Safety, Tolerability and Symptomatic Efficacy of the ROCK-Inhibitor Fasudil in Patients With Parkinson's Disease

NCT ID: NCT05931575

Last Updated: 2023-09-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-11
• Study Completion Date: 2024-09-30

Brief Summary

The aim of this phase Ila trial is to provide evidence on safety, tolerability and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with early Parkinson's disease (PD). Fasudil has shown neuroprotective and pro-regenerative effects, modulated microglial activity and attenuated alpha-synuclein aggregation in PD models in vitro and in vivo. It has been licensed in Japan since 1995 for the treatment of vasospasms and has a beneficial safety profile arguing for its repurposing. Up to 15 trial centers in Germany will recruit patients. Blinded trial medication will be prepared and shipped by the University Pharmacy Leipzig. Fasudil in two dosages or placebo will be administered orally twice daily to 75 early PD patients for a total of 3 weeks. Safety, tolerability and symptomatic efficacy endpoints will be assessed up to 4 weeks after end of treatment. Its well-known safety profile and the lack of disease-modifying treatments for PD justifies its use in patients with early Parkinson's disease. ROCK-PD is a prerequisite for subsequent long-term clinical trials assessing disease-modification in PD in addition to symptomatic efficacy.

Conditions

Idiopathic Parkinson´s Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

intervention arm (low dose)

oral Fasudil solution 88 mg/day (2 x 44 mg)

Group Type: EXPERIMENTAL

Fasudil hydrochloride

Intervention Type: DRUG

Duration of intervention per patient: 22 days; Application scheme: one dose on day 1, two doses on days 2 - 21, one dose on day 22.

intervention arm (high dose)

oral Fasudil solution 44 mg/day (2 x 22 mg)

Group Type: EXPERIMENTAL

Fasudil hydrochloride

Intervention Type: DRUG

Duration of intervention per patient: 22 days; Application scheme: one dose on day 1, two doses on days 2 - 21, one dose on day 22.

Control intervention arm (placebo)

oral placebo solution 2x/day.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.05 ml Quinine dihydrochloride solution (from Quinina Labesfal) in screw flask supplemented with 30 ml Glucose 40% solution from miniplasco directly before use

Interventions

Fasudil hydrochloride

Duration of intervention per patient: 22 days; Application scheme: one dose on day 1, two doses on days 2 - 21, one dose on day 22.

Intervention Type: DRUG

Placebo

0.05 ml Quinine dihydrochloride solution (from Quinina Labesfal) in screw flask supplemented with 30 ml Glucose 40% solution from miniplasco directly before use

Intervention Type: DRUG

Other Intervention Names

Fasudil hydrochloride (Fasudil); Quinine dihydrochloride solution

Eligibility Criteria

Inclusion Criteria

1. Patients with a diagnosis of at least probable PD according to MDS criteria (Postuma et al. MovDis 2015) and

2. Hoehn & Yahr stage 1 - 3

3. must be non-fluctuating (no wearing-off, no dyskinesia) and stable on symptomatic PD medication for at least 6 weeks

4. age: 30 - 80 years

5. Women of childbearing potential must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are for example implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner

6. Capable of thoroughly understanding all information given and giving full informed consent according to GCP

Exclusion Criteria

1. Atypical, secondary Parkinsonian syndromes, PD mimics, or any other medical condition known to have an association with Parkinsonian syndromes, which might confound or obscure the diagnosis of PD

2. Patients with a history of intracranial bleeding, known intracerebral aneurysms or Moyamoya disease, or positive family history for the above. If only family history positive, MR- or x-ray-based cranial imaging not older than 24 months must confirm absence of bleeding, aneurysms, or Moyamoya

3. Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment

4. Patients with known arterial hypotension (resting blood pressure <90/60 mmHg) or previous hypotensive episodes or requiring treatment for increasing of blood pressure, such as fludrocortisone, midodrine, etilefrine, cafedrine, or theodrenaline

5. Patients with an uncontrollable or unstable arterial hypertensive disease (resting blood pressure >180 mmHg systolic and/or >120 mmHg diastolic under current antihypertensive medication)

6. Known pulmonary hypertension and any medication prescribed for treatment of pulmonary hypertension

7. Confirmed hepatic insufficiency or abnormal liver function (stable ASAT and/or ALAT greater than 3 times the upper limit of the normal range) and determined to be non-transient through repeat testing

8. Renal insufficiency with a glomerular filtration rate (GFR) <60 ml/min/1,73m² (calculated by MDRD equation or byCKD-EPI equation) and determined to be non-transient through repeat testing

9. Major psychiatric disorder, significant cognitive impairment or clinically evident dementia precluding evaluation of symptoms

10. Hypersensitivity to any component of the IMP

11. Liable to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of emergency

12. Pregnant or breast-feeding females or females with childbearing potential, if no adequate contraceptive measures are used

13. Previous participation in another clinical study involving trial medication within the preceding 12 weeks or five terminal half times of the longest to be eliminated trial medications (whichever is longer) or previous participation in this trial

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Lingor, MD

Role: PRINCIPAL_INVESTIGATOR

Technische Universität München, Klinikum rechts der Isar, Klinik und Poliklinik für Neurologie

Locations

Technische Universität München, Klinikum rechts der Isar, Klinik und Poliklinik für Neurologie

Munich, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Paul Lingor, MD

Role: CONTACT

paul.lingor@tum.de

+49 89 4140 8257

Andreas Wolff, MD

Role: CONTACT

andreas.wolff@tum.de

+49 89 4140 8237

Facility Contacts

Paul Lingor, MD

Role: primary

paul.lingor@tum.de

References

Wolff AW, Bidner H, Remane Y, Zimmer J, Aarsland D, Rascol O, Wyse RK, Hapfelmeier A, Lingor P. Protocol for a randomized, placebo-controlled, double-blind phase IIa study of the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with Parkinson's disease (ROCK-PD). Front Aging Neurosci. 2024 Feb 14;16:1308577. doi: 10.3389/fnagi.2024.1308577. eCollection 2024.

Reference Type: DERIVED

PMID: 38419648 (View on PubMed)

Other Identifiers

01EN2005

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ROCK-PD-0000-LIN-0075-I

Identifier Type: -

Identifier Source: org_study_id