Clinical trial NCT00869791: A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
Official title: A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's
Lead sponsor: Impax Laboratories, LLC
Sponsor class: INDUSTRY
First posted: 2009-03-26
Enrollment: 27
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study evaluated the pharmacokinetics, motor effects, and assessed the safety of IPX066 compared with an immediate-release cabridopa-levodopa formulation in subjects with advanced Parkinson's disease.

Detailed description: This was a randomized, multicenter, open-label, single and multiple oral dose, two-treatment, two-period, crossover study in LD-experienced subjects with Parkinson's disease (PD). Subjects received 7 days of one treatment (IPX066 or IR CD-LD) followed by an approximate 7-day washout period followed by another 7 days of the other treatment (IR CD-LD or IPX066). During the approximate 7-day washout period, subjects took their prestudy CD-LD regimen. Pharmacokinetic and efficacy/pharmacodynamic measurements were done on Days 1 and 8. Safety measures (electrocardiograms \[ECGs\], clinical laboratory tests, vital signs, adverse events \[AEs\], and concomitant medications) were evaluated over the course of the study.

Eligibility criteria: Inclusion Criteria:

1. Male or female diagnosed with idiopathic PD, without any known cause for Parkinsonism.
2. If female and of childbearing potential, subject should be abstinent or continuing to practice and willing to continue throughout the study with appropriate contraceptives (defined as Nova ring, oral, injected, transdermal patch, implanted, or barrier). The subject must agree to take every precaution to ensure that pregnancy will not occur during the study.
3. At least 30 years old at the time of diagnosis of PD.
4. Mini Mental State Examination (MMSE) ≥ 26 at Screening Visit.
5. A responder to LD and currently being chronically treated with stable dosage of commercially available standard, orally disintegrating, or controlled-release CD LD for at least 1 month.
6. Must have predictable fluctuations between "on" and "off" states.
7. Hoehn and Yahr Stage I-IV when "on".
8. Able to provide informed consent and willing to sign Health Insurance Portability and Accountability Act (HIPAA) authorization.
9. Able and willing to comply with the protocol, including availability for all scheduled study visits and blood sample collections.

Exclusion Criteria:

1. Pregnant or breastfeeding.
2. Diagnosed with atypical parkinsonism.
3. History, physical findings or laboratory results suggesting a diagnosis other than PD.
4. Allergic or nonresponsive to previous CD-LD therapy.
5. Any medical (e.g., liver or kidney impairment, peptic ulcer) or condition/history that, in the Investigator's opinion, may jeopardize the subject's safety.
6. Exposure to any investigational agent within 30 days prior to Visit 1.
7. Donated blood or plasma within 28 days.
8. Had prior functional neurosurgical treatment for PD (ablation or Deep Brain Stimulation).

Primary outcomes:
measure: Pharmacokinetics Measurements to Determine Cmax for Carbidopa (CD) and Levodopa (LD) Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
timeFrame: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm 2 (CD-LD IR first, washout, then IPX066)
measure: Pharmacokinetics Measurements to Determine Tmax for Levodopa and Carbidopa Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
timeFrame: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
measure: Pharmacokinetics Measurements to Determine Area Under the Concentration-time Curve for the Dosing Interval for LD and CD Concentrations From Blood Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Treatment Arms.
timeFrame: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
Secondary outcomes:
measure: 8-Hour Efficacy Using Day 1 Tapping
timeFrame: Day 1 of each treatment period - three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period
measure: 8-Hour Efficacy Using Day 1 Unified Parkinson's Disease Rating Scale Part III Score
timeFrame: Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
measure: Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for Each Treatment Period
timeFrame: Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
measure: "Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary
timeFrame: Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM
Other outcomes:
Locations:
city: Hayward
country: United States
facility: IMPAX Laboratories
state: California
Study officials:
affiliation: Impax Laboratories, LLC
name: Impax Study Director
role: STUDY_DIRECTOR
References:
citation: Hauser RA, Ellenbogen AL, Metman LV, Hsu A, O'Connell MJ, Modi NB, Yao HM, Kell SH, Gupta SK. Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease. Mov Disord. 2011 Oct;26(12):2246-52. doi: 10.1002/mds.23861. Epub 2011 Jul 13.