CPC-201 Alzheimer's Disease Type Dementia: PET Study

Patients will continue on the 10 mg/day dose of donepezil with the addition of 15 mg/day of
solifenacin at least for a week, donepezil will be titrated from 10 to 50 mg/day (maximum
allowed dose; MAD) or each patient's MTD with increments of 5 or 10 mg weekly or bi-weekly as
medically appropriate. When the MTD or MAD of donepezil co-administered with solifenacin 15
mg/day as CPC-201 has been reached, treatment will be stably maintained, as tolerated, for 3
months.

Patients successfully completing this protocol will have the option of continuing in an open
extension of their CPC-201 treatment (separate protocol) or returned to their pre-admission
therapeutic regimen and discharged from the study.

On the days of study drug dose increase, patients will be evaluated at a clinic as an
out-patient.

This is a sequential study conducted in 6 phases in AD patients who had previously been
receiving donepezil at a dose of 10 mg/day:

1. Screening

2. Baseline assessment

3. Solifenacin introduction at a dose of 15 mg/day (given with continued donepezil 10
mg/day as CPC-201);

4. Donepezil dose escalation to each subject's MTD or 50 mg/day (MAD), given in combination
with solifenacin 15 mg/day as CPC-201;

5. Donepezil maintenance at its MTD (or MAD) combined with solifenacin 15 mg/day as CPC-201
for 3 months;

6. Protocol exit (after resumption of pre-study treatment regimen and successful completion
of a one month post-study safety check) or optional entry into a 6 month extension
phase.

Baseline assessment (during solifenacin introduction): Upon successful completion of a
screening evaluation and entry into this study, participants will continue to receive 10 mg
donepezil and receive neuropsychological evaluations at the clinic together with a 11C-PMP
PET scan and associated MRI studies of the brain in accordance with the University of
Michigan.

Solifenacin introduction: After the one week baseline assessment period, solifenacin
treatment will be initiated at 15 mg/day for at least one week while patients continue to
receive donepezil at a dose of 10 mg/day. Those who do not tolerate solifenacin will be
withdrawn from the study and replaced.

Donepezil escalation: During this phase, while continuing to receive 15 mg/day of
solifenacin, the dose of donepezil will be gradually increased at weekly or bi-weekly with
increments of 5 or 10 mg as tolerated. The dose of donepezil will be increased until the
first intolerable dose (FID) is reached or a dose of 50 mg/day is attained, whichever comes
first. Once patients reach their FID, their MTD will be defined as their immediately
preceding, tolerated dose. During dose titration, investigators may extend the same donepezil
dose for additional days or temporarily (or permanently) reduce it as medically indicated. On
the days of donepezil dose increase, patients will remain in the clinic for at least 5 hours
after study drug administration or until signs and symptoms of medically significant adverse
effects abate.

Donepezil dose maintenance: During this phase, patients will continue treatment with
donepezil (at MTD) and solifenacin (15 mg/day) for 3 months (± 2 weeks). All will be followed
by weekly telephone interviews and monthly clinic visits to assess safety and tolerability.
If intolerable adverse events (AEs) develop, the daily dose of donepezil will be
down-titrated, and the patient will continue treatment on their new MTD for an additional 2
weeks or up to completion of the maintenance phase, whichever comes last. Patients who
continue to experience intolerable AEs after several down-titrations will be withdrawn from
the study.

End of study testing at the end of donepezil dose maintenance: After completion of 3-months
(± 2 weeks) treatment with donepezil (at MTD) and solifenacin (15 mg/day), study participants
will receive a repeat of their clinical examination, routine laboratory safety tests and PET
associated studies.

Patients successfully completing this protocol will then have the option of continuing in an
open extension of their CPC-201 treatment (separate protocol) or to be returned to their
pre-admission therapeutic regimen and discharged from the study.

Study Exit: Upon termination of this study, subjects will return to their original daily
donepezil dose. Investigator will decide whether the patient should discontinue high dose of
donepezil without down-titration, or whether donepezil should be down-titrated to their
prestudy donepezil dose. Whatever the decision, the patient will ordinarily be treated at
least an additional 7 days with solifenacin 15 mg/day.

Inclusion Criteria:

1. Signed an Institutional Review Board (IRB) approved informed consent document
indicating that they understand the purpose of and procedures required by the study
protocol and are willing to participate in the study and comply with all its
procedures and restrictions. Informed consent must be obtained from the patient and/or
a designated representative prior to initiating screening procedures to evaluate their
eligibility for the study.

2. Aged 50 - 79 years inclusive.

3. Meet the diagnosis of probable AD consistent with:

- Revised National Institute on Aging-Alzheimer's Association (NIA-ADA) criteria
and

- Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria.

4. Of mild to moderate severity: Mini-Mental Status Exam (MMSE) score 10 - 24 inclusive.

5. Rosen-Modified Hachinski Ischemia Score of ≤4.

6. Have a suitable caregiver to supervise the at-home administration of study drugs and
observe for AEs.

7. Treated with donepezil 10 mg/day (given once daily) for at least 4 weeks just prior to
study entry and to have safely tolerated, as judged clinically by the investigator.

8. Patients must be in generally good health as indicated by their medical history and
physical examination, vital signs, electrocardiogram (ECG), and standard laboratory
tests.

Exclusion Criteria:

1. Women of child bearing potential.

2. History or presence of a seizure disorder.

3. History of uncontrolled peptic ulcer disease, urinary or gastric retention; asthma or
obstructive pulmonary disease.

4. History or presence of uncontrolled bladder outflow obstruction, gastrointestinal
obstructive disorder or reduced gastrointestinal motility, or narrow-angle glaucoma.

5. Renal and hepatic dysfunction with:

- Total Bilirubin: >1.5 x UNL

- AST: >2.5 x UNL

- ALT: >2.5 x UNL

- Serum Creatinine: >1.5 x UNL

- Creatinine Clearance: <30 mL/min (calculated by Cockcroft and Gault equation)

6. History or presence of myasthenia.

7. History of Prolonged QT Syndrome.

8. History of unexplained syncope.

9. Myocardial infarction or hospitalization for congestive heart failure within 6 months.

10. Patients has implanted cardiac pacemaker, implantable cardiac defibrillator (ICD), or
metallic objects located in the eye, neck, ear, brain or blood vessel walls.

11. ECG findings of:

- Complete Left Bundle Branch block;

- Ventricular pacing;

- 2nd degree or 3rd degree AV block;

- Atrial fibrillation or atrial flutter;

- Heart rate <45 or >100;

- PR >220 msec; or

- QTcF >450 msec in male, >470 msec in female

12. Patients treated with the following medications within 8 weeks of screening

- AChEIs (other than donepezil),

- Peripherally acting anticholinergics (such as drugs for the treatment of
overactive bladder disorder),

- Psychoactive medications (including antipsychotics, antidepressants, anxiolytics
or sedative hypnotics) having significant anticholinergic effects and/or believed
to affect cognitive function.

Other medications are acceptable, at the investigators discretion, if dosage is held
stable for at least 4 weeks prior to screening and throughout the study.

13. Claustrophobia

14. Patients considered unlikely to cooperate in the study, and/or poor compliance
anticipated by the investigator.

15. Any other clinically relevant acute or chronic diseases which could interfere with
patients' safety during the trial, or expose them to undue risk, or which could
interfere with study objectives.

16. Patients who have participated in another clinical trial with an investigational drug
within previous 30 days.