Parkinson's Disease
Conditions
Keywords
Parkinson's Disease
Brief summary
This is a study to evaluate the safety and efficacy of IPX066 in advanced Parkinson's disease.
Detailed description
A randomized, double-blind, active-control, parallel-group 13-week comparison of IPX066 versus regular carbidopa-levodopa (CD-LD). Prior to randomization, subjects on a stable regular LD regimen will enter a 3-week dose-adjustment period for IR CD-LD, followed by a 6-week dose-conversion period to IPX066.
Interventions
Sponsors
Impax Laboratories, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with idiopathic PD. 2. At least 30 years old at the time of PD diagnosis. 3. Currently being treated with IR LD (CD-LD or benserazide-LD) and on a stable regimen of IR LD for at least 4 weeks and: * Requiring a total daily IR LD dose of at least 400 mg * Having a minimum dosing frequency of four times per day. 4. Able to differentiate on state from off state. 5. Have predictable off periods. 6. Amantadine, anticholinergics, selective monoamine oxidase (MAO) type B inhibitors (e.g., selegiline, rasagiline) or dopamine agonists are 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. 7. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month afterward.
Exclusion criteria
1. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome. 2. Nonresponsive to LD therapy. 3. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation. 4. Received within 4 weeks or planning to take during participation in the clinical study: any controlled-release LD product, additional CD (e.g., Lodosyn®) or benserazide (e.g. Serazide®), catechol-O-methyl transferase inhibitors (e.g., entacapone and tolcapone), nonselective MAO inhibitors, apomorphine, and antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder. 5. Allergic to Yellow Dye #5 (tartrazine). 6. History of or currently active psychosis. 7. Active or prior medical conditions such as peptic ulcers or prior surgical (e.g., bowel) procedures that would interfere with LD absorption. 8. Active or history of narrow-angle glaucoma. 9. A history of malignant melanoma or a suspicious undiagnosed skin lesion. 10. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome and/or nontraumatic rhabdomyolysis. 11. Received any investigational medications during the 4 weeks prior to Screening. 12. Unable to swallow large pills (e.g., large vitamin pills). 13. Pregnant or breastfeeding. 14. Subjects who are unable to complete a symptom diary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Off Time During Waking Hours at End of Study | 22 weeks | Percentage of off time during waking hours at end of study is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Off Time | 22 weeks | Off time hours is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease). |
| On Time Without Troublesome Dyskinesia | 22 weeks | On time without troublesome dyskinesiais measured by using the Parkinson's disease diary. On time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living. |
Countries
Canada, France, Germany, Poland, Romania, Spain, Ukraine, United States
Participant flow
Recruitment details
Study period was form September 29, 2009 to January 19, 2011.
Pre-assignment details
Prior to randomization, subjects needed to complete a 3-week dose adjustment of IR CD-LD followed by 6-week dose conversion to IPX066.
Participants by arm
| Arm | Count |
|---|---|
| IPX066 Investigational product IPX066 | 201 |
| Carbidopa-Levodopa Immediate-release carbidopa and levodopa | 192 |
| Total | 393 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| IPX066 Dose Conversion | Adverse Event | 23 | 0 |
| IPX066 Dose Conversion | Death | 2 | 0 |
| IPX066 Dose Conversion | Lack of Efficacy | 13 | 0 |
| IPX066 Dose Conversion | Protocol Violation | 4 | 0 |
| IPX066 Dose Conversion | Various | 3 | 0 |
| IPX066 Dose Conversion | Withdrawal by Subject | 12 | 0 |
| IR CD-LD Dose Adjustment | Adverse Event | 0 | 3 |
| IR CD-LD Dose Adjustment | Noncompliance with study drug | 0 | 1 |
| IR CD-LD Dose Adjustment | Protocol Violation | 0 | 1 |
| IR CD-LD Dose Adjustment | Various | 0 | 9 |
| IR CD-LD Dose Adjustment | Withdrawal by Subject | 0 | 7 |
| Maintenance - Double Blind Treatment | Adverse Event | 3 | 3 |
| Maintenance - Double Blind Treatment | Lack of Efficacy | 2 | 2 |
| Maintenance - Double Blind Treatment | Lost to Follow-up | 0 | 1 |
| Maintenance - Double Blind Treatment | Noncompliance with study drug | 0 | 1 |
| Maintenance - Double Blind Treatment | Protocol Violation | 1 | 1 |
| Maintenance - Double Blind Treatment | Various | 4 | 0 |
| Maintenance - Double Blind Treatment | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | IPX066 | Carbidopa-Levodopa | Total |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 10 | 63.4 years STANDARD_DEVIATION 8.8 | 63.2 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 8 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants | 182 Participants | 374 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 196 participants | 186 participants | 382 participants |
| Region of Enrollment Canada | 10 participants | 8 participants | 18 participants |
| Region of Enrollment France | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Germany | 12 participants | 11 participants | 23 participants |
| Region of Enrollment Poland | 34 participants | 33 participants | 67 participants |
| Region of Enrollment Romania | 3 participants | 4 participants | 7 participants |
| Region of Enrollment Spain | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Ukraine | 37 participants | 38 participants | 75 participants |
| Region of Enrollment United States | 98 participants | 93 participants | 191 participants |
| Sex: Female, Male Female | 72 Participants | 67 Participants | 139 Participants |
| Sex: Female, Male Male | 129 Participants | 125 Participants | 254 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 201 | 50 / 192 |
| serious Total, serious adverse events | 11 / 201 | 5 / 192 |
Outcome results
Primary
Percentage of Off Time During Waking Hours at End of Study
Percentage of off time during waking hours at end of study is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease).
Time frame: 22 weeks
Population: All randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | Percentage of Off Time During Waking Hours at End of Study | 23.82 percentage | Standard Deviation 14.91 |
| IR CD-LD (Active Comparator) | Percentage of Off Time During Waking Hours at End of Study | 29.79 percentage | Standard Deviation 15.81 |
p-value: <0.0001ANCOVA
Secondary
Off Time
Off time hours is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease).
Time frame: 22 weeks
Population: All randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | Off Time | 3.87 hours | Standard Deviation 2.46 |
| IR CD-LD (Active Comparator) | Off Time | 4.88 hours | Standard Deviation 2.71 |
p-value: <0.0001ANCOVA
Secondary
On Time Without Troublesome Dyskinesia
On time without troublesome dyskinesiais measured by using the Parkinson's disease diary. On time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living.
Time frame: 22 weeks
Population: All randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | On Time Without Troublesome Dyskinesia | 11.84 hours | Standard Deviation 2.96 |
| IR CD-LD (Active Comparator) | On Time Without Troublesome Dyskinesia | 10.91 hours | Standard Deviation 2.82 |