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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: XP21279 and carbidopa (experimental); Drug: Sinemet (comparator); Drug: Placebo for XP21279 and carbidopa; Drug: Placebo for Sinemet

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • XenoPort Clinical Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • XenoPort Clinical Site
  • California
    • Long Beach, California, United States, 90806
      • XenoPort Clinical Site
    • Sunnyvale, California, United States, 94085
      • XenoPort Clinical Site
  • Florida
    • Naples, Florida, United States, 34102
      • XenoPort Clinical Site
    • Tampa, Florida, United States, 33606
      • XenoPort Clinical Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • XenoPort Clinical Site
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • XenoPort Clinical Site
    • West Bloomfield, Michigan, United States, 48322-3013
      • XenoPort Clinical Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • XenoPort Clinical Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
      • XenoPort Clinical Site
  • Texas
    • Houston, Texas, United States, 77030
      • XenoPort Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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:

1. History, signs, or symptoms suggesting the diagnosis of secondary or atypical Parkinsonism.
2. Subject has moderately or severely disabling dyskinesias for greater than 25% of the waking day
3. Subjects who have significant neurological symptoms not accounted for by Parkinson's disease
4. Subjects who are taking Sinemet® CR, Parcopa®, concomitant COMT inhibitors (i.e., entacapone or tolcapone), Stalevo®, or benserazide containing levodopa preparations Madopar® or Prolopa®.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: XenoPort, Inc.
• Investigators: Study Director: Dan Chen, M.D., XenoPort, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 26, 2010
• First Submitted That Met QC Criteria: July 27, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination
• Other Study ID Numbers: XP-C-069; XenoPort (Other Identifier: XenoPort)