A 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson's Disease (KW-6002)
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| ClinicalTrials.gov Identifier: NCT01968031 |
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Recruitment Status :
Completed
First Posted : October 23, 2013
Results First Posted : November 20, 2020
Last Update Posted : November 20, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Idiopathic Parkinson's Disease | Drug: Istradefylline 40 mg Drug: Istradefylline 20 mg Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 613 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, 12-week, Double-Blind, Placebo-Controlled, Randomized, Multicenter Study to Evaluate the Efficacy of Oral Istradefylline 20 and 40 mg/Day as Treatment for Subjects With Moderate to Severe Parkinson's Disease |
| Study Start Date : | October 2013 |
| Actual Primary Completion Date : | October 2016 |
| Actual Study Completion Date : | October 2016 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Istradefylline 20 mg/day
Istradefylline 20 mg and placebo to match istradefylline 40 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks. |
Drug: Istradefylline 20 mg
Istradefylline 20 mg and placebo
Other Name: KW-6002 Drug: Placebo Placebo |
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Experimental: Istradefylline 40 mg/day
Istradefylline 40 mg and placebo to match istradefylline 20 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks. |
Drug: Istradefylline 40 mg
Istradefylline 40 mg and placebo
Other Name: KW-6002 Drug: Placebo Placebo |
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Placebo Comparator: Placebo
Placebo to match istradefylline 20 mg and placebo to match istradefylline 40 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks. |
Drug: Placebo
Placebo |
- Change From Baseline in the Total Hours of Awake Time/Day Spent in the OFF State at Week 12 [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]Based on the 24-hour ON/OFF patient diary data.
- Total Hours of ON Time Per Day Without Troublesome Dyskinesia [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]Based on Patient's ON/OFF Diary
- Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Part III); [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part III assesses the motor signs of Parkinson's Disease with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part III is 0 to 68. The lower the score, the more favorable the response.
- Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) Score (Part II) [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part II is a self-evaluation of the activities of daily life (ADL) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part II is 0 to 52. The lower the score, the more favorable the response.
- Unified Parkinson's Disease Rating Scale (UPDRS Mentation, Behaviour) and Mood (Part I) [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part I is the evaluation of mentation, behavior, and mood with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part I is 0 to 16. The lower the score, the more favorable the response.
- Total UPDRS (Parts I + II + III); [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total possible score range for all parts combined is 0 to 136. The lower the score, the more favorable the response.
- Patient Global Impression - Improvement (PGI-I) Scale [ Time Frame: Baseline, Week 2, Week 6, Week 10, Week 12 and 30-day FU visit ]
The "key symptom" on the PGI-I was evaluated at baseline and subsequent post-baseline visits for the subject's overall condition and the symptoms of fatigue, sleep, motivation to get things done, and each subject's key symptom. Subjects rated each on a scale of 1 to 5 for change from baseline 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)
A lower number is a better outcome. Overall condition is presented below.
- Sleep Time in Hours Per Day Based Upon 24-hour Diaries. [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]
- Percentage of Awake Time Per Day Spent in the OFF State [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]
- Percentage of ON Time Per Day Without Troublesome Dyskinesia. [ Time Frame: Baseline, Week 2, Week 6, Week 10 and Week 12. ]
- Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline and Week 12. ]
The Montreal Cognitive Assessment (MoCA) assesses different cognitive domains, broken down as follows:
Visuospatial and executive functioning: 5 points Animal Naming: 3 points Attention: 6 points Language: 3 points Abstraction: 2 points Delayed recall (short-term memory): 5 points Orientation: 6 points
Scores can range from 0 to 30. A score of 26 or above is considered normal.
- Beck Depression Inventory (BDI) [ Time Frame: Baseline and Week 12. ]
The Beck Depression Inventory is a 21-question test that measures the severity of depression. Subjects rated each on a scale of 0 to 3 for change from baseline utilizing the following scale:
- 0 = I do not feel sad
- 1 = I feel sad
- 2 = I am sad all the time and I can't snap out of it
- 3 = I am so sad or unhappy that I can't stand it
The test is scored for each question using the above scale to determine the severity of depression. Scoring is as shown below:
- 0 to 9: minimal depression
- 10 to 18: mild depression
- 19 to 29: moderate depression
- 30 to 63: severe depression
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| Ages Eligible for Study: | 30 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 30 years of age or older.
- UK Parkinson's Disease Society (UKPDS) brain bank criteria (Step 1 and 2) for PD
- PD Stages 2-4 in the ON state for Modified Hoehn and Yahr Scale.
- On levodopa therapy for at least 1 year with beneficial clinical response at the baseline visit
- Taking at least 400mg levodopa combination daily and on stable regimen of any other anti-Parkinsonian drugs (MAO-B, COMT, DA) for at least 2 weeks prior to randomization
- Stable dopaminergic regimen for at least 4 weeks immediately prior to randomization
- Documented end-of-dose wearing-off and levodopa-induced dyskinesia
- Have an average of two hours of OFF time per day
Exclusion Criteria:
- Subjects on apomorphine and/or dopamine receptor antagonists or direct gastrointestinal levodopa infusion.
- Subject who have had neurosurgical operation for PD
- Subjects taking A2a antagonist, potent CYP3A4 inhibitors, potent CYP34A inducers
- Subjects who smoke > 5 cigarettes/day
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968031
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| Study Chair: | Kyowa Hakko Kirin Pharma, Inc. | Kyowa Hakko Kirin Pharma, Inc. |
| Responsible Party: | Kyowa Hakko Kirin Pharma, Inc. |
| ClinicalTrials.gov Identifier: | NCT01968031 |
| Other Study ID Numbers: |
6002-014 2013-002254-70 ( EudraCT Number ) |
| First Posted: | October 23, 2013 Key Record Dates |
| Results First Posted: | November 20, 2020 |
| Last Update Posted: | November 20, 2020 |
| Last Verified: | September 2020 |
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Parkinson's disease Moderate to Severe Parkinson's Disease |
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Istradefylline Parkinson Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Movement Disorders Synucleinopathies |
Neurodegenerative Diseases Adenosine A2 Receptor Antagonists Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |