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 Those who do not tolerate solifenacin will be withdrawn from the study and replaced.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.