Parkinson's Disease
Conditions
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.
Interventions
DRUGIPX066
Subjects were converted from their current treatment to IPX066 over a 6-week period. Experimental Drug Product: IPX066 (carbidopa-levodopa) extended-release capsules
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Impax Laboratories, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression (PGI) | 6 months | At Part 1 Week 6, Part 2 Month 3 and Month 6 or at Early Termination, the subjects rated the change in their condition with IPX066 treatment from their condition prior to Part 1 Visit 1(Baseline) using Patient Global Impression (PGI) 7-point scale. 1=very much worse and 7=very much improved. |
| Clinical Global Impression (CGI) | 6 months | Clinician-reported satisfaction outcome of IPX066 using Clinical Global Impression (PGI) 7-point scale. At Part 1 Week 6; Part 2 Month 3, and Month 6 or at Early Termination, the Investigator rated how much a subject's overall condition had changed since Part 1 Visit 1 (Baseline) using 7-point scale. 1=very much worse and 7=very much improved. |
| Parkinson's Disease Questionnaire-8 (PDQ-8) | 6 months | Change from Baseline in Parkinson's disease Questionnaire-8 (PDQ-8) at End of Study or early discontinuation. The PDQ-8 is a self-reported questionnaire consisting of 8 questions regarding the subject's disease symptoms, each item ranging from 0 to 4, and the responses consist of 0=Never, 1=Occasionally, 2=Sometimes, 3=Often, and 4=Always or cannot do at all, total score ranging from 0 (never have problems/issues) to 32 (always have problems or cannot do at all). |
Countries
United States
Participant flow
Recruitment details
Date first subject enrolled: August 19, 2011 Date last subject completed: March 20, 2013
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Subjects converted from their previous CD-LD treatment to IPX066 over a 6-week period.
Following the successful completion of Part 1 of the study, eligible subjects could participate in Part 2, a 6-month open-label extension study.
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. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 10.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 43 | 17 / 32 | 9 / 12 | 35 / 43 |
| serious Total, serious adverse events | 1 / 43 | 5 / 32 | 3 / 12 | 9 / 43 |
Outcome results
Primary
Clinical Global Impression (CGI)
Clinician-reported satisfaction outcome of IPX066 using Clinical Global Impression (PGI) 7-point scale. At Part 1 Week 6; Part 2 Month 3, and Month 6 or at Early Termination, the Investigator rated how much a subject's overall condition had changed since Part 1 Visit 1 (Baseline) using 7-point scale. 1=very much worse and 7=very much improved.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Conversion | Clinical Global Impression (CGI) | 5.5 units on a scale | Standard Deviation 1.15 |
| Part 2: Open-Label Extension (Month 3) | Clinical Global Impression (CGI) | 5.7 units on a scale | Standard Deviation 1.08 |
| Part 2: Open-Label Extension (Month 6) | Clinical Global Impression (CGI) | 5.6 units on a scale | Standard Deviation 1.39 |
| Part 1 or 2 Early Termination | Clinical Global Impression (CGI) | 3.7 units on a scale | Standard Deviation 0.8 |
Primary
Parkinson's Disease Questionnaire-8 (PDQ-8)
Change from Baseline in Parkinson's disease Questionnaire-8 (PDQ-8) at End of Study or early discontinuation. The PDQ-8 is a self-reported questionnaire consisting of 8 questions regarding the subject's disease symptoms, each item ranging from 0 to 4, and the responses consist of 0=Never, 1=Occasionally, 2=Sometimes, 3=Often, and 4=Always or cannot do at all, total score ranging from 0 (never have problems/issues) to 32 (always have problems or cannot do at all).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Conversion | Parkinson's Disease Questionnaire-8 (PDQ-8) | 9.6 units on a scale | Standard Deviation 5.49 |
| Part 2: Open-Label Extension (Month 3) | Parkinson's Disease Questionnaire-8 (PDQ-8) | 8.1 units on a scale | Standard Deviation 4.62 |
| Part 2: Open-Label Extension (Month 6) | Parkinson's Disease Questionnaire-8 (PDQ-8) | 8.5 units on a scale | Standard Deviation 4.79 |
| Part 1 or 2 Early Termination | Parkinson's Disease Questionnaire-8 (PDQ-8) | 9.0 units on a scale | Standard Deviation 5.91 |
| Part 1 or 2 Early Termination | Parkinson's Disease Questionnaire-8 (PDQ-8) | 11.8 units on a scale | Standard Deviation 6.62 |
Primary
Patient Global Impression (PGI)
At Part 1 Week 6, Part 2 Month 3 and Month 6 or at Early Termination, the subjects rated the change in their condition with IPX066 treatment from their condition prior to Part 1 Visit 1(Baseline) using Patient Global Impression (PGI) 7-point scale. 1=very much worse and 7=very much improved.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Conversion | Patient Global Impression (PGI) | 5.2 units on a scale | Standard Deviation 1.35 |
| Part 2: Open-Label Extension (Month 3) | Patient Global Impression (PGI) | 5.4 units on a scale | Standard Deviation 1.3 |
| Part 2: Open-Label Extension (Month 6) | Patient Global Impression (PGI) | 5.3 units on a scale | Standard Deviation 1.49 |
| Part 1 or 2 Early Termination | Patient Global Impression (PGI) | 2.8 units on a scale | Standard Deviation 1.21 |