Alzheimer's Disease
Conditions
Brief summary
This is a Phase II, Single-Blind, Placebo-Controlled, Sequential Treatment, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of CPC-201 in Patients with Alzheimer's Disease Type Dementia.
Interventions
DRUGCPC-201
Sponsors
Chase Pharmaceuticals Corporation, an affiliate of Allergan plc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Aged 50 - 79 years inclusive. * Meeting the diagnosis of probable Alzheimer's Disease * Of moderate severity (Mini-Mental Status Exam \[MMSE\] score 10 - 20 inclusive). * 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
* Women of child bearing potential. * History or presence of a seizure disorder. * History of 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. * History or presence of myasthenia. * Known hypersensitivity to donepezil, solifenacin or related drugs. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Donepezil Maximum Tolerated Dose (MTD) | 6 months | Number of participants who reached Donepezil Maximum Tolerated Dose of 40 mg/day (highest allowed per protocol) at the end of donepezil dose titration phase and at the end of the maintenance phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any TEAEs | 6 months | Number of subjects who experienced any treatment-emergent adverse events (TEAEs) at any time during the study. |
| Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Day 1 (baseline) to end of study | Donepezil Plasma Concentration pre-dose and 4 hour post-dose at Maximum Tolerated (MTD) or Maximum Allowable Dose, measured at baseline, at end of donepezil dose titration and at the end of maintenance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All subjects who received at least one dose of any study drug. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Donepezil Dose Escalation Phase | Adverse Event | 0 | 1 | 0 |
| Donepezil Dose Escalation Phase | Cardiac symptoms | 0 | 1 | 0 |
| Donepezil Dose Escalation Phase | No longer meeting eligibility criteria | 0 | 2 | 0 |
| Donepezil Dose Escalation Phase | Withdrawal by Subject | 0 | 1 | 0 |
| Donepezil Dose Maintenance Phase | Cardiac symptoms | 0 | 0 | 1 |
| Donepezil Dose Maintenance Phase | Withdrawal by Subject | 0 | 0 | 2 |
| Solifenacin Dose Escalation Phase | Cardiac symptoms | 1 | 0 | 0 |
| Solifenacin Dose Escalation Phase | No longer meeting eligibility criteria | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 73.1 Years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 41 |
| serious Total, serious adverse events | 8 / 41 |
Outcome results
Primary
Donepezil Maximum Tolerated Dose (MTD)
Number of participants who reached Donepezil Maximum Tolerated Dose of 40 mg/day (highest allowed per protocol) at the end of donepezil dose titration phase and at the end of the maintenance phase.
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 20 mg/day | 0 Participants |
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 30 mg/day | 1 Participants |
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 35 mg/day | 1 Participants |
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 15 mg/day | 0 Participants |
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 40 mg/day | 29 Participants |
| Donepezil Dose Escalation | Donepezil Maximum Tolerated Dose (MTD) | 25 mg/day | 2 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 40 mg/day | 28 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 15 mg/day | 0 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 20 mg/day | 0 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 25 mg/day | 2 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 35 mg/day | 1 Participants |
| Donepezil Dose Maintenance | Donepezil Maximum Tolerated Dose (MTD) | 30 mg/day | 2 Participants |
Secondary
Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose
Donepezil Plasma Concentration pre-dose and 4 hour post-dose at Maximum Tolerated (MTD) or Maximum Allowable Dose, measured at baseline, at end of donepezil dose titration and at the end of maintenance.
Time frame: Day 1 (baseline) to end of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil Dose Escalation | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration pre-dose (ng/mL) | 42.7 ng/mL | Standard Deviation 20.27 |
| Donepezil Dose Escalation | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration 4 hour post-dose (ng/mL) | 57.2 ng/mL | Standard Deviation 21.58 |
| Donepezil Dose Maintenance | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration pre-dose (ng/mL) | 184.2 ng/mL | Standard Deviation 65.95 |
| Donepezil Dose Maintenance | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration 4 hour post-dose (ng/mL) | 257.5 ng/mL | Standard Deviation 80.56 |
| Donepezil Dose Maintenance | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration pre-dose (ng/mL) | 188.1 ng/mL | Standard Deviation 64.21 |
| Donepezil Dose Maintenance | Donepezil Plasma Concentration at Maximum Tolerated (MTD) or Maximum Allowable Dose | Donepezil Concentration 4 hour post-dose (ng/mL) | 269.2 ng/mL | Standard Deviation 80.94 |
Secondary
Number of Subjects With Any TEAEs
Number of subjects who experienced any treatment-emergent adverse events (TEAEs) at any time during the study.
Time frame: 6 months
Population: All subjects those who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil Dose Escalation | Number of Subjects With Any TEAEs | Serious Adverse Events (SAEs) | 8 Participants |
| Donepezil Dose Escalation | Number of Subjects With Any TEAEs | Non-serious AEs | 34 Participants |
| Donepezil Dose Escalation | Number of Subjects With Any TEAEs | Deaths | 1 Participants |