Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, and Blood Levels of PF-03654746 in Subjects With Mild to Moderate Alzheimer's Disease (NCT NCT01028911)
NCT ID: NCT01028911
Last Updated: 2014-06-04
Results Overview
Criteria for potential clinical concern in vital signs: supine and standing systolic blood pressure (SBP) less than (\<) 90 millimeter of mercury (mmHg), supine and standing diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm, standing pulse rate \<40 bpm or \>140 bpm. Maximum increase or decrease from baseline in supine (Su) and standing (St) SBP \>=30 mmHg and maximum increase or decrease from baseline in supine and standing DBP \>=20 mmHg.
TERMINATED
PHASE1
9 participants
Baseline up to 7 to 10 days after last dose
2014-06-04
Participant Flow
Participants who were on a stable dose of donepezil (Aricept) 10 milligram (mg) once daily for at least 30 days before screening and on stable morning dosing at least 14 days before Day 0 were enrolled in this study.
Participant milestones
| Measure |
PF-03654746 and Donepezil
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
2
|
|
Overall Study
COMPLETED
|
7
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Evaluate the Safety, Tolerability, and Blood Levels of PF-03654746 in Subjects With Mild to Moderate Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
45 to 64 years
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Age, Customized
Greater than or equal to (>=) 65 years
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 7 to 10 days after last dosePopulation: Safety population included all participants who took at least 1 dose of study drug.
Criteria for potential clinical concern in vital signs: supine and standing systolic blood pressure (SBP) less than (\<) 90 millimeter of mercury (mmHg), supine and standing diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm, standing pulse rate \<40 bpm or \>140 bpm. Maximum increase or decrease from baseline in supine (Su) and standing (St) SBP \>=30 mmHg and maximum increase or decrease from baseline in supine and standing DBP \>=20 mmHg.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Supine SBP <90 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Standing SBP <90 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Supine DBP <50 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Standing DBP <50 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Supine pulse rate <40 bpm
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Supine pulse rate >120 bpm
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Standing pulse rate <40 bpm
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Standing pulse rate >140 bpm
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Su SBP: Maximum increase from baseline >=30 mmHg
|
3 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
St SBP: Maximum increase from baseline >=30 mmHg
|
1 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Su DBP: Maximum increase from baseline >=20 mmHg
|
2 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
St DBP: Maximum increase from baseline >=20 mmHg
|
1 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Su SBP: Maximum decrease from baseline >=30 mmHg
|
0 participants
|
1 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
St SBP: Maximum decrease from baseline >=30 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
Su DBP: Maximum decrease from baseline >=20 mmHg
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Vital Sign Abnormalities
St DBP: Maximum decrease from baseline >=20 mmHg
|
1 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Baseline up to 7 to 10 days after last dosePopulation: Safety population included all participants who took at least 1 dose of study drug.
Criteria for potential clinical concern in ECG parameters: maximum PR interval of \>=300 milliseconds (msec), maximum QRS interval \>=200 msec, maximum fridericia's corrected QT (QTcF) interval \>=500 msec, PR interval or QRS interval increase from baseline \>=25 percent (%) or 50 percent (%), QTCF interval increase from baseline 30 to 60 msec or \>=60 msec.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
QTCF interval increase from baseline 30 to 60 msec
|
2 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Maximum PR interval >=300 msec
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Maximum QRS Complex >=200 msec
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Maximum QTCF interval >=500 msec
|
1 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
PR interval increase from baseline >=25/50 %
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
QRS complex increase from baseline >=25/50 %
|
0 participants
|
0 participants
|
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
QTCF interval increase from baseline >=60 msec
|
1 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to 7 to 10 days after last dosePopulation: Safety population included all participants who took at least 1 dose of study drug.
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (\< 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/\>1.5\*upper limit of normal \[ULN\]); platelets (\<0.5\*LLN/\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN/\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN), total protein, albumin (\<0.8\*LLN/\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN/\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN/\>1.1\*ULN); urine red blood cells (RBCs), urine white blood cells (WBCs), urine epithelial cells (\>=6 high-powered field), urine bacteria \>20 high-powered field; qualitative urine glucose, ketones, protein values \>=1 in urine dipstick test. Total number of participants with any laboratory abnormalities was reported.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Number of Participants With Clinically Significant Laboratory Test Abnormalities
|
7 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to 7 to 10 days after last dosePopulation: Safety population included all participants who took at least 1 dose of study drug.
Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any potential changes in physical status, as determined by the investigator. Any untoward findings identified on physical exams conducted after the administration of the first dose of study medication was captured as an adverse event.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Physical Examination
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Sleep disturbance
|
23.76 units on a scale
Standard Deviation 21.57
|
15.65 units on a scale
Standard Deviation 22.13
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Somnolence
|
30.49 units on a scale
Standard Deviation 18.40
|
16.70 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Sleep adequacy
|
65.71 units on a scale
Standard Deviation 32.07
|
85.00 units on a scale
Standard Deviation 21.21
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Snore
|
45.71 units on a scale
Standard Deviation 37.80
|
20.00 units on a scale
Standard Deviation 28.28
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Awaken short of breath or with headache
|
8.57 units on a scale
Standard Deviation 15.74
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Quantity of sleep
|
7.86 units on a scale
Standard Deviation 0.90
|
10.50 units on a scale
Standard Deviation 2.12
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Optimal sleep
|
0.71 units on a scale
Standard Deviation 0.49
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Sleep problem index I
|
23.81 units on a scale
Standard Deviation 17.70
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Baseline
Sleep problem index II
|
24.21 units on a scale
Standard Deviation 15.81
|
14.70 units on a scale
Standard Deviation 17.68
|
PRIMARY outcome
Timeframe: Day 5Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Sleep disturbance
|
25.01 units on a scale
Standard Deviation 19.56
|
15.65 units on a scale
Standard Deviation 22.13
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Somnolence
|
28.57 units on a scale
Standard Deviation 26.87
|
16.70 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Sleep adequacy
|
65.71 units on a scale
Standard Deviation 22.25
|
90.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Snore
|
28.57 units on a scale
Standard Deviation 30.24
|
20.00 units on a scale
Standard Deviation 28.28
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Awaken short of breath or with headache
|
8.57 units on a scale
Standard Deviation 22.68
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Quantity of sleep
|
7.57 units on a scale
Standard Deviation 0.98
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Optimal sleep
|
0.71 units on a scale
Standard Deviation 0.49
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Sleep problem index I
|
21.89 units on a scale
Standard Deviation 14.25
|
8.35 units on a scale
Standard Deviation 11.81
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 5
Sleep problem index II
|
24.76 units on a scale
Standard Deviation 14.64
|
13.60 units on a scale
Standard Deviation 16.12
|
PRIMARY outcome
Timeframe: Day 10Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Sleep disturbance
|
27.69 units on a scale
Standard Deviation 27.86
|
13.15 units on a scale
Standard Deviation 18.60
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Somnolence
|
29.53 units on a scale
Standard Deviation 31.46
|
16.70 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Sleep adequacy
|
67.14 units on a scale
Standard Deviation 29.28
|
90.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Snore
|
34.29 units on a scale
Standard Deviation 35.99
|
20.00 units on a scale
Standard Deviation 28.28
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Awaken short of breath or with headache
|
14.29 units on a scale
Standard Deviation 37.80
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Quantity of sleep
|
7.43 units on a scale
Standard Deviation 1.13
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Optimal sleep
|
0.57 units on a scale
Standard Deviation 0.53
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Sleep problem index I
|
26.19 units on a scale
Standard Deviation 20.14
|
8.35 units on a scale
Standard Deviation 11.81
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 10
Sleep problem index II
|
26.90 units on a scale
Standard Deviation 19.49
|
12.50 units on a scale
Standard Deviation 14.57
|
PRIMARY outcome
Timeframe: Day 15Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Sleep disturbance
|
28.76 units on a scale
Standard Deviation 11.58
|
13.15 units on a scale
Standard Deviation 18.60
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Somnolence
|
28.57 units on a scale
Standard Deviation 20.27
|
16.70 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Sleep adequacy
|
64.29 units on a scale
Standard Deviation 31.01
|
90.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Snore
|
40.00 units on a scale
Standard Deviation 41.63
|
20.00 units on a scale
