Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil
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| ClinicalTrials.gov Identifier: NCT01712074 |
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Recruitment Status :
Terminated
(The study was terminated October 23, 2015 as pre-specified, interim analysis futility criteria were met. The termination was not due to safety concerns.)
First Posted : October 23, 2012
Results First Posted : March 20, 2017
Last Update Posted : March 20, 2017
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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Brief Summary:
This study will evaluate safety and efficacy of PF-05212377 in subjects with mild-to-moderate Alzheimer's Disease with existing neuropsychiatric symptoms on a stable dose of Donepezil. The 4-week run-in will minimize placebo effect. The 12-week treatment period is considered the minimum length necessary to reliably evaluate the effect PF-05212377 on cognition and and neuropsychiatric symptoms in this population. The 2-week washout will allow to monitor re-emergence of neuropsychiatric and cognitive symptoms.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alzheimer's Disease | Drug: PF-05212377 (SAM-760) Other: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 186 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy Of Pf-05212377 (Sam-760) In Subjects With Mild-to-moderate Alzheimer's Disease With Existing Neuropsychiatric Symptoms On A Stable Daily Dose Of Donepezil |
| Study Start Date : | November 2012 |
| Actual Primary Completion Date : | September 2015 |
| Actual Study Completion Date : | September 2015 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
MedlinePlus related topics:
Alzheimer's Disease
| Arm | Intervention/treatment |
|---|---|
| Experimental: 30 mg QD of PF-05212377 |
Drug: PF-05212377 (SAM-760)
30 mg QD of PF-05212377 (SAM-760) |
| Placebo Comparator: Placebo |
Other: Placebo
Placebo QD |
Primary Outcome Measures :
- Change From Baseline in ADAS-cog13 Total Score at Week 16 [ Time Frame: Baseline and Week 16 ]ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening.
Secondary Outcome Measures :
- Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5) [ Time Frame: Baseline and Week 16 ]The NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. The NPI total score (for 12 behavioral domains) is calculated as the product of frequency and severity for each domain, and ranges from 0 to 144. An increase in score indicates a worsening of symptoms.
Other Outcome Measures:
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation [ Time Frame: Week 4 to Week 18 ]Proportion of participants with TEAEs leading to discontinuation over the 12-week double blind treatment period and washout. Adverse events (AEs) occurring following start of treatment or increasing in severity were counted as treatment emergent
- Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period [ Time Frame: Week 4 to Week 16 ]
Proportion (%) of participants with laboratory abnormalities (without regard to baseline abnormalities) of potential clinical concern over the 12-week double blind treatment period.
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (only at screening or needed: urine drug screen, thyroid panel, Vitamin B12, methylmalonic acid, folate and Hemoglobin A1).
- Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
- Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
- Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).
- Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]Proportion (%) of participants with PR Interval abnormalities meeting categorical criteria over the 12 week double blind treatment period. The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline PR absolute value>=300 msec , a PR increase of >=25% (for participants with a baseline value>=200 msec), or with an increase >=50% (for participants with a baseline value<200 msec) were counted.
- Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
- Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
- Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.
- Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]Proportion (%) of participants with QRS Complex abnormalities meeting categorical criteria over the 12 week double blind treatment period. The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline QRS complex absolute value>=100 msec , a QRS complex increase of >=25% (for participants with a baseline value>=100 msec), or with an increase >=50% (for participants with a baseline value<100 msec) were counted.
- Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
- Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
- Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
- Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]
Proportion (%) of participants with QTcF Interval abnormalities meeting categorical criteria over the 12-week double blind treatment period. The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.
Participants with a post-baseline QTcF absolute value of 450 - <480, 480 - <500, or >=500 mec, or with a post-baseline QTcF increase of 30 - <60 or >=60 msec were counted.
- Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]The BP changes from baseline at Week 6 (Visit 3) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
- Pulse Rate Changes From Baseline - Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]The pulse rate changes from baseline at Week 6 (Visit 3) including supine pulse rate, and standing pulse rate.
- BP Changes From Baseline - Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]The BP changes from baseline at Week 10 (Visit 4) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
- Pulse Rate Changes From Baseline - Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]The pulse rate changes from baseline at Week 10 (Visit 4) including supine pulse rate, and standing pulse rate.
- BP Changes From Baseline - Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]The BP changes from baseline at Week 16/Early Termination (Visit 5) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.
- Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]The pulse rate changes from baseline at Week 16/Early Termination (Visit 5) including supine pulse rate, and standing pulse rate.
- Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]Proportion (%) of participants with vital signs abnormalities (absolute and change from baseline) meeting categorical criteria over the 12-week double blind treatment period were counted. Vital signs data included blood pressure (BP) and pulse rate.
- Participants in Each Category of C-CASA Mapped From the C-SSRS Responses [ Time Frame: From Screening to Week 18/Early Termination ]
Participants in each category of the Columbia Classification Algorithm of Suicide Assessment (C-CASA) mapped from the Columbia-Suicide Severity Rating Scale (C-SSRS) responses were reported.
C-CASA Event Code: <1> Completed suicide; <2> Suicide attempt; <3> Preparatory acts towards imminent suicidal behavior; <4> Suicidal Ideation; <7> Self-injurious behavior, no suicidal intent.
The suicidality assessments were performed at Screening, Week 0 (Visit 1), Week 4 (Visit 2), Week 6, (Visit 3), Week 10 (Visit 4), Week 16 (Visit 5), and Week 18 (Visit 6).
Only participants falling any category of C-CASA events were listed below.
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| Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Clinical diagnosis of probable AD with supportive brain imaging documentation
- Have existing neuropsychiatric symptoms as defined by a score equal or greater than 10 on the NPI at screening, arising from item scores equal or greater than 2 (frequency X severity) on at least 2 domains.
- Has been on donepezil (stable dose of 5 mg or 10 mg) for at least four months, with no intent to change such for the duration of the study.
Exclusion Criteria:
- Demonstrate extreme agitation, physical aggression or violence to themselves, their caregiver, or others, and/or an inability to complete the ADAS-cog assessment at Screening.
- Have major structural brain disease other than Alzheimer's Disease
- Other severe acute or chronical medical or psychiatric condition or laboratory abnormality
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01712074
Locations
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Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT01712074 |
| Other Study ID Numbers: |
B2081011 2014-000830-42 ( EudraCT Number ) |
| First Posted: | October 23, 2012 Key Record Dates |
| Results First Posted: | March 20, 2017 |
| Last Update Posted: | March 20, 2017 |
| Last Verified: | January 2017 |
Keywords provided by Pfizer:
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Randomized Double Blind Safety and Efficacy |
Additional relevant MeSH terms:
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Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |