Clinical trial NCT01411137: Carbidopa-Levodopa (CD-LD) ER Alone or in Combination With CD-LD IR to IPX066 Followed by IPX066 Extension Safety Study
Official title: An Open Label Conversion Study of Carbidopa-Levodopa (CD-LD) Extended-Release Taken Alone or in Combination With CD-LD Immediate Release to IPX066 Followed by an Open-Label Extension Safety Study of IPX066 in Advanced PD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Impax Laboratories, LLC
Sponsor class: INDUSTRY
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2011-08-08
Enrollment: 43
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study had three distinct parts and is described as follows:

Part 1:

* To evaluate the dose conversion from CD-LD ER taken alone or in combination with CD-LD IR to IPX066 in subjects with advanced PD
* To evaluate the utility of the Objective Parkinson's Disease Measurement (OPDM), an exploratory computer-based system, in assessing dexterity and mobility in a subset of PD subjects.

Part 2:

• To evaluate the long-term safety and clinical utility of IPX066 under open-label conditions in eligible subjects who successfully completed Part 1 of the study.

Part 3:

• To further evaluate the long-term safety of IPX066 in eligible subjects who successfully completed Part 2.

Detailed description: Part 1: This study was a multicenter, open-label study. Subjects were to be converted from their previous CD-LD treatment to IPX066 over a 6-week period. Up to 40 subjects were to be enrolled in the study. Enrollment was defined as subjects who received study drug in Part 1 - Visit 1. Subjects were to be entered into one of two cohorts.

Approximately 24 subjects were to enroll in Cohort 1 (non-OPDM subjects) and up to 16 subjects at selected sites were to enroll in Cohort 2 (OPDM subjects). For the subjects enrolled in Cohort 2, along with the OPDM measurements, PK blood samples were also to be collected.

Part 2: Following the successful completion of Part 1 of the study, eligible subjects could participate in Part 2, a 6-month open-label extension study.

Part 3: Following the successful completion of Part 2 of the study, eligible subjects could participate in Part 3, an additional 6-month open-label extension study.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed with idiopathic PD without any known cause for Parkinsonism.
2. At least 30 years old at the time of PD diagnosis.
3. Currently being treated with:

   * an LD dosing frequency of at least four times a day
   * at least one dose of CD-LD ER daily
   * requiring a total daily LD dose of at least 400 mg
   * stable regimen for at least 4 weeks prior to Screening
4. 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.
5. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study.

Exclusion Criteria:

1. Pregnant or breastfeeding
2. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome.
3. Nonresponsive to LD therapy.
4. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation.
5. Planning to take during participation in the clinical study: any controlled-release LD product, additional CD or benserazide, entacapone or tolcapone, nonselective MAO inhibitors, or antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder.
6. Any evidence of suicidal behavior within 6 months of entering the study.
7. Allergic or hypersensitive to to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice.
8. History of or currently active psychosis.
9. Active or history of peptic ulcers 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.
12. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome and/or nontraumatic rhabdomyolysis.
13. Abnormal kidney function
14. Severe hepatic impairment.
15. Received any investigational medications during the 4 weeks prior to Screening.
16. Previously enrolled in IPX066 studies.

Primary outcomes:
measure: Patient Global Impression (PGI)
timeFrame: 6 months
measure: Clinical Global Impression (CGI)
timeFrame: 6 months
measure: Parkinson's Disease Questionnaire-8 (PDQ-8)
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Coastal Neurological Medical Group
state: California
city: Sunnyvale
country: United States
facility: The Parkinson's Institute
state: California
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Bingham Farms
country: United States
facility: Quest Research Institute
state: Michigan
city: Las Vegas
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Commack
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Long Island
state: New York
city: Milwaukee
country: United States
facility: Wisconsin Institute for Neurologic and Sleep Disorders
state: Wisconsin
Study officials:
affiliation: Impax Laboratories, LLC
name: Impax Study Director
role: STUDY_CHAIR
References:
citation: Tetrud J, Nausieda P, Kreitzman D, Liang GS, Nieves A, Duker AP, Hauser RA, Farbman ES, Ellenbogen A, Hsu A, Kell S, Khanna S, Rubens R, Gupta S. Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson's disease. J Neurol Sci. 2017 Feb 15;373:116-123. doi: 10.1016/j.jns.2016.11.047. Epub 2016 Nov 23.