Standard Deviation 28.28
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Awaken short of breath or with headache
|
5.71 units on a scale
Standard Deviation 15.12
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Quantity of sleep
|
7.29 units on a scale
Standard Deviation 0.95
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Optimal sleep
|
0.71 units on a scale
Standard Deviation 0.49
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Sleep problem index I
|
28.10 units on a scale
Standard Deviation 16.55
|
8.35 units on a scale
Standard Deviation 11.81
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 15
Sleep problem index II
|
26.74 units on a scale
Standard Deviation 15.20
|
12.50 units on a scale
Standard Deviation 14.57
|
PRIMARY outcome
Timeframe: Day 20Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Quantity of sleep
|
7.00 units on a scale
Standard Deviation 1.41
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Sleep disturbance
|
23.57 units on a scale
Standard Deviation 22.07
|
5.65 units on a scale
Standard Deviation 7.99
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Somnolence
|
37.14 units on a scale
Standard Deviation 30.75
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Sleep adequacy
|
61.43 units on a scale
Standard Deviation 26.10
|
95.00 units on a scale
Standard Deviation 7.07
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Snore
|
42.86 units on a scale
Standard Deviation 43.86
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Awaken short of breath or with headache
|
8.57 units on a scale
Standard Deviation 15.74
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Optimal sleep
|
0.43 units on a scale
Standard Deviation 0.53
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Sleep problem index I
|
26.19 units on a scale
Standard Deviation 18.11
|
3.35 units on a scale
Standard Deviation 4.74
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 20
Sleep problem index II
|
26.67 units on a scale
Standard Deviation 18.20
|
5.85 units on a scale
Standard Deviation 8.27
|
PRIMARY outcome
Timeframe: Day 25Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Sleep adequacy
|
72.86 units on a scale
Standard Deviation 22.15
|
95.00 units on a scale
Standard Deviation 7.07
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Sleep disturbance
|
23.76 units on a scale
Standard Deviation 21.18
|
3.15 units on a scale
Standard Deviation 4.45
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Somnolence
|
36.19 units on a scale
Standard Deviation 28.24
|
6.65 units on a scale
Standard Deviation 9.40
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Snore
|
45.71 units on a scale
Standard Deviation 47.21
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Awaken short of breath or with headache
|
5.71 units on a scale
Standard Deviation 15.12
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Quantity of sleep
|
7.71 units on a scale
Standard Deviation 0.95
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Optimal sleep
|
0.71 units on a scale
Standard Deviation 0.49
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Sleep problem index I
|
22.37 units on a scale
Standard Deviation 16.86
|
1.65 units on a scale
Standard Deviation 2.33
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 25
Sleep problem index II
|
23.89 units on a scale
Standard Deviation 16.04
|
3.60 units on a scale
Standard Deviation 5.09
|
PRIMARY outcome
Timeframe: Day 30Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Sleep disturbance
|
23.04 units on a scale
Standard Deviation 21.99
|
3.15 units on a scale
Standard Deviation 4.45
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Somnolence
|
37.16 units on a scale
Standard Deviation 24.62
|
6.65 units on a scale
Standard Deviation 9.40
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Sleep adequacy
|
72.86 units on a scale
Standard Deviation 22.15
|
95.00 units on a scale
Standard Deviation 7.07
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Snore
|
42.86 units on a scale
Standard Deviation 43.86
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Awaken short of breath or with headache
|
5.71 units on a scale
Standard Deviation 15.12
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Quantity of sleep
|
7.86 units on a scale
Standard Deviation 1.07
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Optimal sleep
|
0.57 units on a scale
Standard Deviation 0.53
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Sleep problem index I
|
21.90 units on a scale
Standard Deviation 17.52
|
1.65 units on a scale
Standard Deviation 2.33
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Day 30
Sleep problem index II
|
23.26 units on a scale
Standard Deviation 16.21
|
3.60 units on a scale
Standard Deviation 5.09
|
PRIMARY outcome
Timeframe: Follow-up (7 to 10 days after last dose)Population: Safety population included all participants who took at least 1 dose of study drug.
