A Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease

Parkinson's Disease Clinical Trial

— APEX-PD  

Official title:

A Placebo-Controlled Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00880620
• Other study ID #: IPX066-B08-05
• Status: Completed
• Phase: Phase 3
• Start date: April 2009
• Est. completion date: November 2010

Study information

• Verified date: August 2017
• Source: Impax Laboratories, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study examines the efficacy of three doses of IPX066 as compared to placebo in Parkinson's disease.

Description:

A randomized, double-blind, placebo-controlled, fixed-dose, parallel-arm study of three doses of IPX066 versus placebo.

Total of 427 subjects were screened and 381 were randomized and received one of the four treatment groups (1) placebo (N=92), (2) IPX066 145 mg LD (N=87) (3) IPX066 245 mg LD (N=104) (4) IPX066 390 mg LD (N=98) three times a day.

Study duration is approximately 30 weeks for each subject including 4 weeks of titration (up to 3 weeks of dose escalation and I week of stabilization for safe escalation to the allocated dose), and 26 weeks of maintenance.

During the titration phase:

The following dose strengths were used to titrate up to the final three strengths that were assigned to the three IPX066 treatment arms.

IPX066 95 mg LD capsule containing 95 mg LD and 23.75 mg CD. IPX066 145 mg LD capsule containing 145 mg LD and 36.25 mg CD. IPX066 195 mg LD capsule containing 195 mg LD and 48.75 mg CD. IPX066 245 mg LD capsule containing 245 mg LD and 61.25 mg CD.

During the maintenance phase:

IPX066 145 mg LD treatment arm received 145 mg LD and 36.25 mg CD. IPX066 245 mg LD treatment arm received 245 mg LD and 61.25 mg CD. IPX066 390 mg LD treatment arm received 390 mg LD and 97.50 mg CD.

Primary efficacy outcome measure was change from baseline in the sum of UPDRS Part II and Part III scores at the end of study or last value reported if subject discontinued prematurely.

Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: November 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

1. Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization or local equivalent if applicable.

2. Diagnosed with idiopathic PD.

3. LD-naïve: defined as subjects not exposed to LD or catechol-O-methyl transferase inhibitors for more than 30 days and the exposure is not within 4 weeks prior to study enrollment.

4. If currently taking anticholinergic therapy, amantadine, or a monoamine oxidase type B (MAO-B) inhibitor, maintains a stable regimen for at least 4 weeks prior to Baseline, and agrees to maintain the stable regimen throughout study participation.

5. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study.

6. Able and willing to comply with the protocol, including availability for all scheduled clinic visits and telephone calls.

Exclusion Criteria:

1. Pregnant or breastfeeding.

2. Diagnosed with atypical Parkinsonism or any known secondary parkinsonian syndrome.

3. Prior functional neurosurgical treatment for PD or if such procedures are anticipated during study participation.

4. Use of nonselective MAO inhibitors.

5. Use of dopamine agonists within 30 days prior to Screening.

6. Unable to tolerate a placebo regimen, in the Investigator's opinion.

7. Treatment of psychosis with any antipsychotic.

8. History of seizure or epilepsy.

9. Active or prior medical condition or prior surgical procedure that would interfere with LD absorption.

10. History of narrow-angle glaucoma.

11. Subjects with a history of malignant melanoma.

12. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome.

13. Received any investigational medications during the 30 days prior to Screening.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Placebo
Placebo
• IPX066 95 mg LD
IPX066 capsule containing 95 mg LD/23.75 mg CD
• IPX066 145 mg LD
IPX066 capsule containing 145 mg LD/36.25 mg CD
• IPX066 195 mg LD
IPX066 capsule containing 195 mg LD/48.75 mg CD
• IPX066 245 mg LD
IPX066 capsule containing 245 mg LD/61.25 mg CD

