A Dose Titration Study of CPC-201 in Patients With Dementia of Alzheimer's Type (CPC-12)

A Phase II, Dose Titration Study of CPC-201 in Patients With Dementia of Alzheimer's Type

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.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

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. The study involves a step wise cohort design in two different patient populations: Group 1 will comprise of patients who have been treated with low dose of CPC-201(5 or 10 mg/day) (given once daily) for at least 4 weeks just prior to Day1. Group 2 will consist of patients who have never been treated with CPC-201 before or who have not received any other AChEI for the past 6 months.

In this study, CPC-201 dose will be increased at weekly intervals, in accordance with the schedules given below, to its first intolerable dose (FID) or maximum allowed dose (MAD) of 60 mg/day (40mg/day for Cohort 3c) together with solifenacin 15 mg/day.

Cohort 1 1st week: 20mg 2nd week: 30mg 3rd week: 40mg 4th week: 50mg 5th week: 60mg Cohort 2* 1st week: 20mg 2nd week: 40mg 3rd week: 60mg Cohort 1b 1st - 2nd week: 10mg 3rd week: 20mg 4th week: 30mg 5th week: 40mg 6th week: 50mg 7th week: 60mg Cohort 3c* 1st week: 10mg 2nd week: 15mg 3rd week: 20mg 4th week: 25mg 5th week: 30mg 6th week: 35mg 7th week: 40mg

*: The dose titration schedule of Cohort 2 and 3 may be altered based on Cohort 1 result.

Patients will be enrolled in Cohort 2 only when patients enrolled in Cohort 1 have safely completed titration. Similary, patients will be enrolled in Cohort 3, only when patients enrolled in Cohort 2 have safely completed titration.

Patients reaching their FID or having completed one week treatment with donepezil 40mg/day, have two options.

Option 1: Patient will be allowed to immediately enter a long term extension at their Maximum tolerated dose (MTD) or MAD.

Option 2: Patients may choose not to enter the long term extension, in which case the Investigator will decide whether the patient should discontinue high dose of donepezil without down-titration, or whether donepezil should be downtitrated to their own standard of donepezil dose.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Deerfield Beach, Florida, United States, 33064
        • Quantum Laboratories
      • Miami, Florida, United States, 33137
        • Miami Jewish Health Systems
      • West Palm Beach, Florida, United States, 33407
        • Premiere Research Institute
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • PMG Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years to 87 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
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 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.
Experimental: Cohort 2
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 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.
Experimental: Cohort 1b
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 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.
Experimental: Cohort 3c
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Reached the Maximum Allowed Dose (MAD) in Their Respective Cohort
Time Frame: 1-7 weeks
Of the four cohorts with different dosing schedules for CPC-201, the cohort with the greatest proportion of participants to reach the donepezil MAD was determined to be the optimal administration regimen.
1-7 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With TEAEs Leading to Study Drug Discontinuation
Time Frame: 1-7 weeks
Number of subjects who experienced any treatment-emergent adverse events (TEAEs) leading to study drug discontinuation
1-7 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Lynn James, Allergan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2015

Primary Completion (Actual)

September 28, 2017

Study Completion (Actual)

September 28, 2017

Study Registration Dates

First Submitted

August 27, 2015

First Submitted That Met QC Criteria

September 11, 2015

First Posted (Estimate)

September 15, 2015

Study Record Updates

Last Update Posted (Actual)

March 5, 2019

Last Update Submitted That Met QC Criteria

February 12, 2019

Last Verified

February 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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