臨床研究等提出・公開システム

Intervention Study for the effect of Istradefylline on onset of Dyskinesia in Patients with Parkinson's Disease (ODYSSEI Study)

ODYSSEI Study (ODYSSEI Study)

212

Among 250 subjects who gave consent to participate in this study, 214 were enrolled in the study, 105 were assigned to the Istradefylline treatment group (hereinafter referred to as the Treatment Group), and 109 were assigned to the Istradefylline non-treatment group (hereinafter referred to as the Non-treatment Group). Among 214 subjects enrolled in this study, 104 subjects in the Treatment Group and 108 subjects in the Non-treatment Group (212 subjects in total) were included in the safety analysis set, and 103 subjects in the Treatment Group and 107 subjects in the Non-treatment Group (210 subjects in total) were included in the efficacy analysis set. In the efficacy analysis set, the proportion of subjects receiving a concomitant dopamine agonist was slightly higher in the Non-treatment Group and that of subjects receiving a concomitant Zonisamide was slightly higher in the Treatment Group; however, there were no major differences between the two groups in terms of gender, age, duration of Parkinson disease, daily levodopa dose, and modified Hoehn & Yahr scale, etc.

This study started enrollment in October 2016, the first subject was enrolled in March 2017, and observation of all subjects was completed in April 2022. Among 250 subjects who gave consent to participate in the study, 214 subjects, excluding 36 screen failures, were enrolled in the study, and 105 subjects were assigned to the Treatment Group and 109 subjects were assigned to the Non-treatment Group. There were one subject each in the Treatment Group and Non-treatment Group who discontinued before the start of protocol treatment, 42 and 35 subjects who discontinued after the start of protocol treatment, respectively, and 62 and 73 subjects who completed the study, respectively.

In the safety analysis set of 212 subjects (104 subjects in the Treatment Group; 108 subjects in the Non-treatment Group), 376 adverse events occurred in 90 subjects (86.5%) in the Treatment Group and 473 occurred in 99 subjects (91.7%) in the Non-treatment Group. Of these, regarding adverse events classified according to PT, the incidence of nasopharyngitis was significantly higher in the Treatment Group and the incidence of influenza was significantly higher in the Non-treatment Group. Regarding adverse events classified according to SOC, respiratory, thoracic, and mediastinal disorders was significantly higher in the Non-treatment Group. However, there were no significant differences in the incidence of adverse events related to the protocol treatment between the two groups. A total of 33 serious adverse events occurred in 21 subjects (20.2%) in the Treatment Group and 51 occurred in 31 subjects (28.7%) in the Non-treatment Group. None of these events were related to the protocol treatment.

1) Primary Outcome Dyskinesia occurred in 39 subjects (37.9%) in the Treatment Group and 44 (41.1%) in the Non-treatment Group. Median disease-free survival for dyskinesia was 1100 days in the Treatment Group (lower 95% confidence limit: 924 days) and 1082 days in the Non-treatment Group (lower 95% confidence limit: 820 days), with no significant differences between the two groups. The subgroup analysis showed that the time to onset of dyskinesia was longer in the Treatment Group than in the Non-treatment Group for subjects of the median age (68 years) or older, and longer in the Non-treatment Group than in the Treatment Group for subjects who were under the median age and subjects whose age at onset of Parkinson disease was under 60 years old. 2) Secondary Outcomes There were no significant differences between the two groups in time to onset of troublesome dyskinesia, total scores of MDS-UPDRS Part I, II, III, and IV, PDQ-39 SI, modified Hoehn & Yahr scale (On/Off), and MMSE score. Levodopa daily dose was not significantly different between the two groups; however, Levodopa equivalent daily dose was significantly lower in the Treatment Group than in the Non-treatment Group.

There was no significant difference in the time to onset of dyskinesia between treatment with and without Istradefylline in subjects with Parkinson disease who had wearing-off. Levodopa equivalent daily dose was significantly lower in the Treatment Group than in the Non-treatment Group, but there were no differences in other efficacy outcomes and protocol treatment-related adverse events. There were no protocol treatment-related serious adverse events in both groups.

July. 01, 2024

No

Not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs071180014

Tsuboi Yoshio

Fukuoka University Hospital

7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

tsuboi@cis.fukuoka-u.ac.jp

Tsuboi Yoshio

Fukuoka University Hospital

7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

+81-92-801-1011

tsuboi@cis.fukuoka-u.ac.jp

Complete

Oct. 01, 2016

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Current use of levodopa-containing drugs more than 300mg/day administered at least three times daily
2) Patients with wearing-off
3) Patients who have never previously experienced dyskinesia
4) >= 30 to < 80 years of age at the time of consent.
5) Diagnosed as Parkinson's disease based on UK Parkinson's Disease Society Brain Bank criteria
6) Stages <=4 in the ON state for Modified Hoehn and Yahr Scale.
7) Stable antiparkinson drug regimen for at least 4 weeks prior to study entry.
8) Completion of patient diary training and able to satisfactorily complete patient diary.
9) Patients who have given written consent if the patient has difficulty in writing due to his or her condition, a representative may sign the written consent, subject to the patient's prior oral consent

1) Current use of Istradefylline (within 1 year prior to study entry)
2) Current use of amantadine (within 3 months prior to study entry)
3) Current use of an investigational drug (within 4 months prior to study entry.)
4) Patients with dementia or a score of 23 or less on the Mini-Mental State Examination (MMSE)
5) Patients with a previous history of brain surgery for the treatment of parkinson's disease.
6) Current use or plan to administer levodopa/carbidopa intestinal gel
7) Patients with moderate to severe hepatic disorder
8) Current use of a strong inhibitor of CYP3A4 (within 14days prior to study entry)
9) Current use of typical and atypical antipsychotics (within 3 months prior to study entry)
10) Female patients who are pregnant, trying to become pregnant or nursing (lactating) an infant.
11) Patients who are in the Investigator's judgment unlikely to comply with medical regimens or study requirements.

Both

Parkinson's disease

Arm A: Treatment with Istradefylline combined with optimal medical therapy.
Treatment with Istradefylline will be started at a dose of 20 mg administered once daily at Week 0. The dose of Istradefylline will be increased to 40 mg once daily if the patient has no tolerability issues and still has motor symptoms at Week 4.
From the following day of Week 4, Optimal medical therapy including Istradefylline will be applied to each patient.

Arm B: Optimal medical therapy without Istradefylline.
Treatment with increased dose of previously used antiparkinson drugs or addition of new antiparkinson drug other than Istradefylline will be started at Week 0.
After Week 4, Optimal medical therapy without Istradefylline will be applied to each patient.

Parkinson's disease

Time to onset of dyskinesia

-Time to onset of troublesome dyskinesia
-Change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part1,2,3,4 score and total score
-Change in Parkinson's Disease Questionnaire (PDQ)-39 score
-Change in modified Hoehn & Yahr scale
-Change in Mini Mental State Examination (MMSE) score
-Change in Levodopa dose and Levodopa equivalent dose

+81-92-643-7171

Oct. 31, 2018

N A