bronchitis * 1  0/195 (0.00%)  0 2/91 (2.20%)  2 1/94 (1.06%)  1
Nasopharyngitis * 1  4/195 (2.05%)  4 2/91 (2.20%)  2 2/94 (2.13%)  2
Pneumonia * 1  0/195 (0.00%)  0 0/91 (0.00%)  0 2/94 (2.13%)  2
Upper respiratory tract infection * 1  0/195 (0.00%)  0 2/91 (2.20%)  2 1/94 (1.06%)  1
Injury, poisoning and procedural complications       
Fall * 1  2/195 (1.03%)  2 3/91 (3.30%)  3 3/94 (3.19%)  3
Investigations       
Weight decreased * 1  1/195 (0.51%)  1 0/91 (0.00%)  0 2/94 (2.13%)  2
Nervous system disorders       
Headache * 1  0/195 (0.00%)  0 2/91 (2.20%)  2 1/94 (1.06%)  1
Psychiatric disorders       
Hallucination * 1  0/195 (0.00%)  0 0/91 (0.00%)  0 2/94 (2.13%)  2
Insomnia * 1  0/195 (0.00%)  0 1/91 (1.10%)  1 2/94 (2.13%)  3
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
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Name/Title: Pfizer
Organization: Pfizer
Phone: 1-8007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01712074     History of Changes
Other Study ID Numbers: B2081011
2014-000830-42 ( EudraCT Number )
First Submitted: October 19, 2012
First Posted: October 23, 2012
Results First Submitted: August 26, 2016
Results First Posted: March 20, 2017
Last Update Posted: March 20, 2017