Trial Outcomes & Findings for Long Term Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease (NCT NCT02610231)

Last Updated: 2024-04-25

Results Overview

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 \[mg/d\]).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

239 participants

Primary outcome timeframe

From screening through to study completion, an average of 52 weeks

Results posted on

2024-04-25

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Istradefylline 20 mg or 40mg Eligible subjects were treated with istradefylline at a starting dose of 20mg/d with an option for dose adjustment at week 40mg/d at week 12 based on the Investigator's judgement of each subject's response and tolerability. If deemed necessary, one unscheduled dose adjustment visit between weeks 2 and 12 was allowed in accordance with the Investigator's clinical judgement. Subjects who had a dose adjustment to 40 mg/d could have their dose decreased to 20mg/d by the investigator at a second unscheduled dose adjustment visit if there were tolerability issues. The istradefylline dose was to remain fixed between Weeks 26 and weeks 52. Subjects took one tablet orally in the morning
Overall Study STARTED	239
Overall Study COMPLETED	179
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Istradefylline 20 mg or 40mg Eligible subjects were treated with istradefylline at a starting dose of 20mg/d with an option for dose adjustment at week 40mg/d at week 12 based on the Investigator's judgement of each subject's response and tolerability. If deemed necessary, one unscheduled dose adjustment visit between weeks 2 and 12 was allowed in accordance with the Investigator's clinical judgement. Subjects who had a dose adjustment to 40 mg/d could have their dose decreased to 20mg/d by the investigator at a second unscheduled dose adjustment visit if there were tolerability issues. The istradefylline dose was to remain fixed between Weeks 26 and weeks 52. Subjects took one tablet orally in the morning
Overall Study Withdrawal by Subject	27
Overall Study Adverse Event	20
Overall Study Death	5
Overall Study Surgery	2
Overall Study Physician Decision	1
Overall Study Non Compliance	2
Overall Study Other	3

Baseline Characteristics

Long Term Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Istradefylline 20 mg or 40 mg n=239 Participants Treatment for 52 weeks Istradefylline 20 mg or 40 mg
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	123 Participants n=5 Participants
Age, Categorical >=65 years	116 Participants n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants
Sex: Female, Male Male	152 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	233 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants
Region of Enrollment United States	79 participants n=5 Participants
Region of Enrollment Czechia	41 participants n=5 Participants
Region of Enrollment Poland	49 participants n=5 Participants
Region of Enrollment Italy	18 participants n=5 Participants
Region of Enrollment Israel	16 participants n=5 Participants
Region of Enrollment Serbia	18 participants n=5 Participants
Region of Enrollment Germany	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Safety Analysis Set n=239 Participants Open label treatment for 52 weeks with Istradefylline 20 mg or 40 mg	Efficacy Analysis Based on PGI-I Scores at Week 26. The percentage of subjects showing improvement (moderate or mild) on PGI-I scores at (week 26).	Efficacy Analysis Based on PGI-I Scores at Week 52. The percentage of subjects showing improvement (moderate or mild) on PGI-I scores at (week 52).
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	—	—
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 outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Safety Analysis Set n=237 Participants Open label treatment for 52 weeks with Istradefylline 20 mg or 40 mg	Efficacy Analysis Based on PGI-I Scores at Week 26. n=214 Participants The percentage of subjects showing improvement (moderate or mild) on PGI-I scores at (week 26).	Efficacy Analysis Based on PGI-I Scores at Week 52. n=187 Participants The percentage of subjects showing improvement (moderate or mild) on PGI-I scores at (week 52).
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). Fatigue	68 Participants	62 Participants	40 Participants
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). Sleep	48 Participants	61 Participants	37 Participants
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). Motivation to get things done	64 Participants	66 Participants	45 Participants
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). Overall Condition	115 Participants	109 Participants	76 Participants
Patient Global Impression - Overall Condition (Improvement by Study Visit) (ITT Analysis Set). Key Symtom	97 Participants	95 Participants	73 Participants

Adverse Events

Istradefylline 20 mg or 40 mg

Serious events: 30 serious events

Other events: 91 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Istradefylline 20 mg or 40 mg n=239 participants at risk Treatment for 52 weeks Istradefylline 20 mg or 40 mg
Vascular disorders Circulatory Collapse	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
General disorders Asthenia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Psychiatric disorders Panic Attack	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Psychiatric disorders Confusional state	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Limb Traumatic Amputation	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Procedure Pain	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Pubis Fracture	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Incorrect dose Administered	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Fall	1.3% 3/239 • Number of events 3 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Injury, poisoning and procedural complications Femur Fracture	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Investigations Protein Total Decrease	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Investigations Blood Creatinine Increased	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Coronary Artery Disease	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Cardiac Arrest	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Atrial Fibrillation	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Atrioventricular block complete	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Cardiac Failure Congestive	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Bradycardia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Angina Pectoris	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Cardiac disorders Cardiac failure	0.42% 1/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Blood and lymphatic system disorders Anaemia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute Respiratory failure	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders On and Off Phenomenon	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Syncope	0.42% 1/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Parkinson's Disease	1.3% 3/239 • Number of events 3 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Convulsion	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Transcient Ischaemic attack	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Cerebrovascular accident	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Sciatica	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Multiple Sclerosis	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Carotid artery stenosis	0.42% 1/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Dyskinesia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Eye disorders Glaucoma	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Eye disorders Diplopia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Gastrointestinal disorders Gastritis erosive	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Renal and urinary disorders Urinary Retention	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Hepatobiliary disorders Drug-induced liver injury	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Urinary Tract Infection	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Bronchitis	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Pneumonia	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Sepsis	0.84% 2/239 • Number of events 2 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Gas Gangrene	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Infections and infestations Necrotising fasciitis	0.42% 1/239 • Number of events 1 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.

Other adverse events

Other adverse events
Measure	Istradefylline 20 mg or 40 mg n=239 participants at risk Treatment for 52 weeks Istradefylline 20 mg or 40 mg
Nervous system disorders Dyskinesia	18.0% 43/239 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Fall	12.1% 29/239 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.
Nervous system disorders Parkinson's disease	7.9% 19/239 • Adverse Events were monitored and collected for up to 52 weeks from the time subjects signed the ICF and for 30 days after their last dose of study drug.

Additional Information

Development Devision - Project Management Department

Kyowa Kirin

Phone: 609-919-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER