A Study to Assess the PK and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson's Disease

A Study to Assess the Pharmacokinetics and Pharmacodynamics of a Single Dose of IPX203 in Patients With Advanced Parkinson's Disease

This is a randomized, open-label, rater-blinded, multicenter, 3-treatment, 3 period, single-dose crossover study. Approximately 51 qualified immediate-release (IR) CD-LD-experienced advanced Parkinson's disease patients will be randomized to 1 of 3 dosing sequences.

Objectives:

• Assess the pharmacodynamics and pharmacokinetics (PK) of IPX203 (carbidopa and levodopa) in subjects with advanced Parkinson's disease.
• Characterize the safety of IPX203 in subjects with advanced Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: CD-LD IR; Drug: IPX203 180 mg; Drug: IPX203 270 mg; Drug: Rytary 195 mg; Drug: Rytary 145 mg

Detailed Description

IPX203 contains two different drugs called levodopa and carbidopa in one capsule.

• levodopa turns into a material called 'dopamine' in your brain. The dopamine helps to improve the symptoms of your Parkinson's disease.
• carbidopa belongs to a group of medicines called 'aromatic amino acid decarboxylase inhibitors'. It helps levodopa work more effectively by slowing the speed at which levodopa is broken down in your body.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Muhammad Ali Movement Disorder Center (MAMDC)
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials, Inc.
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinson's and Movement Disorder Institute
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Naples, Florida, United States, 34102
      • Collier Neurologic Specialists
    • Tampa, Florida, United States, 33613
      • University of South Florida Parkinson's Disease and Movement Disorder Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Movement Disorders Clinic
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Male or female subjects diagnosed with idiopathic PD with motor complications, who are currently being treated chronically with stable regimens of CD-LD.

Requiring at least 400 mg but not more than 1600 mg LD per day during the waking hours; and at least 100 mg but not more than 250 mg LD from IR CD-LD for the first morning dose.

Dosing frequency of IR CD-LD of at least 4 times daily excluding nighttime dosing.

Have an average of at least 2 hours per day "off" time during the waking hours and at least 1 hour "off" time per day, based on the PD diary collected for 3 consecutive days prior to Visit 1.

Exclusion criteria:

Have used first morning dose of controlled-release (CR) CD-LD or Rytary for at least 4 weeks prior to Visit 1.

Female subjects who are currently breastfeeding or lactating.

Had prior functional neurosurgical treatment for PD (ablation or deep brain stimulation) or if such procedure(s) are planned or anticipated during the study period.

Allergic to study drugs

History of medical conditions or of a prior surgical procedure that would interfere with LD absorption, such as gastrectomy or small-bowel resection.

History of peptic ulcer disease or upper gastrointestinal hemorrhage.

History of narrow angle glaucoma.

History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias; neuroleptic malignant syndrome; or nontraumatic rhabdomyolysis.

History of psychosis.

Employees or family members of the Investigator, study site, or Sponsor.

Subjects who, in the opinion of the clinical investigator, should not participate in the study.

Based on clinical assessment, subject does not adequately comprehend the terminology needed to complete the PD diary.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence 1; Subject received a single dose of IPX203 180 mg and/or IPX203 270mg in Period 1, a single dose of CD-LD IR in Period 2, and a single dose of Rytary 145 mg and/or Rytary 195 mg in Period 3.	Drug: CD-LD IR; CD-LD IR containing 25 mg carbidopa and 100 mg levodopa; Other Names: Sinemet; Drug: IPX203 180 mg; IPX203 containing 45 mg carbidopa and180 mg levodopa; Other Names: CD-LD ER 180 mg; Drug: IPX203 270 mg; IPX203 containing 67.5 mg carbidopa and 270 mg levodopa; Other Names: CD-LD ER 270 mg; Drug: Rytary 195 mg; Rytary 48.75Mg-195Mg Extended-Release Capsule; Drug: Rytary 145 mg; Rytary 36.25Mg-145Mg Extended-Release Capsule
Other: Sequence 2; Subject received a single dose of a single dose of CD-LD IR in Period 1, a single dose of Rytary 145 mg and/or Rytary 195 mg in Period 2, and a single dose of IPX203 180 mg and/or IPX203 270mg in Period 3.	Drug: CD-LD IR; CD-LD IR containing 25 mg carbidopa and 100 mg levodopa; Other Names: Sinemet; Drug: IPX203 180 mg; IPX203 containing 45 mg carbidopa and180 mg levodopa; Other Names: CD-LD ER 180 mg; Drug: IPX203 270 mg; IPX203 containing 67.5 mg carbidopa and 270 mg levodopa; Other Names: CD-LD ER 270 mg; Drug: Rytary 195 mg; Rytary 48.75Mg-195Mg Extended-Release Capsule; Drug: Rytary 145 mg; Rytary 36.25Mg-145Mg Extended-Release Capsule
Other: Sequence 3; Subject received a single dose of a single dose of Rytary 145 mg and/or Rytary 195 mg in Period 1, a single dose of IPX203 180 mg and/or IPX203 270mg in Period 2, and a single dose of CD-LD IR in Period 3.	Drug: CD-LD IR; CD-LD IR containing 25 mg carbidopa and 100 mg levodopa; Other Names: Sinemet; Drug: IPX203 180 mg; IPX203 containing 45 mg carbidopa and180 mg levodopa; Other Names: CD-LD ER 180 mg; Drug: IPX203 270 mg; IPX203 containing 67.5 mg carbidopa and 270 mg levodopa; Other Names: CD-LD ER 270 mg; Drug: Rytary 195 mg; Rytary 48.75Mg-195Mg Extended-Release Capsule; Drug: Rytary 145 mg; Rytary 36.25Mg-145Mg Extended-Release Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
"Off" time per the Assessment of Subject's Motor State	Up to 10 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of effect estimated using the timepoint at which an improvement of at least 4 points in the MDS-UPDRS Part III score from predose is first observed and continuing until the timepoint at which the improvement is no longer observed	Up to 10 hours
Change from predose value in the number of finger-taps at each timepoint	Up to 10 hours

Other Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events	Screening through end of study approximately 6 weeks per subject
Maximum concentration (Cmax)	Up to 10 hours
Area under the curve (AUC)	Up to 10 hours

Collaborators and Investigators

• Sponsor: Impax Laboratories, LLC

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 22, 2014

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: September 1, 2017

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: IPX203-B14-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No