Locations

Country	Name	City	State
Canada	Movement Disorders Clinic, Glenrose Rehabilitation Hospital	Edmonton	Alberta
Canada	London Health Science Center	London	Ontario
Canada	Ottawa Hospital Civic Site	Ottawa	Ontario
Canada	Parkinson's and Neurodegenerative Disorders Clinic	Ottawa	Ontario
Canada	Memory and Motor Skills Clinic	Quebec
Canada	University of Sherbrooke	Sherbrooke	Quebec
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Saint Boniface Clinic	Winnipeg	Manitoba
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	West Tallin Central Hopsital	Tallinn
Latvia	Gailezers hospital	Riga
Latvia	P.Stradina university hospital	Riga
Lithuania	Kaunas Medical University Hospital	Kaunas
Lithuania	Siauliai Regional Hospital	Siauliai
Lithuania	Vilnius University Centre of Gerontology and Rehabilitation	Vilnius
Lithuania	Vilnius University Emergency Hospital	Vilnius
Lithuania	Vilnius University Hospital Santariskiu klinikos	Vilnius
Romania	Psychiatry and Neurology Hospital, Neurology Department	Brasov
Romania	Colentina Clinical Hospital Bucharest, II Neurology Department	Bucharest
Romania	County Emergency Clinical Hospital Cluj-Napoca, I Neurology Clinic	Cluj Napoca
Romania	CFR Clinical Hospital Constanta	Constanta
Romania	Clinical Rehabilitation Hospital Iasi, Neurology Department	Iasi
Romania	County Clinical Emergency Hospital, Targu Mures, II Neurology Department,	Targu Mures
Romania	County Clinical Emergency Hospital Timisoara	Timisoara
Ukraine	Neurology department of Regional hospital named after Mechnikov	Dnepropetrovsk
Ukraine	Department of Neurological Diseases and Medical Genetic of Donetsk National Medical University	Donetsk
Ukraine	Department of Psychiatry and Medical Psychology of Donetsk National Medical University	Donetsk
Ukraine	1st neurology department of Central Clinical Hospital of Ukrzaliznytsya	Kharkiv
Ukraine	Institute of Gerontology Parkinson's Disease Center	Kiev
Ukraine	Neurology department of Lviv regional clinical hospital	Lviv
Ukraine	Neurology department of Medical Dental Academy based on Poltava regional hospital	Poltava
Ukraine	Neurology department of Vinnitsa Medical University	Vinnitsa
Ukraine	Neurology department, Zaporozhye State Medical University	Zaporozhye
United States	Quest Research Institute	Bingham Farms	Michigan
United States	University of Alabama at Birmingham, Dept. of Neurology	Birmingham	Alabama
United States	Idaho Elks Rehabilitation Hospital	Boise	Idaho
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Bradenton Research Center, Inc.	Bradenton	Florida
United States	Rush University Medical Center, Dept. of Neurological Sciences	Chicago	Illinois
United States	Duke University Medical Center Movement Disorders Center	Durham	North Carolina
United States	Collaborative NeuroScience Network, Inc.	Garden Grove	California
United States	Struthers Parkinson's Center	Golden Valley	Minnesota
United States	Sunrise Clinical Research, Inc.	Hollywood	Florida
United States	Baylor College of Medicine, Parkinson's Disease Center	Houston	Texas
United States	Landon Center on Aging, Dept. of Neurology, Parkinson's Disease Center	Kansas City	Kansas
United States	Coastal Neurological Medical Group	La Jolla	California
United States	Coordinated Clinical Research	La Jolla	California
United States	Wisconsin Institute for Neurologic and Sleep Disorders	Milwaukee	Wisconsin
United States	UMDNJ Robert Wood Johnson Medical Center, Department of Neurology	New Brunswick	New Jersey
United States	Yale Neurology Clinics, Temple Medical Center	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Renstar Medical Research	Ocala	Florida
United States	HOPE Research Institute, LLC	Phoenix	Arizona
United States	Charlotte Neurological Services	Port Charlotte	Florida
United States	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida
United States	The Parkinson's Institute	Sunnyvale	California
United States	State University of New York Upstate Medical University, Dept. of Neurology	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	University of Toledo	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Impax Laboratories, LLC

Countries where clinical trial is conducted

United States,  Canada,  Estonia,  Latvia,  Lithuania,  Romania,  Ukraine, 

References & Publications (1)

Pahwa R, Lyons KE, Hauser RA, Fahn S, Jankovic J, Pourcher E, Hsu A, O'Connell M, Kell S, Gupta S; APEX-PD Investigators. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord. 2014 Feb;20(2):142-8. doi: 10.1016/j.parkreldis.2013.08.017. Epub 2013 Sep 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30	Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at Week 30 (End of Study).; Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome.; Subscales II and III were summed: Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25	Week 30
Secondary	Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score	Change from Baseline in Parkinson's disease Questionnaire 39 (PDQ-39) at Weeks 4, 9, 16, 23 and 30 or early discontinuation was collected. The PDQ-39 is a self-reported questionnaire consisting of 39 questions regarding the subjects mobility and the responses consist of "Never" (better in outcome), (value 0), "Occasionally" (value 1), "Sometimes" (value 2), , "Often" (value 3), and "Always" (value 4), (worse in outcome). The minimum possible score is "0" and the maximum is "156". The outcome measure calculated was the change from baseline to end of study in mean PDQ-39 score. Negative values indicate a better result.	Baseline and Week 30 (or End of Study)