CPC-201 Alzheimer's Disease Type Dementia: PET Study

August 8, 2017 updated by: Chase Pharmaceuticals Corporation, an affiliate of Allergan plc

Phase II, Modified Single-Blind, Sequential Treatment, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Cerebral Efficacy of CPC-201 in Patients With Alzheimer's Disease Type Dementia: PET Study

The purpose of this study is to compare the effect of low and high dose CPC-201 on brain function including cerebral acetylcholinesterase (AChE) activity measured by positron emission tomography (PET).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • Michigan
      • West Bloomfield Township, Michigan, United States, 48322
        • Henry Ford Health System--West Bloomfield Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 79 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 indicating that they understand the purpose of and procedures required by the study protocol and are willing to participate in the study and comply with all its procedures and restrictions. Informed consent must be obtained from the patient and/or a designated representative prior to initiating screening procedures to evaluate their eligibility for the study.
  2. Aged 50 - 79 years inclusive.

  3. Meet the diagnosis of probable AD consistent with:

    • Revised National Institute on Aging-Alzheimer's Association (NIA-ADA) criteria and
    • Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria.
  4. Of mild to moderate severity: Mini-Mental Status Exam (MMSE) score 10 - 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. Treated with donepezil 10 mg/day (given once daily) for at least 4 weeks just prior to study entry and to have safely tolerated, as judged clinically by the investigator.
  8. 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:

  1. Women of child bearing potential.
  2. History or presence of a seizure disorder.
  3. History of uncontrolled peptic ulcer disease, urinary or gastric retention; asthma or obstructive pulmonary disease.
  4. History or presence of uncontrolled bladder outflow obstruction, gastrointestinal obstructive disorder or reduced gastrointestinal motility, or narrow-angle glaucoma.

  5. 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)
  6. History or presence of myasthenia.
  7. History of Prolonged QT Syndrome.
  8. History of unexplained syncope.
  9. Myocardial infarction or hospitalization for congestive heart failure within 6 months.
  10. Patients has implanted cardiac pacemaker, implantable cardiac defibrillator (ICD), or metallic objects located in the eye, neck, ear, brain or blood vessel walls.

  11. ECG findings of:

    • Complete Left Bundle Branch block;
    • Ventricular pacing;
    • 2nd degree or 3rd degree AV block;
    • Atrial fibrillation or atrial flutter;
    • Heart rate <45 or >100;
    • PR >220 msec; or
    • QTcF >450 msec in male, >470 msec in female

  12. 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.

  13. Claustrophobia
  14. Patients considered unlikely to cooperate in the study, and/or poor compliance anticipated by the investigator.
  15. 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.
  16. 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CPC-201
combination of solifenacin and high doses of donepezil
Drug: CPC-201
solifenacin and donepezil
Other: Positron emission tomography (PET)
measure activity of cerebral acetylcholinesterase

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Donepezil Maximum tolerated dose (MTD) change on imaging
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chase Pharmaceuticals Corporation, an affiliate of Allergan plc

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 (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 30, 2016

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2017

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CPC-001-15

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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