Study to test whether PF-05212377 is safe and improves symptoms in patients with Alzheimer's disease with existing neuropsychiatric symptoms.

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2014-000830-42-ES
• Date of registration: 22/05/2014
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, 10017
• Public title: Study to test whether PF-05212377 is safe and improves symptoms in patients with Alzheimer's disease with existing neuropsychiatric symptoms.
• Scientific 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. - SAM-760
• Date of first enrolment: 23/10/2014
• Target sample size: 290
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000830-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Canada, Chile, France, Germany, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member
of the investigator?s study team before subjects are included in the study.

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1. Evidence of a personally signed and dated informed consent document indicating that the subject (and/or a legal representative) has been informed of all pertinent aspects of the study. Subject caregiver must also consent to participate in the study. If the subject lacks sufficient decision-making capacity, in the opinion of the investigator (with appropriate documentation of such), a mentally-competent legal representative must provide informed consent on his/her behalf, and the subject must provide verbal or written assent.

2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

3. Men and women of non-childbearing potential ?60 years of age.
Since women are over the age of 60, they are considered post-menopausal and therefore of non-child bearing potential (WONCBP).
If male, either a) of reproductive potential and compliant in using adequate birth control or are b) not of reproductive potential. Surgical sterilization must be documented. Adequate birth control for males is defined as a condom and spermicidal gel or foam, or abstinence, defined as no intercourse with any female of child bearing potential throughout the duration of the study, which is any female not meeting above definition for non-child bearing potential.

4. Diagnosis of probable AD (with appropriate documentation of supporting data) according to the following criteria:
a. Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision (DSM-IV-TR);
b. National Institute of Neurological and Communicative Disorders and Stroke ? Alzheimer?s Disease and Related Disorder Association?s Criteria
(NINCDS-ADRDA) for probable AD;
c. MMSE score between 10 and 24, inclusive, at Screen and Visit 1;
d. Modified Hachinski Ischemic Score ? 4.

5. Have existing neuropsychiatric symptoms as defined by a score ?10 on the NPI at screening, arising from item scores of ?2 (frequency X severity) on at least 2 domains.

6. Have had brain imaging such as magnetic resonance imaging (MRI) or CT scan within 12 months of screening consistent with a diagnosis of probable AD without any other clinically significant co-morbid pathologies found. If there has been a
significant change in clinical status suggestive of stroke or other possible neurological disease with onset between the time of the last MRI or CT (if applicable) and the Screening evaluation, an MRI or CT scan may be obtained at screening if considered
appropriate by the investigator.

7. Have been taking donepezil at a stable dose of 5 mg or 10 mg at a stable formulation, for at least four months prior to Visit 1, with no intent to change such for the duration of the study (unless medically indicated and unexpected). Subjects not currently on
donepezil can be started on donepezil and stabilized for 4 months prior to Visit 1. The Sponsor may provide financial support for background donepezil therapy, on request, on a case by case basis.

8. If taking antidepressants, must be on a stable dose and regimen for at least 30 days prior to the Screening visit and for the duration of the study.

9. Have at least eight years of prior education and should have previously (in pre-AD condition
Exclusion criteria:
1. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Demonstrate extreme agitation, physical aggression or violence to themselves, their caregiver, or others, or who have a severity of behavioral disturbance at screening that would compromise the assessment of cognition, based on the opinion of the
investigator and/or an inability to complete the ADAS-cog assessment at Screening.
3. Have major structural brain disease (eg, ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region [eg, thalamus, hippocampus], or a degree of white matter disease sufficient to call into question the diagnosis of primary AD vs. vascular dementia).
4. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study restuls and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

a. Any physical disability that would prevent completion of study procedures or assessments (eg, blindness or significant visual impairment, deafness or significant hearing impairment not corrected by hearing aids, non AD related speech impairment).

b. A diagnosis of unstable diabetes mellitus defined as:
? requiring insulin treatment, except that once daily administration of basal long-acting insulin is acceptable if stable for at least 30 days;
? HbA1C >8% or fasting serum glucose value >140 mg/dl at Screening (may be repeated once for confirmation).

c. A history of cancer within five years of enrollment with the exception of non-melanoma skin cancers or prostate cancer that has been stable for at least six
months or American Joint Committee on Cancer (AJCC) Grade 0 or Grade 1 cancers that have a remote probability of recurrence, in the opinion of the
investigator, in consultation with the Sponsor;

d. The following cardiovascular parameters:
? Hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or bradycardia with heart rate less than 50 beats per minute during Screening (based on heart rate value from ECG determined by central ECG vendor) or on more than one occasion within three months prior to enrollment (out of range values may be repeated once for confirmation);
? Uncontrolled hypertension (documented my medical records) as indicated by a resting systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg during Screening or on more than one occasion within three months prior to Screening (out of range values may be repeated once for confirmation);
? A corrected QT interval by the Fridericia correction formula (QTcF) of greater than 470 milliseconds (msec) based on the ECG report from the central ECG vendor or any other clinically significant abnormality found on an ECG during Screening (may be repeated once);
? Active cardiovascular disease including any of the following: unstable angina, decompensated congestive heart failure, clinically relevant arrhythmias, recent myocardial infarction, or valve abnormalities. NOTE: A history of these conditions is acceptable, if stable under medical management. Subjects with pacemakers, cardiac stents, and internal defibrillators acceptable if subject

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Mild-to-Moderate Alzheimer's Disease with extising Nueropsychiatric Symptoms
MedDRA version: 17.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852

Intervention(s)

Product Code: PF-05212377 (SAM-760)
Pharmaceutical Form: Capsule
INN or Proposed INN: PF-05212377
Other descriptive name: SAM-760
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the change from baseline (Visit 2, Week 4) to 12 weeks after the start of double-blind study medication on the ADAS-cog13 total score (Visit 5, Week 16).

Main Objective: To evaluate the efficacy of PF-05212377 (SAM-760) 30 mg QD as compared to placebo on the primary measure of cognition and memory, the Alzheimer?s Disease Assessment Scale ? cognitive subscale (13 item; ADAS-cog13) 12 weeks after start of double-blind study medication.

Timepoint(s) of evaluation of this end point: Week 16

Secondary Objective: To evaluate the efficacy of PF-05212377 (SAM-760) 30 mg QD as compared to placebo on a broad measure of behavior, the Neuropsychiatric Inventory (12 item) (NPI) at 12 weeks after start of double-blind study medication.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoint is the change from baseline (Visit 2, Week 4) to 12 weeks after the start of double-blind study medication on the NPI total score (Visit 5, Week 16).

Timepoint(s) of evaluation of this end point: Week 16

Secondary ID(s)

B2081011

Source(s) of Monetary Support

Pfizer Inc