Alzheimer's Disease
Conditions
Keywords
phase 1 Alzheimer's disease donepezil
Brief summary
The purpose of the study is to evaluate the safety of PF-04447943 when given in combination with donepezil in subjects who have Alzheimer's Disease. The study will also evaluate the absorption and distribution of both PF-04447943 and donepezil.
Interventions
DRUGPF-04447943
25 mg of PF-04447943 orally every 12 hours for 7 days
DRUGPlacebo
25 mg matching placebo to PF-04447943 orally every 12 hours for 7 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have Alzheimer's dementia with a Mini Mental State Examination score between 18-26, inclusive. * Subjects must have a reliable caregiver. * Subjects must be on Aricept * Memantine is allowed if subjects are on a stable dose * Subjects must be in reasonably good health, based on medical history, physical examination, vital signs, and ECG, with no serious or unstable disease within the past 3 months.
Exclusion criteria
* Subjects with clinically significant heart disease cannot participate. * Subjects with a past or current history of seizures cannot participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Baseline up to Day 10 | 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. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Baseline up to Day 10 | 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. |
| Number of Participants With Laboratory Test Abnormalities | Baseline up to Day 10 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Day 10 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of Donepezil | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7 | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7 | Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours. |
| Plasma Concentrations of PF-04447943 | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7 | — |
| Maximum Observed Plasma Concentration (Cmax) of Donepezil | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7 | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943 | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7 | Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours. |
| Maximum Observed Plasma Concentration (Cmax) of PF-04447943 | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943 | 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7 | — |
Countries
United States
Participant flow
Pre-assignment details
Eligible participants enrolled in this study were already on prior stable donepezil therapy.
Participants by arm
| Arm | Count |
|---|---|
| PF-04447943 25 mg + Donepezil 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. | 10 |
| 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. | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | PF-04447943 25 mg + Donepezil | Placebo + Donepezil | Total |
|---|---|---|---|
| Age, Continuous | 69.9 years STANDARD_DEVIATION 5.6 | 69.8 years STANDARD_DEVIATION 5.8 | 69.9 years STANDARD_DEVIATION 5.4 |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
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.
Time frame: Baseline up to Day 10
Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QRS Interval Increase (>=25/50%) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QRS Interval (>=200 msec) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval Increase (Change >=60) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum PR Interval (>=300 msec) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval (>=500 msec) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval Increase(Change >=30 to <60) | 2 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum PR Interval Increase (>=25/50%) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval Increase (Change >=60) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum PR Interval Increase (>=25/50%) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QRS Interval (>=200 msec) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QRS Interval Increase (>=25/50%) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval (>=500 msec) | 0 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum QTcF Interval Increase(Change >=30 to <60) | 1 participants |
| Placebo + Donepezil | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern | Maximum PR Interval (>=300 msec) | 0 participants |
Primary
Number of Participants With Laboratory Test Abnormalities
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.
Time frame: Baseline up to Day 10
Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04447943 25 mg + Donepezil | Number of Participants With Laboratory Test Abnormalities | 4 participants |
| Placebo + Donepezil | Number of Participants With Laboratory Test Abnormalities | 4 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline up to Day 10
Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Placebo + Donepezil | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Placebo + Donepezil | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
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.
Time frame: Baseline up to Day 10
Population: Safety analysis set included all participants who had received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Supine Systolic BP (>=30 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Pulse Rate (<40 bpm) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Supine Diastolic BP (>=20 mmHg) | 1 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Diastolic BP (<50 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Standing Diastolic BP (>=20 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Diastolic BP (<50 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Systolic BP (<90 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Supine Systolic BP (>=30 mmHg) | 2 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Standing Systolic BP (>=30 mmHg) | 2 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Supine Diastolic BP (>=20 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Standing Systolic BP (>=30 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Standing Diastolic BP (>=20 mmHg) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Pulse Rate (<40 bpm) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Pulse Rate (>120 bpm) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Pulse Rate (>140 bpm) | 0 participants |
| PF-04447943 25 mg + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Systolic BP (<90 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Pulse Rate (>140 bpm) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Systolic BP (<90 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Systolic BP (<90 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Diastolic BP (<50 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Supine Systolic BP (>=30 mmHg) | 2 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Standing Systolic BP (>=30 mmHg) | 2 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Standing Diastolic BP (>=20 mmHg) | 1 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Standing Diastolic BP (>=20 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Pulse Rate (>120 bpm) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Standing Pulse Rate (<40 bpm) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Diastolic BP (<50 mmHg) | 0 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Increase in Supine Diastolic BP (>=20 mmHg) | 1 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Supine Systolic BP (>=30 mmHg) | 1 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Standing Systolic BP (>=30 mmHg) | 1 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Max Decrease in Supine Diastolic BP (>=20 mmHg) | 1 participants |
