Trial Outcomes & Findings for A Brief Study To Evaluate The Safety, Tolerability, And Blood Levels Of Multiple Doses Of PF-044467943 Or Placebo In Combination With Donepezil In Subjects With Mild To Moderate Alzheimer's Disease (NCT NCT00988598)
NCT ID: NCT00988598
Last Updated: 2020-11-19
Results Overview
Criteria for vital signs abnormalities of potential concern included: supine/standing systolic blood pressure (BP) (less than \[\<\] 90 millimeter of mercury \[mmHg\], maximum \[max\] decrease and increase of greater than or equal to \[\>=\] 30 mmHg from baseline); diastolic BP (\<50 mmHg, maximum decrease and increase of \>=20 mmHg from baseline); supine pulse rate \<40 beats per minute \[bpm\] or greater than \[\>\]120 bpm); standing pulse rate \<40 bpm or \>140 bpm. Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
COMPLETED
PHASE1
15 participants
Baseline up to Day 10
2020-11-19
Participant Flow
Eligible participants enrolled in this study were already on prior stable donepezil therapy.
Participant milestones
| Measure |
PF-04447943 25 mg + Donepezil
PF-04447943 25 milligram (mg) tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
5
|
|
Overall Study
COMPLETED
|
8
|
5
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
PF-04447943 25 mg + Donepezil
PF-04447943 25 milligram (mg) tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
A Brief Study To Evaluate The Safety, Tolerability, And Blood Levels Of Multiple Doses Of PF-044467943 Or Placebo In Combination With Donepezil In Subjects With Mild To Moderate Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.9 years
STANDARD_DEVIATION 5.6 • n=5 Participants
|
69.8 years
STANDARD_DEVIATION 5.8 • n=7 Participants
|
69.9 years
STANDARD_DEVIATION 5.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 10Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
Criteria for vital signs abnormalities of potential concern included: supine/standing systolic blood pressure (BP) (less than \[\<\] 90 millimeter of mercury \[mmHg\], maximum \[max\] decrease and increase of greater than or equal to \[\>=\] 30 mmHg from baseline); diastolic BP (\<50 mmHg, maximum decrease and increase of \>=20 mmHg from baseline); supine pulse rate \<40 beats per minute \[bpm\] or greater than \[\>\]120 bpm); standing pulse rate \<40 bpm or \>140 bpm. Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Supine Systolic BP (<90 mmHg)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Standing Systolic BP (<90 mmHg)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Supine Diastolic BP (<50 mmHg)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Standing Diastolic BP (<50 mmHg)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Increase in Supine Systolic BP (>=30 mmHg)
|
0 participants
|
2 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Increase in Standing Systolic BP (>=30 mmHg)
|
0 participants
|
2 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Increase in Supine Diastolic BP (>=20 mmHg)
|
1 participants
|
1 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Increase in Standing Diastolic BP (>=20 mmHg)
|
0 participants
|
1 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Decrease in Supine Systolic BP (>=30 mmHg)
|
2 participants
|
1 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Decrease in Standing Systolic BP (>=30 mmHg)
|
2 participants
|
1 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Decrease in Supine Diastolic BP (>=20 mmHg)
|
0 participants
|
1 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Max Decrease in Standing Diastolic BP (>=20 mmHg)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Supine Pulse Rate (<40 bpm)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Supine Pulse Rate (>120 bpm)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Standing Pulse Rate (<40 bpm)
|
0 participants
|
0 participants
|
|
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Standing Pulse Rate (>140 bpm)
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 10Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
Criteria for ECG abnormalities of potential clinical concern included: PR interval (\>=300 milliseconds \[msec\], \>= 25 percent \[%\] increase when baseline \>200 msec or increase \>=50% when baseline less than or equal to \[\<=\] 200 msec); QRS interval (\>=200 msec, \>= 25% increase when baseline \>100 msec or increase \>=50% when baseline \<=100 msec); QT corrected using Fridericia's formula (QTcF) (\>=500 msec, maximum increase between \>=30 to \<60 msec and \>=60 msec). Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum PR Interval (>=300 msec)
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum PR Interval Increase (>=25/50%)
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum QRS Interval (>=200 msec)
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum QRS Interval Increase (>=25/50%)
