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

• Register: EUCTR
• Last refreshed on: 4 January 2022
• Main ID: EUCTR2009-017238-39-DE
• Date of registration: 28/07/2010
• Prospective Registration: Yes
• Primary sponsor: Impax Laboratories, Inc., acting through its Impax Pharmaceuticals Division (Impax)
• Public title: A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson’s Disease
• Scientific title: A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson’s Disease
• Date of first enrolment: 16/09/2010
• Target sample size: 96
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017238-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
Part 1:
1. Able to understand and willing to sign an ICF and Health Insurance Portability and Accountability Act (HIPAA) authorization or local equivalent, if applicable.
2. Diagnosed with idiopathic PD meeting United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria (Appendix M), without any known cause for Parkinsonism.
3. At least 30 years old at the time of PD diagnosis.
4. Hoehn and Yahr Staging I-IV in the “on” state (Appendix N).
5. Mini-Mental State Exam (MMSE, Appendix O) = 26 at Screening.
6. Currently being treated with CLE in a dosing regimen which includes an immediate release LD product (e.g., Stalevo® or standard Sinemet® 25 mg-100 mg plus entacapone). Subject must be on a stable regimen of CLE (or benserazide-levodopa-entacapone) for at least 4 weeks at:
• a total daily levodopa dose of at least 400 mg
• a minimum CLE 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.
7. Able to differentiate “on” state from “off” state as defined by at least 75% concordance with an experienced rater in “on/off” ratings for at least four ratings over the 4-hour training period. The concordance must include at least one “on” and one “off” rating and must be achieved within two 4-hour training sessions.
8. Have predictable “off” periods defined by a “yes” response to Question #36 on the UPDRS.
9. Prior to the Screening Visit, the subject should have an average of at least 2.5 cumulative hours per day of “off” time during the waking hours for the last 2 weeks (by history). At Visit 1, the subject must have an average of at least 2.5 hours over 3 days and at least 1 hour each day of “off” time based on the 3-day PD diaries recorded on the 3 consecutive days immediately prior to Visit 1.
10. For subjects participating in Cohort 1 at least 10% increase in finger tapping rate (number of taps over a 1-minute period) during the “on” state when compared to the “off” state at Screening.
11. Concomitant therapy with amantadine, anticholinergics, selective monoamine oxidase (MAO) type B inhibitors (e.g., selegiline, rasagiline) or dopamine agonists is 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.
12. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study. Medically acceptable methods of contraception that may be used by the subject and/or partner include, but are not limited to: abstinence, oralcontraception, NuvaRing® or transdermal systems, diaphragm with vaginal spermicide, intrauterine device, condom and partner using vaginal spermicide, surgical sterilization (6 months), progestin implant or injection, postmenopausal female (no menstrual period for > 2 years) or vasectomy (> 6 months).
13. Able and willing to comply with the protocol, including availability for all scheduled clinic visits, diary data and blood sample collections, and telephone calls.

Part 2:
Each subject must meet the following inclusion criteria in order to be enrolled in Part 2 of the study:
1. Successful completion of Part 1 of IPX066-B09-06 as of June 30, 2011.
2. In the opinion of the Investigator, the Parkinson's disease diagnosis is still valid and the subject remains eligible for LD therapy.
Are the trial subjects under 18? no
Number of subjects for this age
Exclusion criteria:
Part 1:
1. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome (e.g., vascular, toxin- or medication-induced, metabolic, or infectious) or other neurodegenerative disorder with Parkinsonism (e.g., progressive supranuclear palsy, corticobasal degeneration, multiple-system atrophy).
2. Nonresponsive to LD therapy.
3. Combined total score of = 5 on Questions #32, #33, and #34 of the UPDRS or a score of = 3 on Question #33 of the UPDRS.
4. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation), or such procedures are anticipated during study participation.
5. 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.
6. Planning to take during participation in the clinical study: Any CD or LD products not provided by the study, e.g., Lodosyn®, benserazide (Serazide®), Sinemet® CR or any controlled-release LD products, Parcopa® or any fast-dissolving LD-containing products, or any entacapone not provided by the study.
7. Allergy or hypersensitivity to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice.
8. Active or history of psychosis.
9. Active or history of peptic ulcer or surgical procedure of the stomach, the small intestine or the large intestine.
10. Active or history of narrow-angle glaucoma.
11. History of malignant melanoma or a suspicious undiagnosed skin lesion which, in the opinion of the Investigator, could be melanoma.
12. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, neuroleptic malignant syndrome or nontraumatic rhabdomyolysis.
13. Abnormal kidney function (e.g., serum creatinine level = 1.5 times the upper limit of normal) at Screening or requires dialysis.
14. Severe hepatic impairment.
15. Received any investigational medications during the 4 weeks prior to Screening.
16. Donated blood or plasma within 28 days prior to Visit 1 or planning to donate blood or plasma during the study or within 4 weeks after completing the study.
17. Unable to swallow large pills (e.g., large vitamin pills).
18. Previously enrolled in IPX066 studies.
19. Pregnant or breastfeeding.
20. Employees or family members of the Investigator, study site, or sponsor.
21. Unable to complete the PD diary.
22. In the opinion of the clinical Investigator, the subject should not participate in the study.

Part 2:
Each subject must be free of the following exclusion criteria in order to be enrolled in the study:
1. Received any investigational medications other than IPX066 after enrollment in Part 1 of this study.
2. Anticipates functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) during study participation.
3. Received within 4 weeks prior to Baseline Visit or planning to take the following medications during study participation: nonselective monoamine oxidase (MAO) inhibitors (with the exception of rasagiline).
4. In the opinion of the Investigator, should not participate in the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic Parkinson’s Disease (paralysis agitans)
MedDRA version: 14.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: IPX066
Product Code: IPX066-95
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 23.75-
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 95-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: IPX066
Product Code: IPX066-145
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 36.25-
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 145-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: IPX066
Product Code: IPX066-195
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 48.75-
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 195-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: IPX066
Product Code: IPX066-245
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 61.25-
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 245-
Pharmaceutical form of the placebo: Capsu

Primary Outcome(s)

Primary end point(s): The primary efficacy parameter for this study is the percent “off” time during waking hours based on subject PD diaries collected at the end of each doubleblind treatment period. For each day it is calculated as the number of half-hour intervals in which “off” is checked. The percent “off” time is defined as the total “off” time divided by the total time not “asleep” (i.e., waking hours) from the subject PD diaries completed for the 3 days immediately prior to the visit.

Secondary Objective: None

Main Objective: Part 1:
1. To compare the efficacy of IPX066 and Carbidopa/Levodopa/Entacapone in subjects with advanced Parkinson’s disease
2. To assess the pharmacokinetics and pharmacodynamics of IPX066 and Carbidopa/Levodopa/Entacapone in subjects with advanced Parkinson’s disease

Part 2:
To evaluate the long-term safety and clinical utility of IPX066 in subjects who successfully complete Part 1 of this study under open-label conditions.

Secondary ID(s)

IPX066-B09-06

2009-017238-39-FR

Ethics review

Status: Approved
Approval date: 16/09/2010
Contact:

Results

• Results available: Yes
• Date Posted: 14/10/2017
• Date Completed: 12/01/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017238-39/results