Back to resultsA Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IPX066
IR CD-LD
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's
Eligibility Criteria
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).
Sites / Locations
- IMPAX Laboratories
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Sequence 1
Sequence 2
Arm Description
Treatment Period 1: IPX066 - 7 days; Washout Period - 7 days; Treatment Period 2: IR CD-LD- 7 days
Treatment Period 1: IR CD-LD - 7 days; Washout period - 7 days; Treatment Period 2: IPX066- 7 days
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
8-Hour Efficacy Using Day 1 Tapping
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.
8-Hour Efficacy Using Day 1 Unified Parkinson's Disease Rating Scale Part III Score
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.
Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for 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.
"Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary
Subjects recorded state of "OFF" time using the Parkinson's Patient Diary
Full Information
NCT ID
NCT00869791
First Posted
March 24, 2009
Last Updated
October 25, 2019
Sponsor
Impax Laboratories, LLC
1. Study Identification
Unique Protocol Identification Number
NCT00869791
Brief Title
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
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Impax Laboratories, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sequence 1
Arm Type
Other
Arm Description
Treatment Period 1:
IPX066 - 7 days; Washout Period - 7 days;
Treatment Period 2:
IR CD-LD- 7 days
Arm Title
Sequence 2
Arm Type
Other
Arm Description
Treatment Period 1:
IR CD-LD - 7 days; Washout period - 7 days;
Treatment Period 2:
IPX066- 7 days
Intervention Type
Drug
Intervention Name(s)
IPX066
Other Intervention Name(s)
ER CD-LD
Intervention Description
experimental drug product: extended-release carbidopa-levodopa capsules
Intervention Type
Drug
Intervention Name(s)
IR CD-LD
Other Intervention Name(s)
immediate-release carbidopa-levodopa
Intervention Description
active comparator: immediate-release carbidopa-levodopa capsules
Primary Outcome Measure Information:
Title
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.
Description
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.
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)
Title
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.
Description
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.
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
Title
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.
Description
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.
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
Secondary Outcome Measure Information:
Title
8-Hour Efficacy Using Day 1 Tapping
Description
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.
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
Title
8-Hour Efficacy Using Day 1 Unified Parkinson's Disease Rating Scale Part III Score
Description
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.
Time Frame
Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
Title
Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for Each Treatment Period
Description
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.
Time Frame
Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
Title
"Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary
Description
Subjects recorded state of "OFF" time using the 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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Impax Study Director
Organizational Affiliation
Impax Laboratories, LLC
Official's Role
Study Director
Facility Information:
Facility Name
IMPAX Laboratories
City
Hayward
State/Province
California
ZIP/Postal Code
94544
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21755537
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.
Results Reference
background
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/21755537
Description
PebMed Abstract
Learn more about this trial
A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa
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