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum QTcF Interval (>=500 msec)
|
0 participants
|
0 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum QTcF Interval Increase(Change >=30 to <60)
|
2 participants
|
1 participants
|
|
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Maximum QTcF Interval Increase (Change >=60)
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 10Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit (\<0.8\*lower limit of normal \[LLN\]); red blood cell count (\<0.8\*LLN); platelets (\<0.5\*LLN or \>1.75\* upper limit of normal \[ULN\]); leucocytes (\<0.6\*LLN or \>1.5\*ULN); lymphocytes, total neutrophils (\<0.8\*LLN or \>1.2\*ULN); basophils, eosinophils, monocytes (\>1.2\*ULN); total bilirubin (\>1.5\* ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (\>3\*ULN); creatinine, blood urea nitrogen (\>1.3\*ULN); glucose (\<0.6\*LLN or \>1.5\*ULN); uric acid (\>1.2\*ULN); sodium (\<0.95\*LLN or 1.05\*ULN); potassium, calcium, chloride, bicarbonate (\<0.9\*LLN or 1.1\*ULN); albumin, total protein (\<0.8\*LLN or 1.2\*ULN); urine analysis. Total number of participants with any laboratory abnormalities was reported.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities
|
4 participants
|
4 participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 10Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 10 after last dose that were absent before treatment or that worsened relative to pretreatment state. Any abnormalities related to physical and neurological findings, laboratory tests, vital signs and ECG were reported as adverse events. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
6 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7Population: Pharmacokinetic (PK) concentration analysis set included all randomized participants who had received at least one dose of PF-04447943 and had at least 1 evaluable PF-04447943 concentration. Here, 'number analyzed, n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Plasma Concentrations of PF-04447943
Day 7: 0.5 hours
|
340.4 nanogram per milliliter (ng/mL)
Standard Deviation 168.41
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 0 hours
|
0.01050 nanogram per milliliter (ng/mL)
Standard Deviation 0.033204
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 0.5 hours
|
179.6 nanogram per milliliter (ng/mL)
Standard Deviation 127.67
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 1 hour
|
296.7 nanogram per milliliter (ng/mL)
Standard Deviation 83.312
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 3 hours
|
225.9 nanogram per milliliter (ng/mL)
Standard Deviation 46.905
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 8 hours
|
91.76 nanogram per milliliter (ng/mL)
Standard Deviation 30.400
|
—
|
|
Plasma Concentrations of PF-04447943
Day 1: 12 hours
|
51.99 nanogram per milliliter (ng/mL)
Standard Deviation 21.018
|
—
|
|
Plasma Concentrations of PF-04447943
Day 7: 0 hours
|
73.49 nanogram per milliliter (ng/mL)
Standard Deviation 28.023
|
—
|
|
Plasma Concentrations of PF-04447943
Day 7: 1 hour
|
353.6 nanogram per milliliter (ng/mL)
Standard Deviation 112.63
|
—
|
|
Plasma Concentrations of PF-04447943
Day 7: 3 hours
|
284.0 nanogram per milliliter (ng/mL)
Standard Deviation 83.881
|
—
|
|
Plasma Concentrations of PF-04447943
Day 7: 8 hours
|
124.8 nanogram per milliliter (ng/mL)
Standard Deviation 49.247
|
—
|
|
Plasma Concentrations of PF-04447943
Day 7: 12 hours
|
69.08 nanogram per milliliter (ng/mL)
Standard Deviation 28.483
|
—
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7Population: PK analysis set included all randomized participants who had received at least one dose of PF-04447943 and had at least 1 of the PK parameters of interest for PF-04447943. Here, 'n' signifies those participants who were evaluable at specified time point.
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943
Day 1
|
1657 nanogram*hour per milliliter (ng*hr/mL)
Standard Deviation 391.88
|
—
|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943
Day 7
|
2140 nanogram*hour per milliliter (ng*hr/mL)
Standard Deviation 688.96
|
—
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7Population: PK analysis set included all randomized participants who had received at least one dose of PF-04447943 and had at least 1 of the PK parameters of interest for PF-04447943. Here, 'n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Day 1
|
303.8 ng/mL
Standard Deviation 66.655
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Day 7
|
390.9 ng/mL
Standard Deviation 109.31
|
—
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7Population: PK analysis set included all randomized participants who had received at least one dose of PF-04447943 and had at least 1 of the PK parameters of interest for PF-04447943. Here, 'n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Day 1
|
1.00 hours
Interval 1.0 to 3.0
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Day 7
