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

Phase 3

Completed

• Conditions: Parkinson's Disease
• Interventions: Drug: IPX066; Drug: CLE

• Registration Number: NCT01130493
• Lead Sponsor: Impax Laboratories, LLC

Brief Summary

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

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 Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-05-24
• Study First Submitted QC: 2010-05-24
• Study First Posted: 2010-05-26
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Disposition First Submitted: 2013-09-27
• Disposition First Submitted QC: 2013-09-27
• Disposition First Posted: 2013-10-28
• Results First Submitted: 2016-08-03
• Results First Submitted QC: 2017-08-15
• Status Verified: 2017-09
• Results First Posted: 2017-09-13
• Last Update Submitted: 2019-10-25
• Last Update Posted: 2019-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
CLE-IPX066-OLE	IPX066	Dose conversion from CLE to IPX066, CLE (Part 1 Period 1), Open-label IPX066, IPX066 (Part 1 Period 2), OLE (Part 2)
IPX066-CLE-OLE	CLE	Dose conversion from CLE to IPX066, IPX066 (Part 1 Period 1), Open-label IPX066, CLE (Part 1 Period 2), OLE (Part 2)
CLE-IPX066-OLE	CLE	Dose conversion from CLE to IPX066, CLE (Part 1 Period 1), Open-label IPX066, IPX066 (Part 1 Period 2), OLE (Part 2)
IPX066-CLE-OLE	IPX066	Dose conversion from CLE to IPX066, IPX066 (Part 1 Period 1), Open-label IPX066, CLE (Part 1 Period 2), OLE (Part 2)

Primary Outcome Measures

Name	Time	Method
Percentage of "OFF" Time During Waking Hours	3 days of data immediately prior to the end of each 2 week treatment period	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.

Secondary Outcome Measures

Name	Time	Method
UPDRS Part II Plus Part III	End of each double-blind treatment period.	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.
Total "On" With No Troublesome Dyskinesia	3 days of data immediately prior to the end of each 2 week treatment period	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.
Total "OFF" Time During Waking Hours	3 days of data immediately prior to the end of each 2 week treatment period	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.
Subject Preference	End of Study (week 11)	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.

Trial Locations

Locations (24)

Margolin Brain Institute; 🇺🇸 Fresno, California, United States

Charlotte Neurological Services; 🇺🇸 Port Charlotte, Florida, United States

UM Movement Disorders Center; 🇺🇸 Miami, Florida, United States

University Neurology, Inc; 🇺🇸 Cincinnati, Ohio, United States

Sentara Neurological Associates; 🇺🇸 Virginia Beach, Virginia, United States

Kingston Neurological Associates; 🇺🇸 Kingston, New York, United States

Booth Gardner Parkinson's Care Center; 🇺🇸 Kirkland, Washington, United States

Service de neurologie-Hôpital de la Timone-; 🇫🇷 Marseille, France

Praxis Dres. Bitter/Schumann; 🇩🇪 Bochum, Germany

Praxis für Neurologie, Psychiatrie und Psychotherapie Achim; 🇩🇪 Achim, Germany

Klinikum rechts der Isar der Technischen Universität München; 🇩🇪 München, Germany

RKU, Neurologische Klinik der Universität Ulm; 🇩🇪 Ulm, Germany

Casa di Cura Villa Margherita; 🇮🇹 Arcugnano, Italy

San Raffaele Cassino, San Raffaele Cassino,; 🇮🇹 Cassino, Italy

University Health Systems; 🇺🇸 Las Vegas, Nevada, United States

Hôpital Gabriel Montpied-Service de Neurologie A-; 🇫🇷 Clermont-Ferrand Cedex 1, France

USF Parkinson's and Movement Disorders Center; 🇺🇸 Tampa, Florida, United States

Dipartimento di Oncologia e Neuroscienze, Università G. D'Annunzio; 🇮🇹 Chieti, Italy

Ospedale della Misericordia; 🇮🇹 Grosseto, Italy

Quest Research Institute; 🇺🇸 Bingham Farms, Michigan, United States

Klinik für Neurologie, Stadtroda; 🇩🇪 Stadtroda, Germany

IRCCS San Raffaele Pisana; 🇮🇹 Roma, Italy

The Parkinson's Institute in Sunnyvale; 🇺🇸 Sunnyvale, California, United States

Parkinson's Disease and Movement Disorders Center of Long Island; 🇺🇸 Commack, New York, United States