| Placebo + Donepezil | Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern | Supine Pulse Rate (<40 bpm) | 0 participants |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | 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 |
| PF-04447943 25 mg + Donepezil | 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 |
| Placebo + Donepezil | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil | Day 0 | 380.6 ng*hr/mL | Standard Deviation 127.02 |
| Placebo + Donepezil | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil | Day 7 | 565.2 ng*hr/mL | Standard Deviation 40.402 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | 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 |
| PF-04447943 25 mg + Donepezil | 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
Maximum Observed Plasma Concentration (Cmax) of Donepezil
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Maximum Observed Plasma Concentration (Cmax) of Donepezil | Day 0 | 47.60 ng/mL | Standard Deviation 27.6 |
| PF-04447943 25 mg + Donepezil | Maximum Observed Plasma Concentration (Cmax) of Donepezil | Day 7 | 52.88 ng/mL | Standard Deviation 30.177 |
| Placebo + Donepezil | Maximum Observed Plasma Concentration (Cmax) of Donepezil | Day 0 | 42.48 ng/mL | Standard Deviation 8.1522 |
| Placebo + Donepezil | Maximum Observed Plasma Concentration (Cmax) of Donepezil | Day 7 | 59.61 ng/mL | Standard Deviation 4.6404 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Maximum Observed Plasma Concentration (Cmax) of PF-04447943 | Day 1 | 303.8 ng/mL | Standard Deviation 66.655 |
| PF-04447943 25 mg + Donepezil | Maximum Observed Plasma Concentration (Cmax) of PF-04447943 | Day 7 | 390.9 ng/mL | Standard Deviation 109.31 |
Secondary
Plasma Concentrations of Donepezil
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 1 hour | 41.08 ng/mL | Standard Deviation 20.592 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 0.5 hours | 39.56 ng/mL | Standard Deviation 26.766 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 8 hours | 42.15 ng/mL | Standard Deviation 24.36 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 1 hour | 47.29 ng/mL | Standard Deviation 30.726 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 0.5 hours | 29.93 ng/mL | Standard Deviation 22.874 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 3 hours | 58.15 ng/mL | Standard Deviation 30.916 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 12 hours | 34.04 ng/mL | Standard Deviation 20.659 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 8 hours | 46.90 ng/mL | Standard Deviation 23.802 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 0 hours | 29.30 ng/mL | Standard Deviation 22.982 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 0: 3 hours | 54.09 ng/mL | Standard Deviation 28.122 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 12 hours | 42.83 ng/mL | Standard Deviation 23.299 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of Donepezil | Day 7: 0 hours | 34.94 ng/mL | Standard Deviation 22.579 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 12 hours | 41.78 ng/mL | Standard Deviation 4.7505 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 0.5 hours | 23.92 ng/mL | Standard Deviation 16.478 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 1 hour | 36.18 ng/mL | Standard Deviation 9.6916 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 3 hours | 41.56 ng/mL | Standard Deviation 11.088 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 8 hours | 30.92 ng/mL | Standard Deviation 11.339 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 12 hours | 28.02 ng/mL | Standard Deviation 11.308 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 0 hours | 33.86 ng/mL | Standard Deviation 3.7031 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 0.5 hours | 35.82 ng/mL | Standard Deviation 3.8226 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 1 hour | 45.04 ng/mL | Standard Deviation 12.347 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 3 hours | 56.36 ng/mL | Standard Deviation 5.6783 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 7: 8 hours | 45.42 ng/mL | Standard Deviation 4.4404 |
| Placebo + Donepezil | Plasma Concentrations of Donepezil | Day 0: 0 hours | 19.10 ng/mL | Standard Deviation 10.562 |
Secondary
Plasma Concentrations of PF-04447943
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 0 hours | 0.01050 nanogram per milliliter (ng/mL) | Standard Deviation 0.033204 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 0.5 hours | 179.6 nanogram per milliliter (ng/mL) | Standard Deviation 127.67 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 1 hour | 296.7 nanogram per milliliter (ng/mL) | Standard Deviation 83.312 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 3 hours | 225.9 nanogram per milliliter (ng/mL) | Standard Deviation 46.905 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 8 hours | 91.76 nanogram per milliliter (ng/mL) | Standard Deviation 30.4 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 1: 12 hours | 51.99 nanogram per milliliter (ng/mL) | Standard Deviation 21.018 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 0 hours | 73.49 nanogram per milliliter (ng/mL) | Standard Deviation 28.023 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 0.5 hours | 340.4 nanogram per milliliter (ng/mL) | Standard Deviation 168.41 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 1 hour | 353.6 nanogram per milliliter (ng/mL) | Standard Deviation 112.63 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 3 hours | 284.0 nanogram per milliliter (ng/mL) | Standard Deviation 83.881 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 8 hours | 124.8 nanogram per milliliter (ng/mL) | Standard Deviation 49.247 |
| PF-04447943 25 mg + Donepezil | Plasma Concentrations of PF-04447943 | Day 7: 12 hours | 69.08 nanogram per milliliter (ng/mL) | Standard Deviation 28.483 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil | Day 0 | 3.00 hours |
| PF-04447943 25 mg + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil | Day 7 | 3.00 hours |
| Placebo + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil | Day 0 | 3.00 hours |
| Placebo + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil | Day 7 | 3.00 hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-04447943 25 mg + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943 | Day 1 | 1.00 hours |
| PF-04447943 25 mg + Donepezil | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943 | Day 7 | 0.767 hours |