|
0.767 hours
Interval 0.5 to 3.0
|
—
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7Population: PK concentration analysis set included all randomized participants who had received donepezil and had at least 1 evaluable donepezil concentration. Here, 'n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Plasma Concentrations of Donepezil
Day 0: 0 hours
|
29.30 ng/mL
Standard Deviation 22.982
|
19.10 ng/mL
Standard Deviation 10.562
|
|
Plasma Concentrations of Donepezil
Day 0: 0.5 hours
|
29.93 ng/mL
Standard Deviation 22.874
|
23.92 ng/mL
Standard Deviation 16.478
|
|
Plasma Concentrations of Donepezil
Day 0: 1 hour
|
41.08 ng/mL
Standard Deviation 20.592
|
36.18 ng/mL
Standard Deviation 9.6916
|
|
Plasma Concentrations of Donepezil
Day 0: 3 hours
|
54.09 ng/mL
Standard Deviation 28.122
|
41.56 ng/mL
Standard Deviation 11.088
|
|
Plasma Concentrations of Donepezil
Day 0: 8 hours
|
42.15 ng/mL
Standard Deviation 24.360
|
30.92 ng/mL
Standard Deviation 11.339
|
|
Plasma Concentrations of Donepezil
Day 0: 12 hours
|
34.04 ng/mL
Standard Deviation 20.659
|
28.02 ng/mL
Standard Deviation 11.308
|
|
Plasma Concentrations of Donepezil
Day 7: 0 hours
|
34.94 ng/mL
Standard Deviation 22.579
|
33.86 ng/mL
Standard Deviation 3.7031
|
|
Plasma Concentrations of Donepezil
Day 7: 0.5 hours
|
39.56 ng/mL
Standard Deviation 26.766
|
35.82 ng/mL
Standard Deviation 3.8226
|
|
Plasma Concentrations of Donepezil
Day 7: 1 hour
|
47.29 ng/mL
Standard Deviation 30.726
|
45.04 ng/mL
Standard Deviation 12.347
|
|
Plasma Concentrations of Donepezil
Day 7: 3 hours
|
58.15 ng/mL
Standard Deviation 30.916
|
56.36 ng/mL
Standard Deviation 5.6783
|
|
Plasma Concentrations of Donepezil
Day 7: 8 hours
|
46.90 ng/mL
Standard Deviation 23.802
|
45.42 ng/mL
Standard Deviation 4.4404
|
|
Plasma Concentrations of Donepezil
Day 7: 12 hours
|
42.83 ng/mL
Standard Deviation 23.299
|
41.78 ng/mL
Standard Deviation 4.7505
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7Population: PK analysis set included all randomized participants who had received donepezil and had at least 1 of the PK parameters of interest of donepezil. Here, 'n' signifies those participants who were evaluable at specified time point.
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil
Day 0
|
426.8 ng*hr/mL
Standard Deviation 256.08
|
380.6 ng*hr/mL
Standard Deviation 127.02
|
|
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil
Day 7
|
513.4 ng*hr/mL
Standard Deviation 314.66
|
565.2 ng*hr/mL
Standard Deviation 40.402
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7Population: PK analysis set included all randomized participants who had received donepezil and had at least 1 of the PK parameters of interest of donepezil. Here, 'n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Donepezil
Day 7
|
52.88 ng/mL
Standard Deviation 30.177
|
59.61 ng/mL
Standard Deviation 4.6404
|
|
Maximum Observed Plasma Concentration (Cmax) of Donepezil
Day 0
|
47.60 ng/mL
Standard Deviation 27.600
|
42.48 ng/mL
Standard Deviation 8.1522
|
SECONDARY outcome
Timeframe: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7Population: PK analysis set included all randomized participants who had received donepezil and had at least 1 of the PK parameters of interest of donepezil. Here, 'n' signifies those participants who were evaluable at specified time point.
Outcome measures
| Measure |
PF-04447943 25 mg + Donepezil
n=10 Participants
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 Participants
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil
Day 0
|
3.00 hours
Interval 1.0 to 3.0
|
3.00 hours
Interval 1.0 to 3.02
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil
Day 7
|
3.00 hours
Interval 1.0 to 8.0
|
3.00 hours
Interval 1.0 to 3.0
|
Adverse Events
PF-04447943 25 mg + Donepezil
Placebo + Donepezil
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF-04447943 25 mg + Donepezil
n=10 participants at risk
PF-04447943 25 mg tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
Placebo + Donepezil
n=5 participants at risk
Placebo matched to PF-04447943 tablet orally, twice daily from Day 1 through Day 6 and once in morning on Day 7 along with donepezil 10 mg tablet orally once daily for 7 days.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
10.0%
1/10
|
0.00%
0/5
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
2/10
|
0.00%
0/5
|
|
Gastrointestinal disorders
Nausea
|
20.0%
2/10
|
0.00%
0/5
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10
|
0.00%
0/5
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10
|
0.00%
0/5
|
|
Nervous system disorders
Headache
|
40.0%
4/10
|
0.00%
0/5
|
|
Psychiatric disorders
Confusional state
|
10.0%
1/10
|
0.00%
0/5
|
|
Psychiatric disorders
Nightmare
|
10.0%
1/10
|
0.00%
0/5
|
|
Renal and urinary disorders
Pollakiuria
|
10.0%
1/10
|
0.00%
0/5
|
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