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PF-04447943

Phase 2

Alzheimer's Disease | Small molecule | Neurology |Pfizer, Inc.|Last Updated: Nov 19, 2020

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials2
Total Enrollment206

FDA Designations

No designations recorded

Clinical trial landscape

PF-04447943 · 7 trials · 3 indications

Phase 2 1Phase 1 6
NCT00930059A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's DiseaseAlzheimer's Disease
COMPLETED191 Analytics
PHASE2COMPLETED
A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline
Baseline (Day 1)

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 12
Baseline, Week 12

ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 0.5 Hour Post-Dose
0.5 hour post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 1 Hour Post-Dose
1 hour post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 2 Hours Post-Dose
2 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 3 Hours Post-Dose
3 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 4 Hours Post-Dose
4 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 8 Hours Post-Dose
8 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 12 Hours Post-Dose
12 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Time-Matched Mean Difference in Corrected QT Interval Using Fridericia's Correction Method (QTcF) for PF-04447943 and Placebo at 24 Hours Post-Dose
24 hours post-dose

Least square mean of QTcF measure for each reporting arm has been reported in summary or descriptive statistics. Least square mean difference across PF-04447943 25 mg and placebo; PF-04447943 100 mg and placebo is reported in statistical analysis.

Steady state PF 04447943 Cmax and AUCtau.
up through day 44
Steady state Donepezil Cmax and AUCtau.
up through day 44
Safety endpoints include vital signs, ECGs, clinical laboratory tests, clinical examinations, and adverse events.
up through day 44
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.

AEs (spontaneous and solicited). Change from baseline in vital signs.
Day 0 to follow up visit after Study Day 5(single dose arm) and Day 11(multiple dose arm)
ECG and clinical safety laboratory endpoints, including a complete blood count, a full chemistry panel (including electrolytes and hepatic transaminases) and urinalysis.
Screening visit to follow up visit after Study Day 5(single dose arm) and Day 11(multiple dose arm)
Pharmacokinetic (single): AUClast, Cmax, Tmax
Day 1 to day 5
Pharmacokinetic(multiple): AUCt, Cmax and Tmax on Days 1 and 7, and Ctrough on Days 2, 3, 4 and 7.
Day 1 to day 11
Pharmacokinetic endpoints include plasma PF-04447943 area under the curve (AUC), maximum plasma concentration (Cmax) and time of maximum plasma concentration (Tmax).
Up to 96 hours after drug administration
Safety endpoints include vital signs, ECGs, clinical laboratory tests, clinical evaluations and examinations, and adverse events.
Up to 96 hours after drug administration
Safety endpoints include evaluation of adverse events, change from baseline in vital signs, triplicate and single ECGs, and clinical safety laboratory tests
For cohorts 1-3, up to 17 days; for cohort 4, up to 24 days.
Pharmacokinetic endpoints include plasma PF-04447943 area udner the curve (AUCt ), maximum plasma concentration (Cmax) and time of maximum plasma concentration (Tmax)
For cohorts 1-3, days 1 and 7; for cohort 4, days 1 and 14
Maximum plasma concentration (Cmax)
1 hour post dose day 4
Minimum plasma concentration ((Ctrough)
For cohorts 1-3, days 2, 3, 4, and 7; for cohort 4, days 2, 3, 4, 12, and 13
Fraction of the total dose excreted in urine (Fe) and the renal clearance (CLR), and, if the data permit, half-life and the observed exposure accumulation ratio (Ro), and fluctuation index (Cmax: Cmin ratio) following multiple doses
For cohorts 1-3, day 7; for cohort 4, day 14

Secondary Endpoints

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9
Baseline, Week 3, 6, 9
Clinical Global Impression - Improvement (CGI-I)
Week 3, 6, 9, 12
Neuropsychiatric Inventory (NPI) Total Score at Baseline
Baseline
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PF-04447943EXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
PF-04447943 low doseEXPERIMENTAL25 mg of PF-04447943
PF-04447943 high doseEXPERIMENTAL100 mg of PF-04447943
MoxifloxacinACTIVE_COMPARATOR400 mg of moxifloxacin
Active PF-04447943EXPERIMENTAL -
Placebo PF-04447943PLACEBO_COMPARATOR -
Single doseEXPERIMENTAL3 way crossover with randomized placebo substitution to evaluate single escalating oral doses of PF 04447943 in 9 healthy young adult subjects.
Multiple doseEXPERIMENTAL3:1 active PF 04447943 to placebo randomization in 8 healthy elderly subjects.
Sequence 1EXPERIMENTAL -
Sequence 2EXPERIMENTAL -
Cohort 1EXPERIMENTALSubjects will be randomized to receive either experimental drug (n=6) or placebo (n=2).
Cohort 2EXPERIMENTALSubjects will be randomized to receive either experimental drug (n=6) or placebo (n=2).
Cohort 3aEXPERIMENTALSubjects will be randomized to receive either experimental drug (n=3) or placebo (n=1).
Cohort 3bEXPERIMENTALSubjects will be randomized to receive either experimental drug (n=3) or placebo (n=1).
Cohort 4EXPERIMENTAL -

Interventions

NameTypeDescription
PF-04447943DRUGtablets, 25 mg every 12 hours for 12 wks
PlaceboDRUGmatching placebo tablets, every 12 hours for 12 wks
MoxifloxacinDRUGSingle oral dose of moxifloxacin administered as tablet
PF-04447943 25 mgDRUG25 mg PF-04447943 BID for 7 days (period 1) 7 day washout (no drug) 7 days of 5 mg donepezil QD; 14 days 10 mg QD (Period 2) 7 days of 10 mg donepezil QD and 25 mg PF-04447943 BID (Period 3)
Placebo PFDRUGPlacebo BID for 7 days (period 1) 7 day washout (no drug) 7 days of 5 mg donepezil QD; 14 days 10 mg QD (Period 2) 7 days of 10 mg donepezil QD and Placebo BID (Period 3)
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Eligibility Criteria

Age Range55 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites44

Inclusion Criteria: * Mild to moderate Alzheimer's disease (MMSE 14-26) * Good general health (such controlled conditions as Type 2 diabetes and hypertension allowed) Exclusion Criteria: * Use of acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine within 12 week...

Countries:United StatesCanadaChileCzechiaSingapore
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Frequently asked questions about PF-04447943

What is PF-04447943 used for?

PF-04447943 is an investigational small molecule being developed by Pfizer for Alzheimer's Disease. It has been studied in healthy volunteers as well. The drug is in Phase 2 clinical development, though all five completed trials to date were Phase 1 studies.

Who makes PF-04447943?

PF-04447943 is being developed by Pfizer, Inc., which trades under the ticker PFE. The company has sponsored five clinical trials of the drug, all of which are now completed.

What phase is PF-04447943 in?

PF-04447943 is in Phase 2 clinical development for Alzheimer's Disease. However, all five completed trials listed for the drug were Phase 1 studies. It remains an investigational agent and is not FDA approved.

What clinical trials has PF-04447943 been in?

PF-04447943 has been studied in five completed trials, including NCT00832052 in healthy elderly participants, NCT00886093 examining food effects, NCT01097876 with donepezil, and NCT02785770 evaluating QTc interval effects. All were Phase 1 studies.

Is PF-04447943 the same as another drug?

PF-04447943 is the primary name used in clinical trial records. No alternative names have been associated with this compound in the available data.