Idiopathic Parkinson's Disease
Conditions
Keywords
Parkinson's disease, Moderate to Severe Parkinson's Disease
Brief summary
This is a Phase 3, 52-week, open-label, flexible-dose, multinational, multicenter study to evaluate the safety and tolerability of istradefylline 20 or 40 mg/d in subjects with moderate to severe PD with motor fluctuations and dyskinesia on levodopa combination (levodopa/carbidopa or levodopa/benserazide) therapy plus at least one adjunctive PD medication. Subjects who completed 12 weeks of double-blind treatment and the 30-day follow-up period in Study No. 6002-014 will undergo Screening and Baseline evaluations for eligibility for the study. Eligible subjects will be treated with istradefylline at a starting dose of 20 mg/d with an option for a dose adjustment to 40 mg/d at Week 12 based on the Investigator's judgment of each subject's response and tolerability. If deemed necessary, one unscheduled dose adjustment visit between Week 2 to Week 12 is allowed in accordance with clinical judgment of the Investigator. Subjects who had a dose adjustment to 40 mg/d can have their dose decreased to 20 mg/d by the Investigator at a second unscheduled dose adjustment visit if there are tolerability issues. The istradefylline dose should remain fixed between Week 26 to Week 52. Consultation with the Sponsor's Medical Monitor is required prior to any unscheduled dose adjustment visits. A subject may discontinue from the study at any time.
Interventions
DRUGIstradefylline 20 mg or 40 mg
Istradefylline 20 or 40 mg
Sponsors
Kyowa Hakko Kirin Pharma, Inc.
Kyowa Kirin Co., Ltd.
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. Written informed consent; 2. Subjects who completed Study No. 6002-014 inclusive of the 30-day follow-up period; 3. Currently taking levodopa combination (carbidopa/levodopa or benserazide/levodopa) therapy plus at least one adjunctive PD medication; 4. Women of child-bearing potential (WOCBP) must use a reliable method of contraception and have a negative serum pregnancy test at Screening;
Exclusion criteria
1. Subjects with less than 70% treatment compliance throughout their enrollment on Study No 6002-014 and or with major protocol deviations in Study No. 6002-014 (subjects who failed to meet any of the inclusion criteria, subjects who met any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Long-term Safety and Tolerability of Oral Istradefylline (20mg or 40mg/Day [mg/d]) | From screening through to study completion, an average of 52 weeks | The number of subjects experiencing an adverse event as well as clinical laboratory tests (chemistry, haematology and urinalysis) were collected to evaluate the safety profile of istradefylline (20mg or 40mg/day \[mg/d\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | From baseline through to study completion at week 52, plus 30 days post last dose | The number and percentage of subjects showing improvement (moderate or mild) on PGI-I scores with Istradefylline 20 mg or 40 mg. Each subjects 'key symptom' (the symptom they had most trouble with) on the PGI-I was identified and evaluated at baseline and at Week 12, 26 and 52. In addition, the subject's overall condition and symptoms of fatigue, sleep and motivation to get things done were also evaluated at week 12, 26 and 52. Subjects rated each on a scale 1 to 5 for change from baseline status utilizing the following scale: 1= Moderate improvement (or greater) 2= Mild improvement, 3= No change from baseline, 4 = Mild deterioration, 5= Moderate deterioration (or greater). |
Countries
Canada, Czechia, Germany, Israel, Italy, Poland, Serbia, United States
Participant flow
Pre-assignment details
Subjects must have completed 12 weeks of double blind treatment in study 6002-014 including a 30 day follow up period. All subjects were screened for eligibility to participate in the trial. Subjects that met all the inclusion and none of the exclusion criteria were eligible for entry into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Istradefylline 20 mg or 40 mg Treatment for 52 weeks
Istradefylline 20 mg or 40 mg | 239 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Death | 5 |
| Overall Study | Non Compliance | 2 |
| Overall Study | Other | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Surgery | 2 |
| Overall Study | Withdrawal by Subject | 27 |
Baseline characteristics
| Characteristic | Istradefylline 20 mg or 40 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 116 Participants |
| Age, Categorical Between 18 and 65 years | 123 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 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 | 1 Participants |
| Race (NIH/OMB) White | 233 Participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment Czechia | 41 participants |
| Region of Enrollment Germany | 12 participants |
| Region of Enrollment Israel | 16 participants |
| Region of Enrollment Italy | 18 participants |
| Region of Enrollment Poland | 49 participants |
| Region of Enrollment Serbia | 18 participants |
| Region of Enrollment United States | 79 participants |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 239 |
| other Total, other adverse events | 91 / 239 |
| serious Total, serious adverse events | 30 / 239 |
Outcome results
Primary
Evaluation of the Long-term Safety and Tolerability of Oral Istradefylline (20mg or 40mg/Day [mg/d])
The number of subjects experiencing an adverse event as well as clinical laboratory tests (chemistry, haematology and urinalysis) were collected to evaluate the safety profile of istradefylline (20mg or 40mg/day \[mg/d\]).
Time frame: From screening through to study completion, an average of 52 weeks
Population: All participants who received at least one dose of assigned study drug (even a partial dose) made up the Safety Analysis Set.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Safety Analysis Set | Evaluation of the Long-term Safety and Tolerability of Oral Istradefylline (20mg or 40mg/Day [mg/d]) | Number of participants with any TEAE | 141 Participants |
| Safety Analysis Set | Evaluation of the Long-term Safety and Tolerability of Oral Istradefylline (20mg or 40mg/Day [mg/d]) | Number of participants who did'nt have any TEAE | 98 Participants |
Secondary
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set).
The number and percentage of subjects showing improvement (moderate or mild) on PGI-I scores with Istradefylline 20 mg or 40 mg. Each subjects 'key symptom' (the symptom they had most trouble with) on the PGI-I was identified and evaluated at baseline and at Week 12, 26 and 52. In addition, the subject's overall condition and symptoms of fatigue, sleep and motivation to get things done were also evaluated at week 12, 26 and 52. Subjects rated each on a scale 1 to 5 for change from baseline status utilizing the following scale: 1= Moderate improvement (or greater) 2= Mild improvement, 3= No change from baseline, 4 = Mild deterioration, 5= Moderate deterioration (or greater).
Time frame: From baseline through to study completion at week 52, plus 30 days post last dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Safety Analysis Set | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Motivation to get things done | 64 Participants |
| Safety Analysis Set | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Sleep | 48 Participants |
| Safety Analysis Set | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Overall Condition | 115 Participants |
| Safety Analysis Set | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Fatigue | 68 Participants |
| Safety Analysis Set | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Key Symtom | 97 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 26. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Sleep | 61 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 26. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Overall Condition | 109 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 26. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Fatigue | 62 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 26. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Motivation to get things done | 66 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 26. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Key Symtom | 95 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 52. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Key Symtom | 73 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 52. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Motivation to get things done | 45 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 52. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Overall Condition | 76 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 52. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Sleep | 37 Participants |
| Efficacy Analysis Based on PGI-I Scores at Week 52. | Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). | Fatigue | 40 Participants |