Non-inferiority study of zonisamide versus levodopa preparations in DLB parkinsonism

JRCT ID: jRCTs051200054

Registered date:08/09/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Parkinsonism with Dementia with Lewy bodies
• Date of first enrollment: 22/04/2021
• Target sample size: 130
• Study type: Interventional

Intervention(s)

1) Zonisamide + levodopa group: DLB patients receiving levodopa treatment at 300 mg/day or lower will be given one tablet of the investigational drug (zonisamide tablet 25 mg) orally once daily (morning) for 24 weeks.
2) Increased levodopa dose group: DLB patients receiving levodopa treatment at 300 mg/day or lower will be given another levodopa preparation at 100 mg/day for 24 weeks.
Dose modification, interruption, or discontinuation of levodopa preparations other than the study drug is prohibited from the start of the observation period (Visit 1) until the end of the evaluation period (Visit 6).

Outcome(s)

• Primary Outcome: - Change in the MDS-UPDRS Part III total score at Week 24

Secondary Outcome

- MDS-UPDRS Part III total score, individual item scores, and their changes at each timepoint
- MDS-UPDRS Part II total score, individual item scores, and their changes at each timepoint
- Neuropsychiatric inventory (NPI)-12 total score, NPI-10 total score, individual item scores, and their changes at each timepoint
- Numbers of correct responses, illusory responses, and other responses on the pareidolia test, and their changes at each timepoint
- MMSE total score, individual item scores, and their changes at each timepoint
- Total score on the Japanese version of REM sleep behavior disorder questionnaire (RBDQ-JP), individual item scores, and their changes at each timepoint
- Eating Questionnaire total score, individual item scores, and their changes at each timepoint
- Quality of life (QOL) score as measured by the EQ-5D-5L questionnaire and its change at each timepoint
- Zarit Caregiver Burden Interview (ZBI) total score, individual item scores, and their changes at each timepoint
- Fall risk total score, individual item scores, their changes, any bone fracture, and any surgical treatment for fall-related injuries at each timepoint
- Occurrence of event:
- Time to first fall and time to first bone fracture
- Adverse events
- Study withdrawal
- Study withdrawal because of the need for managing aggravated behavioral and psychological symptoms of dementia (BPSD)

Key inclusion & exclusion criteria

• Age minimum: >= 50age old
• Age maximum: < 90age old
• Gender: Both

Include criteria

At the start of the observation period (Visit 1) and before the start of the evaluation period (Visit 2), patients with dementia with Lewy bodies (DLB) parkinsonism who are receiving levodopa treatment at 300 mg/day or lower and still have Parkinsonism which requires further treatment, are eligible for this study if they meet all of the following criteria.
1) Written voluntary informed consent is obtained from the patient and legal representative after a full explanation and understanding of the objectives and nature of this study, expected efficacy/pharmacological action, risk, and other information*
- In principle, consent from the patient is required, but if it is difficult to obtain the consent from the patient who is objectively judged to lack the ability of giving informed consent, etc., assent is obtained from the patient with written consent of legal representative.
2) Diagnosed with probable DLB according to the revised criteria for clinical diagnosis of DLB (among the core clinical features, onset of "parkinsonism" is essential)*
3) Aged 50 years or older and younger than 90 years at the time of informed consent*
4) Outpatients
5) (Possibly have remained Parkinsonism which requires further treatment) A total score of 20 or higher on Part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
6) Their caregivers meeting all of the following criteria*
- Witten agreement to cooperate with this study is obtained
- Able to provide patient information and drug management required for this study (the caregiver may live together with the patient or separately)
- Able to accompany the patient to site visits throughout the study
7) Continuously taking levodopa preparations initiated at or before the start of the observation period (Visit 1), on a stable dose of 300 or lower mg/day throughout the observation period**
8) History of hallucination or delusion
- Including hallucination or delusion present at eligibility assessment
9) A stable dose of any antidementia drug, if being used, throughout the observation period**
10) Use of the following drugs (restricted concomitant drugs) on a stable dose from 2 weeks before the start of the study treatment (Day 1)**
- Other drugs that might affect evaluation (e.g., antihypertensives, central nervous system agents, cardiovascular agents, digestive organ agents, and traditional Chinese medicines)
*: Matters only to be checked at the start of the observation period (Visit 1)
**: Matters only to be checked before the start of the evaluation period (Visit 2)

Exclude criteria

Patients who meet any of the following criteria are excluded from this study.
1) Patients with non-DLB parkinsonism (e.g., drug - induced parkinsonism)
2) Patients with Parkinson's disease associated with dementia (Parkinson's disease dementia[ PDD]patients)
PDD patients: those with parkinsonism occurring 1 year or longer before onset of dementia
3) A total score of less than 10 on the Mini-mental State Examination (MMSE)
4) Concomitant epilepsy
5) Taking any antiparkinsonian drug (including Stalevo [levodopa/carbidopa hydrate/entacapone] and droxidopa) other than levodopa preparations
6) Taking any benzamide antipsychotic (sulpiride, sultopride, tiapride, or nemonapride)
7) Taking any non-quetiapine antipsychotic
8) Taking any metoclopramide preparation
9) Taking nicergoline
10) Previous intake of zonisamide
11) Previous surgical treatment for parkinsonism such as stereotaxy
12) Ineligible for this study in the opinion of the investigator because of severe phychiatric symptoms such as confusion, hallucination, delusion, and abnormal behaviors
13) Any serious concomitant disease which qualifies as Grade 3 as defined by the Criteria for Seriousness Classification of Adverse Drug Reactions*
14) History of any serious liver disease which qualifies as Grade 3 as defined by the Criteria for Seriousness Classification of Adverse Drug Reactions
15) History of malignant syndrome
16) Concomitant cancer or history of cancer within 5 years before the start of this study
17) Pregnant women, patients who may possibly be pregnant, patients who may become pregnant by themselves or their partners without using proper contraceptive measures, patients who plan to become pregnant (including providing sperm to a third party or freezing sperm etc.) or lactating mothers
18) Planned participation during the observation period of this study or concomitant participation in another clinical study, post-marketing clinical study, or any other interventional clinical research
19) Otherwise ineligible for this study in the opinion of the investigator or subinvestigator
* Grade 3 as defined by the Criteria for Seriousness Classification of Adverse Drug Reactions: adverse drug reaction considered serious, which may be fatal or has the risk of causing permanent dysfunction that hinders daily living depending on the patient's predisposition or condition when the event is observed.

Related Information

• Primary Sponsor: Ikeda Manabu
• Source(s) of Monetary Support: Sumitomo Pharma Co., Ltd.