A Efficacy, Safety and Pharmacokinetic Study of XP21279 and Sinemet® in Parkinson's Disease Subjects

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy and safety of XP21279/Carbidopa in comparison to Sinemet as well as evaluate the pharmacokinetics (PK) of levodopa after administration of XP21279/Carbidopa and Sinemet and to explore exposure-response relationships in a subset of subjects.

Official Title
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A Phase 2 Efficacy, Safety and Pharmacokinetic Study of XP21279 BL2 and Sinemet® in Parkinson's Disease Subjects With Motor Fluctuations

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: XP21279 and carbidopa (experimental)
* Drug: Sinemet (comparator)
* Drug: Placebo for XP21279 and carbidopa
* Drug: Placebo for Sinemet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have predictable motor fluctuations of the wearing off type, defined by meeting the following criteria based on the on/off diaries recorded over 3 days in the Screening Period: Wearing-off in at least half (50%) of inter-dose intervals between the first and the last daily doses averaged over the 3 diary days, and An average daily off time of 2 hours after the first on of the day through awake time up to midnight. Subjects must be on one of the following stable QID or 5 times daily regimens for at least 4 weeks prior to Screening: Sinemet® or carbidopa-levodopa, with a total daily dose ranging from 400 mg to 1000 mg of levodopa Exclusion Criteria: History, signs, or symptoms suggesting the diagnosis of secondary or atypical Parkinsonism. Subject has moderately or severely disabling dyskinesias for greater than 25% of the waking day Subjects who have significant neurological symptoms not accounted for by Parkinson's disease Subjects who are taking Sinemet® CR, Parcopa®, concomitant COMT inhibitors (i.e., entacapone or tolcapone), Stalevo®, or benserazide containing levodopa preparations Madopar® or Prolopa®.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br>Subjects will receive XP21279 and carbidopa, Sinemet, placebo for XP21279 and carbidopa, placebo for Sinemet in a randomized sequence. | Drug: XP21279 and carbidopa (experimental)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed XP21279 and Carbidopa<br>Drug: Sinemet (comparator)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed Sinemet.<br>Drug: Placebo for XP21279 and carbidopa<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for XP21279 and carbidopa<br>Drug: Placebo for Sinemet<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for Sinemet<br>|
| Experimental: Treatment sequence 2<br>Subjects will receive XP21279 and carbidopa, Sinemet, placebo for XP21279 and carbidopa, placebo for Sinemet in a randomized sequence. | Drug: XP21279 and carbidopa (experimental)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed XP21279 and Carbidopa<br>Drug: Sinemet (comparator)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed Sinemet.<br>Drug: Placebo for XP21279 and carbidopa<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for XP21279 and carbidopa<br>Drug: Placebo for Sinemet<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for Sinemet<br>|
| Experimental: Treatment sequence 3<br>Subjects will receive XP21279 and carbidopa, Sinemet, placebo for XP21279 and carbidopa, placebo for Sinemet in a randomized sequence. | Drug: XP21279 and carbidopa (experimental)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed XP21279 and Carbidopa<br>Drug: Sinemet (comparator)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed Sinemet.<br>Drug: Placebo for XP21279 and carbidopa<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for XP21279 and carbidopa<br>Drug: Placebo for Sinemet<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for Sinemet<br>|
| Experimental: Treatment sequence 4<br>Subjects will receive XP21279 and carbidopa, Sinemet, placebo for XP21279 and carbidopa, placebo for Sinemet in a randomized sequence. | Drug: XP21279 and carbidopa (experimental)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed XP21279 and Carbidopa<br>Drug: Sinemet (comparator)<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed Sinemet.<br>Drug: Placebo for XP21279 and carbidopa<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for XP21279 and carbidopa<br>Drug: Placebo for Sinemet<br>* Eligible subjects entering the study will be randomized into 1 of 4 sequences where they will be dosed placebo for Sinemet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mean daily off time at end of double-blind maintenance treatment periods. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders (much improved or very much improved) on Investigator-rated and patient-rated CGI-I at end of double-blind Maintenance Treatment periods |  | 2 weeks |