A Dose Titration Study of CPC-201 in Patients With Dementia of Alzheimer's Type
Condition: Dementia of Alzheimer's Type
MeSH terms: Dementia; Alzheimer Disease
Intervention: Donepezil; Solifenacin
Intervention description: Donepezil dose increased at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) together with solifenacin.; Donepezil dose increased at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) together with solifenacin.
Intervention MeSH terms: Donepezil; Solifenacin Succinate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Enrollment: 28.0
Sex: All
Minimum age: 50 Years
Maximum age: 89 Years
Healthy volunteers: No

Summary:

      This is a Phase II, ascending dose study of CPC-201 in patients with dementia of Alzheimer's
      type to determine the optimal dose titration schedule.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed an Institutional Review Board (IRB) approved informed consent document

          2. Aged 50 - 89 years inclusive.

          3. Meeting the diagnosis of probable AD consistent with:

               -  Revised National Institute on Aging-Alzheimer's Disease Association (NIA-ADA)
                  criteria and

               -  Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria.

          4. Mild to severe severity (Mini-Mental Status Exam [MMSE] scores 7 - 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. Patients treated with donepezil 5 or 10 mg/day (given once daily) for at least 4 weeks
             just prior to Day1 for Population (group) 1 or;

          8. Patients never been treated with donepezil before (donepezil naïve) or who have not
             received any other AChEI for the past 6 months for Population (group) 2.

          9. Patients 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. Current unstable peptic ulcer disease, urinary or gastric retention; asthma or
             obstructive pulmonary disease.

          4. History or presence of bladder outflow obstruction, gastrointestinal obstructive
             disorder or reduced GI motility, or narrow-angle glaucoma.

          5. History or presence of gastrointestinal, hepatic, or renal disease, or other condition
             known to interfere with the absorption, distribution, metabolism or excretion of
             drugs.

          6. 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)

          7. History or presence of myasthenia.

          8. History or family history of Prolonged QT Syndrome.

          9. History of unexplained syncope or family history of unexplained syncope or sudden
             death.

         10. Myocardial infarction or hospitalization for congestive heart failure within 6 months.

         11. ECG findings of:

               -  Complete Left Bundle Branch Block;

               -  Ventricular pacing;

               -  2nd degree or 3rd degree AV block;

               -  Atrial fibrillation or atrial flutter;

               -  HR <45 or >100;

               -  PR >220 msec; or

               -  QTcF >450 msec in male, >470 msec in female

         12. Known hypersensitivity to donepezil, solifenacin or related drugs.

         13. History of drug significant allergy.

         14. History of substance abuse, known drug addiction, or positive test for drugs of abuse
             or alcohol.

         15. 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.

         16. Patients considered unlikely to co-operate in the study, and/or poor compliance
             anticipated by the investigator.

         17. Patients hospitalized within 4 weeks of screening.

         18. 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.

         19. Patients who have participated in another clinical trial with an investigational drug
             within previous 30 days.