Participant-rated 12-item questionnaire to assess sleep quality and quantity. The items contribute to each scale and are averaged to create the 7 subscale scores: sleep disturbance, snoring, awaken short of breath (ASoB) or with a headache, somnolence, sleep adequacy, sleep quantity (range 0 to 24) and optimal sleep (yes: 1, no: 0), and overall sleep problem index (SPI) I and II. Except for sleep quantity and optimal sleep, scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. Except for sleep quantity, sleep adequacy and optimal sleep, higher scores=greater impairment. Scales with at least one item answered was used to generate a scale score.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Sleep disturbance
|
16.44 units on a scale
Standard Deviation 17.07
|
3.15 units on a scale
Standard Deviation 4.45
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Somnolence
|
32.39 units on a scale
Standard Deviation 27.62
|
6.65 units on a scale
Standard Deviation 9.40
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Sleep adequacy
|
72.86 units on a scale
Standard Deviation 23.60
|
95.00 units on a scale
Standard Deviation 7.07
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Snore
|
42.86 units on a scale
Standard Deviation 43.86
|
10.00 units on a scale
Standard Deviation 14.14
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Awaken short of breath or with headache
|
5.71 units on a scale
Standard Deviation 15.12
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Quantity of sleep
|
8.14 units on a scale
Standard Deviation 0.69
|
9.50 units on a scale
Standard Deviation 0.71
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Optimal sleep
|
0.71 units on a scale
Standard Deviation 0.49
|
0.00 units on a scale
Standard Deviation 0.00
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Sleep problem index I
|
17.61 units on a scale
Standard Deviation 15.25
|
1.65 units on a scale
Standard Deviation 2.33
|
|
Medical Outcomes Study - Sleep Scale (MOS-SS) Score at Follow-up
Sleep problem index II
|
19.67 units on a scale
Standard Deviation 14.12
|
3.60 units on a scale
Standard Deviation 5.09
|
PRIMARY outcome
Timeframe: Baseline, Day 5Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 5
Baseline
|
4.1 units on a scale
Standard Deviation 6.09
|
3.0 units on a scale
Standard Deviation 4.24
|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 5
Change at Day 5
|
-1.9 units on a scale
Standard Deviation 5.64
|
-1.0 units on a scale
Standard Deviation 1.41
|
PRIMARY outcome
Timeframe: Baseline, Day 10Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 10
|
-1.7 units on a scale
Standard Deviation 4.75
|
-1.0 units on a scale
Standard Deviation 1.41
|
PRIMARY outcome
Timeframe: Baseline, Day 15Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 15
|
-2.6 units on a scale
Standard Deviation 4.39
|
-1.0 units on a scale
Standard Deviation 1.41
|
PRIMARY outcome
Timeframe: Baseline, Day 20Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 20
|
-2.7 units on a scale
Standard Deviation 5.71
|
0.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Day 25Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 25
|
-2.6 units on a scale
Standard Deviation 4.39
|
0.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Day 30Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Day 30
|
-1.4 units on a scale
Standard Deviation 5.22
|
0.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Follow-up (7 to 10 days after last dose)Population: Safety population included all participants who took at least 1 dose of study drug.
NPI: 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, night-time behavior. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Follow-up
|
-2.6 units on a scale
Standard Deviation 4.39
|
1.5 units on a scale
Standard Deviation 2.12
|
PRIMARY outcome
Timeframe: Baseline, Day 5Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 5
Baseline
|
24.6 units on a scale
Standard Deviation 1.51
|
24.0 units on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 5
Change at Day 5
|
-0.7 units on a scale
Standard Deviation 2.29
|
3.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Day 10Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 10
|
0.1 units on a scale
Standard Deviation 2.34
|
3.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Day 15Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 15
|
1.3 units on a scale
Standard Deviation 1.80
|
2.5 units on a scale
Standard Deviation 0.71
|
PRIMARY outcome
Timeframe: Baseline, Day 20Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 20
|
0.4 units on a scale
Standard Deviation 2.94
|
4.0 units on a scale
Standard Deviation 0.00
|
PRIMARY outcome
Timeframe: Baseline, Day 25Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 25
|
1.0 units on a scale
Standard Deviation 2.08
|
3.5 units on a scale
Standard Deviation 0.71
|
PRIMARY outcome
Timeframe: Baseline, Day 30Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Day 30
|
0.6 units on a scale
Standard Deviation 2.37
|
3.0 units on a scale
Standard Deviation 2.83
|
PRIMARY outcome
Timeframe: Baseline, Follow-up (7 to 10 days after last dose)Population: Safety population included all participants who took at least 1 dose of study drug.
MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Follow-up
|
0.7 units on a scale
Standard Deviation 1.60
|
3.0 units on a scale
Standard Deviation 4.24
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30Population: Pharmacokinetic (PK) parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-03654746
|
118.6 nanogram hour per milliliter (ng*hr/mL)
Standard Deviation 35.687
|
—
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30Population: PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) for PF-03654746
|
9.430 nanogran per millileter (ng/mL)
Standard Deviation 2.7317
|
—
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8 and 12 hours post-dose on Day 30Population: PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Time to Reach Maximum Observed Serum Concentration (Tmax) for PF-03654746
|
3.00 hours
Interval 1.0 to 3.0
|
—
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30Population: PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Donepezil
Day 0
|
881.6 ng*hr/mL
Standard Deviation 282.03
|
1109 ng*hr/mL
Standard Deviation 176.07
|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Donepezil
Day 30
|
1035 ng*hr/mL
Standard Deviation 364.62
|
1013 ng*hr/mL
Standard Deviation 91.217
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30Population: PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for Donepezil
Day 0
|
45.47 ng/mL
Standard Deviation 12.847
|
53.89 ng/mL
Standard Deviation 10.465
|
|
Maximum Plasma Concentration (Cmax) for Donepezil
Day 30
|
50.28 ng/mL
Standard Deviation 14.864
|
49.73 ng/mL
Standard Deviation 1.7678
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 0.5, 1, 3, 8, 12 hours post-dose on Day 0, Day 30Population: PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest during the study.
Outcome measures
| Measure |
PF-03654746 and Donepezil
n=7 Participants
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 Participants
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Donepezil
Day 30
|
3.00 hours
Interval 2.98 to 12.0
|
2.98 hours
Interval 2.98 to 2.98
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Donepezil
Day 0
|
2.98 hours
Interval 0.967 to 3.0
|
2.99 hours
Interval 2.98 to 3.0
|
Adverse Events
PF-03654746 and Donepezil
Placebo and Donepezil
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF-03654746 and Donepezil
n=7 participants at risk
PF-03654746 0.25 milligram (mg) powder in capsule orally once daily on Day 1 to 5, followed by PF-03654746 0.5 mg powder in capsule orally once daily on Day 6 to 10 and PF-03654746 1 mg powder in capsule orally once daily on Day 11 to 15 during the forced titration phase. PF-03654746 0.5 mg to 2 mg powder in capsule orally once daily, based on investigator's discretion and tolerability, on Day 16 to 30 during the flexible titration phase. Background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
Placebo and Donepezil
n=2 participants at risk
Placebo matched to PF-03654746 powder in capsule once daily on Day 1 to 30 along with background donepezil (Aricept) 10 mg tablet orally once daily throughout the study.
|
|---|---|---|
|
Nervous system disorders
Headache
|
14.3%
1/7
|
0.00%
0/2
|
|
Psychiatric disorders
Abnormal dreams
|
14.3%
1/7
|
0.00%
0/2
|
|
Psychiatric disorders
Euphoric mood
|
14.3%
1/7
|
0.00%
0/2
|
|
Psychiatric disorders
Hypnagogic hallucination
|
14.3%
1/7
|
0.00%
0/2
|
|
Psychiatric disorders
Illusion
|
14.3%
1/7
|
0.00%
0/2
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
14.3%
1/7
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
1/7
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.3%
1/7
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
14.3%
1/7
|
0.00%
0/2
|
Additional Information
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