Safety and Efficacy Study of CEP-1347 in the Treatment of Parkinson's Disease

Study Overview
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Brief Summary
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The purpose of this study is to establish safety for CEP-1347 and to determine an efficacious dose in the treatment of Parkinson's disease.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Efficacy and Safety of CEP-1347 in Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: CEP-1347 10mg
* Drug: CEP1347 25mg
* Drug: CEP-1347 50mg
* Other: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be included in the study if all of the following criteria are met: Willing and able to give informed consent Age 30 years or older at time of diagnosis of Parkinson's disease Have idiopathic Parkinson's disease with at least 2 cardinal signs of disease: resting tremor, bradykinesia, or rigidity Modified Hoehn and Yahr stage less than or equal to 2.5 Must have had screening procedures for cancer appropriate for the patient's age and gender, within the last 12 months; or be willing to obtain such screening before randomization Women: are not breastfeeding Women: nonchildbearing potential (ie, postmenopausal or surgically sterile) or must use a medically accepted contraceptive regimen for at least 60 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug. Women must be given a pregnancy test unless they are at least 2 years postmenopausal or surgically sterile. Exclusion Criteria: Patients will be excluded from participating in this study if 1 or more of the following criteria are met: Have atypical Parkinsonism due to drugs, metabolic disorders, encephalitis, or other neurodegenerative diseases Have confirmed diagnosis of Parkinson's disease for more than 5 years Have a tremor score of 3 or more in any body part Have any other known medical or psychiatric condition that may compromise participation in the study Have a history of prior malignancy (excluding basal or squamous cell cancer of the skin) within the previous 5 years Have an unresolved abnormal cancer screening test result before randomization Have greater than trace amounts of glycosuria at screening, except for known diabetic patients Have estimated creatinine clearance less than 50 mL/min Have liver function tests (LFT) greater than 3 times the upper limit of normal (ULN) Have any other clinically significant ECG or laboratory finding Have any history of malignant melanoma Have history of seizures (except febrile) or posttraumatic epilepsy Have Mini-Mental State Exam (MMSE) score ≤ 26 Have taken another investigational drug within 60 days before the baseline visit Have received prior treatment with CEP-1347 Have received treatment with agents with potentially confounding anti-Parkinson's disease effects, with specified substrates for CYP3A4/5, or with inhibitors of CYP3A4/5 Received treatment within 6 months before the baseline visit with agents that may induce Parkinson's disease Are expected, within the next 3 months, to reach a level of disability sufficient to require dopaminergic therapy Have BECK depression score ≥ 15 Have known or suspected sensitivity to the investigational study drugs, including B-CIT

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CEP-1347 10mg<br>CEP-1347 was administered at a dosage of 10mg twice daily (bid); capsule strengths were 5, 12.5, and 25 mg. Each patient took 2 capsules at each dosing time, approximately 12 hours apart, within 30 minutes after the morning and evening meals) for a total of 4 capsules per day.Patients were randomly assigned to CEP-1347 or placebo treatment in a 1:1:1:1 ratio. A blocked randomization scheme was used to ensure approximately equal numbers of patients in each of the 4 treatment groups at each center. | Drug: CEP-1347 10mg<br>* CEP-1347 10mg, a K252a derivative, retains neuroprotective properties<br>|
| Experimental: CEP-1347 25mg<br>CEP-1347 was administered at a dosage of 25mg twice daily (bid); capsule strengths were 5, 12.5, and 25 mg. Each patient took 2 capsules at each dosing time, approximately 12 hours apart, within 30 minutes after the morning and evening meals) for a total of 4 capsules per day.Patients were randomly assigned to CEP-1347 or placebo treatment in a 1:1:1:1 ratio. A blocked randomization scheme was used to ensure approximately equal numbers of patients in each of the 4 treatment groups at each center. | Drug: CEP1347 25mg<br>* CEP1347 25mg, a K252a derivative, retains neuroprotective properties<br>|
| Experimental: CEP-1347 50mg<br>CEP-1347 was administered at a dosage of 50mg twice daily (bid); capsule strengths were 5, 12.5, and 25 mg. Each patient took 2 capsules at each dosing time, approximately 12 hours apart, within 30 minutes after the morning and evening meals) for a total of 4 capsules per day.Patients were randomly assigned to CEP-1347 or placebo treatment in a 1:1:1:1 ratio. A blocked randomization scheme was used to ensure approximately equal numbers of patients in each of the 4 treatment groups at each center. | Drug: CEP-1347 50mg<br>* CEP-1347 50mg, a K252a derivative, retains neuroprotective properties<br>|
| Placebo Comparator: Placebo<br>Placebo capsules matching the CEP-1347 capsules were administered in the same manner. | Other: Placebo Comparator<br>* Placebo capsules matching the CEP-1347 capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with disability using United Parkinson's Disease Rating Scale (UPDRS) | Number of participants with disability sufficient to require dopaminergic therapy was assessed according to the United Parkinson's Disease Rating Scale (UPDRS) Parts I and II are historical data and are designed to rate mentation, behavior and mood; Part III is done as a motor examination at the time of a visit. The UPDRS measures patient status on a scale 0, which is normal or none, to 4, which is severe or the worst scenario. | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to 22 months in ([123I]β-CIT) Uptake Participants | The effect of CEP-1347 on dopaminergic transporter density using 2β-carboxymethoxy-3β-(4-iodophenyl) tropane ([123I]β-CIT) single-photon emission computed tomography (SPECT) imaging | Change from Baseline to 22 months | 
| Safety and Tolerability as assessed by the number of participants experiencing adverse events | Safety was assessed by adverse events (including deaths, serious adverse events, and withdrawals due to adverse events.) | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Idiopathic Parkinson's disease, Idiopathic Parkinson disease, Parkinson's disease, idiopathic