A Study To Evaluate The Safety And Efficacy Of IPX066 In Advanced Parkinson's Disease (ADVANCE-PD).

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

This is a study to evaluate the safety and efficacy of IPX066 in advanced Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: IPX066; Drug: IR CD-LD

Detailed Description

A randomized, double-blind, active-control, parallel-group 13-week comparison of IPX066 versus regular carbidopa-levodopa (CD-LD). Prior to randomization, subjects on a stable regular LD regimen will enter a 3-week dose-adjustment period for IR CD-LD, followed by a 6-week dose-conversion period to IPX066.

• Study Type: Interventional
• Enrollment (Actual): 471
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 3X5
    • Investigator 26
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Investigator 24
    • Ottawa, Ontario, Canada, K1G 4G3
      • Investigator 18
• France
  • Alsace
    • Strasbourg Cedex, Alsace, France, 67091
      • Investigator 32
  • Bourgogne
    • Dijon, Bourgogne, France, 21000
      • Investigator 22
  • Ile-de-france
    • Paris, Ile-de-france, France, 75013
      • Investigator 58
  • Midi-pyrenees
    • Toulouse, Midi-pyrenees, France, 31059
      • Investigator 33
  • NORD Pas-de-calais
    • Lille, NORD Pas-de-calais, France, 59037
      • Investigator 52
• Germany
  • Berlin, Germany, 10437
    • Investigator 23
  • Berlin, Germany, 12163
    • Investigator 72
  • Berlin, Germany, 13088
    • Investigator 28
  • Berlin, Germany, 13353
    • Investigator 67
  • Dresden
    • Sachsen, Dresden, Germany, 1307
      • Investigator 30
  • Niedersachsen
    • Westerstede, Niedersachsen, Germany, 26655
      • Investigator 27
• Poland
  • Katowice, Poland, 40-546
    • Investigator 34
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Investigator 48
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-718
      • Investigator 59
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-530
      • Investigator 37
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-777
      • Investigator 36
  • Wielkopoloskie
    • Mosina, Wielkopoloskie, Poland, 62-050
      • Investigator 35
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-215
      • Investigator 54
• Romania
  • Brasov, Romania, 500283
    • Investigator 68
  • Bucuresti, Romania, 20125
    • Investigator 62
  • Târgu Mureş, Romania, 540136
    • Investigator 63
  • Mures
    • Târgu-Mureş, Mures, Romania, 540136
      • Investigator 69
• Spain
  • Barcelona, Spain, 8028
    • Investigator 70
  • Barcelona, Spain, 8036
    • Investigator 57
  • Barcelona, Spain, 8190
    • Investigator 45
  • Madrid, Spain, 28006
    • Investigator 50
  • Madrid, Spain, 28922
    • Investigator 53
  • Barcelona
    • Terrassa, Barcelona, Spain, 8221
      • Investigator 43
• Ukraine
  • Donetsk, Ukraine, 83003
    • Investigator 71
  • Kharkiv, Ukraine, 61068
    • Investigator 44
  • Odessa, Ukraine, 65117
    • Investigator 66
  • Zaporozhye, Ukraine, 69035
    • Investigator 41
  • Dnipropetrovsk
    • Dnepropetrovsk, Dnipropetrovsk, Ukraine, 49005
      • Investigator 55
  • Vinnytsya
    • Vinnitsa, Vinnytsya, Ukraine, 21005
      • Investigator 56
  • Zaporizhzhya
    • Zaporozhye, Zaporizhzhya, Ukraine, 69600
      • Investigator 47
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Investigator 17
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Investigator 49
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigator 7
  • California
    • La Jolla, California, United States, 92037
      • Investigator 3
    • Sunnyvale, California, United States, 94085
      • Investigator 31
    • Torrance, California, United States, 90502
      • Investigator 6
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigator 51
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Investigator 10
  • Florida
    • Bradenton, Florida, United States, 34205
      • Investigator 64
    • Hollywood, Florida, United States, 33021
      • Investigator 61
    • Ocala, Florida, United States, 34471
      • Investigator 5
    • Port Charlotte, Florida, United States, 33980
      • Investigator 15
    • Port Charlotte, Florida, United States, 33980
      • Investigator 8
    • Saint Petersburg, Florida, United States, 33713
      • Investigator 4
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Investigator 46
  • Idaho
    • Boise, Idaho, United States, 83702
      • Investigator 38
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Investigator 19
    • Chicago, Illinois, United States, 60612
      • Investigator 40
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Investigator 39
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Investigator 29
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Investigator 1
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Investigator 21
  • New York
    • Albany, New York, United States, 12208
      • Investigator 25
    • Commack, New York, United States, 11725
      • Investigator 8
    • New York, New York, United States, 10032
      • Investigator 12
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Investigator 11
    • Raleigh, North Carolina, United States, 27607
      • Investigator 9
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Investigator 20
    • Toledo, Ohio, United States, 43614
      • Investigator 42
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
      • Investigator 60
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Investigator 14
  • Texas
    • Dallas, Texas, United States, 75390-9016
      • Investigator 16
    • Houston, Texas, United States, 77030-2744
      • Investigator 13
  • Washington
    • Tacoma, Washington, United States, 98405
      • Investigator 65
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Investigator 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosed with idiopathic PD.
2. At least 30 years old at the time of PD diagnosis.

3. Currently being treated with IR LD (CD-LD or benserazide-LD) and on a stable regimen of IR LD for at least 4 weeks and:

   • Requiring a total daily IR LD dose of at least 400 mg
   • Having a minimum dosing frequency of four times per day.
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 or planning to take during participation in the clinical study: any controlled-release LD product, additional CD (e.g., Lodosyn®) or benserazide (e.g. Serazide®), catechol-O-methyl transferase inhibitors (e.g., entacapone and tolcapone), nonselective MAO inhibitors, apomorphine, and antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder.
5. Allergic to Yellow Dye #5 (tartrazine).
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. A 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 and/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: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IPX066; Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IPX066.	Drug: IPX066; extended-release carbidopa-levodopa capsules; Other Names: ER CD-LD; Drug: IR CD-LD; immediate-release carbidopa-levodopa tablets; Other Names: immediate-release carbidopa-levodopa
Active Comparator: IR CD-LD; Following IR CD-LD dose adjustment and conversion to IPX066, subjects were assigned to Investigational product IR CD-LD (active comparator).	Drug: IPX066; extended-release carbidopa-levodopa capsules; Other Names: ER CD-LD; Drug: IR CD-LD; immediate-release carbidopa-levodopa tablets; Other Names: immediate-release carbidopa-levodopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of "Off" Time During Waking Hours at End of Study	Percentage of "off" time during waking hours at end of study is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."	22 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
"Off" Time	"Off" time hours is measured by using the Parkinson's disease diary. "Off" time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)."	22 weeks
"On" Time Without Troublesome Dyskinesia	"On" time without troublesome dyskinesiais measured by using the Parkinson's disease diary. "On" time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living."	22 weeks

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.
• Hauser RA, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M, Ondo W, O'Connell M, Gupta S; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol. 2013 Apr;12(4):346-56. doi: 10.1016/S1474-4422(13)70025-5. Epub 2013 Feb 26.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Parkinson's Disease
• 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: IPX066-B09-02

Plan for Individual participant data (IPD)

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