- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00869791
A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
October 25, 2019 updated by: Impax Laboratories, LLC
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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California
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Hayward, California, United States, 94544
- IMPAX Laboratories
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female diagnosed with idiopathic PD, without any known cause for Parkinsonism.
- 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.
- At least 30 years old at the time of diagnosis of PD.
- Mini Mental State Examination (MMSE) ≥ 26 at Screening Visit.
- 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.
- Must have predictable fluctuations between "on" and "off" states.
- Hoehn and Yahr Stage I-IV when "on".
- Able to provide informed consent and willing to sign Health Insurance Portability and Accountability Act (HIPAA) authorization.
- Able and willing to comply with the protocol, including availability for all scheduled study visits and blood sample collections.
Exclusion Criteria:
- Pregnant or breastfeeding.
- Diagnosed with atypical parkinsonism.
- History, physical findings or laboratory results suggesting a diagnosis other than PD.
- Allergic or nonresponsive to previous CD-LD therapy.
- 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.
- Exposure to any investigational agent within 30 days prior to Visit 1.
- Donated blood or plasma within 28 days.
- Had prior functional neurosurgical treatment for PD (ablation or Deep Brain Stimulation).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Sequence 1
Treatment Period 1: IPX066 - 7 days; Washout Period - 7 days; Treatment Period 2: IR CD-LD- 7 days |
experimental drug product: extended-release carbidopa-levodopa capsules
Other Names:
active comparator: immediate-release carbidopa-levodopa capsules
Other Names:
|
Other: Sequence 2
Treatment Period 1: IR CD-LD - 7 days; Washout period - 7 days; Treatment Period 2: IPX066- 7 days |
experimental drug product: extended-release carbidopa-levodopa capsules
Other Names:
active comparator: immediate-release carbidopa-levodopa capsules
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: 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)
|
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data).
Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data and Multiple-Dose data.
|
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)
|
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.
Time Frame: 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
|
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data).
Time of maximum drug concentration (Tmax in hours) was estimated using Single-Dose data and Multiple-Dose data.
|
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
|
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.
Time Frame: 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
|
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data).
Area under the concentration-time curve for the dosing interval (AUC Tau) in hour*nanogram/milliliter was estimated using Single-Dose data and Multiple-Dose data.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
8-Hour Efficacy Using Day 1 Tapping
Time Frame: 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
|
Improvement in "Tapping: has been used as a surrogate endpoint for assessing subject being "On".
Finger Tapping: the number of times the subject could tap two counter keys 20 cm apart alternately in 1 minute with the most affected arm assessed every 30 minutes on Day 1. Subjects performed the 60-second tapping measurement three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period on Day 1 of each treatment period.
More hours "On" during treatment represented better outcome.
For the Tapping measurement, the protocol defined a 20% change from the average of the predose measurements as the time to "On."
Each half-hour interval counted as 0.5 hour.
Any measurement below a 20% improvement was considered time "Not On."
If patient required redosing then primary analyses adjusted for redosing in calculating the results.
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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
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8-Hour Efficacy Using Day 1 Unified Parkinson's Disease Rating Scale Part III Score
Time Frame: Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
|
To determine efficacy on Day 1 the UPDRS (unified Parkinson's disease rating) Part III score, a clinician-scored measure of motor function, was collected immediately predose and 1, 2, 3, 4, 5, 6, 7 and 8 h post dose.
The UPDRS Part III motor exam analyzes multiple motor functions like speech, facial expression, tremor, rigidity, movement, posture, gait etc.
Each parameter is assigned values from 0 to 4, with 0 being normal and 4 being the most affected.
The total range is 0 - 108, with lower scores indicating a better outcome.The average of post dose was calculated for day 1.
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Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
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Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for Each Treatment Period
Time Frame: Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
|
To determine 8h efficacy on Day 1 the on site investigator assessments of "ON", "OFF" and "state of dyskinesia" for each subject was collected predose (-1, -0.5, and 0 hours) every 30 min for up to 8 hours after dosing .
For all subjects duration of (1) OFF time (2) ON time without dyskinesia, (3) ON time with non-troublesome dyskinesia and (4) ON time with troublesome dyskinesia was calculated for both treatments.
Definition of "ON" was based on a 20% change from predose measure, and the results were analyzed in the standard manner of a two way crossover design.
The trial inclusion criteria included ability of subject to differentiate "ON" state from "OFF" state per investigator's assessment.
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Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
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"Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary
Time Frame: Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM
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Subjects recorded state of "OFF" time using the Parkinson's Patient Diary
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Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2008
Primary Completion (Actual)
June 1, 2009
Study Completion (Actual)
June 1, 2009
Study Registration Dates
First Submitted
March 24, 2009
First Submitted That Met QC Criteria
March 25, 2009
First Posted (Estimate)
March 26, 2009
Study Record Updates
Last Update Posted (Actual)
November 8, 2019
Last Update Submitted That Met QC Criteria
October 25, 2019
Last Verified
March 1, 2017
More Information
Terms related to this study
Keywords
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-B08-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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