A Dose Titration Study of CPC-201 in Patients With Dementia of Alzheimer's Type (CPC-12)
Dementia of Alzheimer's Type
About this trial
This is an interventional treatment trial for Dementia of Alzheimer's Type
Eligibility Criteria
Inclusion Criteria:
- Signed an Institutional Review Board (IRB) approved informed consent document
- Aged 50 - 89 years inclusive.
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.
- Mild to severe severity (Mini-Mental Status Exam [MMSE] scores 7 - 24 inclusive).
- Rosen-Modified Hachinski Ischemia Score of ≤4.
- Have a suitable caregiver to supervise the at-home administration of study drugs and observe for AEs.
- 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;
- 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.
- Patients in generally good health as indicated by their medical history and physical examination, vital signs, electrocardiogram (ECG), and standard laboratory tests.
Exclusion Criteria:
- Women of child bearing potential.
- History or presence of a seizure disorder.
- Current unstable peptic ulcer disease, urinary or gastric retention; asthma or obstructive pulmonary disease.
- History or presence of bladder outflow obstruction, gastrointestinal obstructive disorder or reduced GI motility, or narrow-angle glaucoma.
- History or presence of gastrointestinal, hepatic, or renal disease, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
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)
- History or presence of myasthenia.
- History or family history of Prolonged QT Syndrome.
- History of unexplained syncope or family history of unexplained syncope or sudden death.
- Myocardial infarction or hospitalization for congestive heart failure within 6 months.
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
- Known hypersensitivity to donepezil, solifenacin or related drugs.
- History of drug significant allergy.
- History of substance abuse, known drug addiction, or positive test for drugs of abuse or alcohol.
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.
- Patients considered unlikely to co-operate in the study, and/or poor compliance anticipated by the investigator.
- Patients hospitalized within 4 weeks of screening.
- 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.
- Patients who have participated in another clinical trial with an investigational drug within previous 30 days.
Sites / Locations
- Quantum Laboratories
- Miami Jewish Health Systems
- Premiere Research Institute
- PMG Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Cohort 1
Cohort 2
Cohort 1b
Cohort 3c
Donepezil 20mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
Donepezil 20mg/day upward dose titration of 20mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
Donepezil 10mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
Donepezil 10mg/day upward dose titration of 5mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 40mg/day with solifenacin 15mg/day.