A Phase Ib Trial of Combined Febuxostat and Inosine Therapy in Patients With Parkinson's Disease

Overview

This study will test the safety of twice-daily oral dosing of combined febuxostat and inosine in 24 patients with Parkinson's disease. Participants will receive one of the four regimens, taken twice daily for 12 weeks: Who can join: Adults with early-stage Parkinson's disease on stable medication regimens. What participants do: * Take their assigned dose twice daily (morning and evening) for 12 weeks. * Visit the clinic at baseline and weeks 4, 8, and 12 for blood tests (including hypoxanthine), exams, and questionnaires. * Keep a simple diary of any side effects or changes in daily activities. Risks and benefits: Possible side effects include mild gastrointestinal upset, headache, or elevated uric acid levels. While direct benefit is not guaranteed, this safety data will inform future Parkinson's disease treatments. Learn more: Contact \[site-specific contact info\] for details on eligibility and enrollment.

Interventions

• Drug Febuxostat
  Febuxostat tablets (per randomized assignment), administered orally twice daily (once in the morning and once in the evening) for 12 weeks.
• Drug Inosine
  Inosine tablets (per randomized assignment), administered orally twice daily (once in the morning and once in the evening) for 12 weeks.

Primary outcome measures

• Change in plasma hypoxanthine concentration from baseline to Week 12 [Time frame: 12 weeks]

Secondary outcome measures (5)

• Change in plasma hypoxanthine concentration from baseline to Week 4 [Time frame: 4 weeks]
• Change in cerebrospinal fluid (CSF) hypoxanthine concentration from baseline to Week 12 [Time frame: 12 weeks]
• Change in MDS-UPDRS Part III score from baseline to Week 12 [Time frame: 12 weeks]
• Change in Mini-Mental State Examination (MMSE) score from baseline to Week 12 [Time frame: 12 weeks]
• Change in Geriatric Depression Scale-15 (GDS-15) score from baseline to Week 12 [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• Able to provide voluntary written informed consent.
• Receiving stable Parkinson's disease medication (no changes in type or dose) for at least 3 months before enrollment.
• Age 18 to 80 years at the time of consent.
• Diagnosed with Parkinson's disease by a specialist according to MDS-PD diagnostic criteria, and at pre-enrollment screening, all of the following are met:

• Hoehn-Yahr stage (ON state) 1 to 3
• MDS-UPDRS Part III (ON state) score 10 to 35
• Mini-Mental State Examination (MMSE) score ≥ 24

Exclusion criteria

• Requires almost total assistance in daily life and is unable to walk or stand unaided.
• Currently taking azathioprine, mercaptopurine hydrate, vidarabine, didanosine, or rosuvastatin.
• Used febuxostat, allopurinol, or topiroxostat within 3 months before study start.
• Taking any supplement containing inosine.
• Started any new Parkinson's disease medication or therapy within 3 months before enrollment.
• Serum creatinine >1.5× upper limit of normal (ULN), or AST (GOT) or ALT (GPT) >2× ULN at screening.
• History of surgical treatment for Parkinson's disease.
• History of or comorbid hypersensitivity/allergy to any ingredient of the investigational drugs.
• Participation in another clinical trial involving an unapproved drug within 30 days before consent, or currently enrolled in another interventional study.
• Pregnant or breastfeeding, or unwilling/unable to use reliable contraception during the study period.
• Positive test at screening for HIV, HBV, HTLV-1, or syphilis; \*\*HCV antibody-positive with undetectable HCV RNA\*\* is allowed.
• Unable to take the investigational drugs orally without changing the dosage form.
• Gastrointestinal disease or prior GI surgery that may affect drug absorption, as judged by the investigator.
• Psychiatric disorder or symptoms that interfere with daily life and make study participation difficult.
• Unable to complete assessments or questionnaires independently.
• Any other condition that, in the investigator's judgment, would make participation unsafe or inappropriate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 1 center

• Fujita Health University — Toyoake

Publications

• Kamatani N, Hashimoto M, Sakurai K, Gokita K, Yoshihara J, Sekine M, Mochii M, Fukuuchi T, Yamaoka N, Kaneko K. Clinical studies on changes in purine compounds in blood and urine by the simultaneous administration of febuxostat and inosine, or by single administration of each. Gout and Nucleic Acid Metabolism. 2017;41 (2): 171-181.
• Kamatani N, Kushiyama A, Toyo-Oka L, Toyo-Oka T. Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that enhances cellular ATP. J Hum Genet. 2019 Apr;64(4):351-353. doi: 10.1038/s10038-018-0558-0. Epub 2019 Jan 10. PMID 30631120
• Johnson TA, Jinnah HA, Kamatani N. Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP. Front Pharmacol. 2019 Feb 19;10:98. doi: 10.3389/fphar.2019.00098. eCollection 2019. PMID 30837873
• Shima S, Mizutani Y, Yoshimoto J, Maeda Y, Ohdake R, Nagao R, Maeda T, Higashi A, Ueda A, Ito M, Mutoh T, Watanabe H. Uric acid and alterations of purine recycling disorders in Parkinson's disease: a cross-sectional study. NPJ Parkinsons Dis. 2024 Sep 9;10(1):170. doi: 10.1038/s41531-024-00785-0. PMID 39251680
• Watanabe H, Hattori T, Kume A, Misu K, Ito T, Koike Y, Johnson TA, Kamitsuji S, Kamatani N, Sobue G. Improved Parkinsons disease motor score in a single-arm open-label trial of febuxostat and inosine. Medicine (Baltimore). 2020 Aug 28;99(35):e21576. doi: 10.1097/MD.0000000000021576. PMID 32871874

Identifiers

NCT: NCT07170475 · FU-PD-i01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