A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066

A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson's Disease

This is a study to compare the efficacy of IPX066 and CLE in subjects with advanced Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: IPX066; Drug: CLE

Detailed Description

This is a randomized, double-blind, double-dummy, 2 treatment, 2-period crossover study followed by an open-label extension study period.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand Cedex 1, France, 63003
    • Hôpital Gabriel Montpied-Service de Neurologie A-
  • Marseille, France, 13385
    • Service de neurologie-Hôpital de la Timone-
• Germany
  • Achim, Germany, 28832
    • Praxis für Neurologie, Psychiatrie und Psychotherapie Achim
  • Bochum, Germany, 44805
    • Praxis Dres. Bitter/Schumann
  • München, Germany, 81675
    • Klinikum Rechts Der Isar Der Technischen Universität München
  • Stadtroda, Germany, 07646
    • Klinik für Neurologie, Stadtroda
  • Ulm, Germany, 89081
    • RKU, Neurologische Klinik der Universität Ulm
• Italy
  • Arcugnano, Italy, 36057
    • Casa di Cura Villa Margherita
  • Cassino, Italy, 03043
    • San Raffaele Cassino, San Raffaele Cassino,
  • Chieti, Italy, 66013
    • Dipartimento di Oncologia e Neuroscienze, Università G. D'Annunzio
  • Grosseto, Italy, 58100
    • Ospedale della Misericordia
  • Roma, Italy, 163
    • IRCCS San Raffaele Pisana
• United States
  • California
    • Fresno, California, United States, 93720
      • Margolin Brain Institute
    • Sunnyvale, California, United States, 94085
      • The Parkinson's Institute in Sunnyvale
  • Florida
    • Miami, Florida, United States, 33136
      • UM Movement Disorders Center
    • Port Charlotte, Florida, United States, 33980
      • Charlotte Neurological Services
    • Tampa, Florida, United States, 33606
      • USF Parkinson's and Movement Disorders Center
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • QUEST Research Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Health Systems
  • New York
    • Commack, New York, United States, 11725
      • Parkinson's Disease and Movement Disorders Center of Long Island
    • Kingston, New York, United States, 12401
      • Kingston Neurological Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Neurology, Inc
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Neurological Associates
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosed with idiopathic Parkinson's Disease (PD).
2. At least 30 years old at the time of PD diagnosis.

3. Currently being treated with carbidopa/levodopa/entacapone (CLE) and on a stable regimen of conventional LD for at least 4 weeks and:

   • Requiring a total daily levodopa (LD) dose of at least 400 mg
   • Having a minimum dosing frequency of four times per day.
   • Individual CD-LD or CLE doses that contain an LD dose which is a multiple of 50 mg.
4. Able to differentiate "on" state from "off" state.
5. Have predictable "off" periods.
6. Amantadine, anticholinergics, selective monoamine oxidase (MAO) type B inhibitors (e.g., selegiline, rasagiline) or dopamine agonists are allowed as long as the doses and regimens have been stable for at least 4 weeks prior to Screening and the therapy is intended to be constant throughout the course of the study.
7. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month afterward.

Exclusion Criteria:

1. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome.
2. Nonresponsive to LD therapy.
3. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation.
4. Received within 4 weeks of Screening or planning to take during participation in the clinical study: any controlled-release LD product, tolcapone, apomorphine, nonselective MAO inhibitors, or antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder.
5. Allergy or hypersensitivity to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice.
6. History of or currently active psychosis.
7. Active or prior medical conditions such as peptic ulcers or prior surgical (e.g., bowel) procedures that would interfere with LD absorption.
8. Active or history of narrow-angle glaucoma.
9. History of malignant melanoma or a suspicious undiagnosed skin lesion.
10. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome or nontraumatic rhabdomyolysis.
11. Received any investigational medications during the 4 weeks prior to Screening.
12. Unable to swallow large pills (e.g., large vitamin pills).
13. Pregnant or breastfeeding.
14. Subjects who are unable to complete a symptom diary.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: IPX066-CLE-OLE; Dose conversion from CLE to IPX066, IPX066 (Part 1 Period 1), Open-label IPX066, CLE (Part 1 Period 2), OLE (Part 2)	Drug: IPX066; experimental product; Other Names: extended-release carbidopa-levodopa; Drug: CLE; active comparator; Other Names: carbidopa/levodopa/entacapone
Other: CLE-IPX066-OLE; Dose conversion from CLE to IPX066, CLE (Part 1 Period 1), Open-label IPX066, IPX066 (Part 1 Period 2), OLE (Part 2)	Drug: IPX066; experimental product; Other Names: extended-release carbidopa-levodopa; Drug: CLE; active comparator; Other Names: carbidopa/levodopa/entacapone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of "OFF" Time During Waking Hours	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean percentage of "OFF" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.	3 days of data immediately prior to the end of each 2 week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total "OFF" Time During Waking Hours	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "Off" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.	3 days of data immediately prior to the end of each 2 week treatment period
Total "On" With No Troublesome Dyskinesia	Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "On" with No Troublesome Dyskinesia was calculated. "On" Time is when medication is providing benefit with regard to mobility, slowness, and stiffness.	3 days of data immediately prior to the end of each 2 week treatment period
UPDRS Part II Plus Part III	Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). Part II consists of 14 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 72. Part III consists of 27 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 108. The UPDRS Part II Plus Part III scores ranged from 0 (no problems with daily living or mobility) to 180 (severe problems with daily living and mobility.	End of each double-blind treatment period.
Subject Preference	Subjects who completed both treatments were asked to indicate a preference for Treatment Period 1 or Treatment Period 2 or no preference. Preferences for a particular treatment period were mapped to the associated treatment and reported.	End of Study (week 11)

Collaborators and Investigators

• Sponsor: Impax Laboratories, LLC

Publications and helpful links

General Publications

• Morgan JC, Dhall R, Rubens R, Khanna S, Gupta S. Dosing Patterns during Conversion to IPX066, Extended-Release Carbidopa-Levodopa (ER CD-LD), in Parkinson's Disease with Motor Fluctuations. Parkinsons Dis. 2018 Oct 22;2018:9763057. doi: 10.1155/2018/9763057. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: May 24, 2010
• First Submitted That Met QC Criteria: May 24, 2010
• First Posted (Estimate): May 26, 2010

Study Record Updates

• Last Update Posted (Actual): October 29, 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; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination; Entacapone
• Other Study ID Numbers: IPX066-B09-06

Plan for Individual participant data (IPD)

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