Phase II clinical study of TR-012001 in Japanese patients with Parkinson's disease

JRCT ID: jRCT2061230065

Registered date:12/10/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Parkinson's disease
• Date of first enrollment: 06/11/2023
• Target sample size: 12
• Study type: Interventional

Intervention(s)

Of the 12 subjects enrolled in the study, the study drug will be randomly assigned to 9 subjects of the TR-012001 group and 3 subjects of the placebo group.
Each subject must complete taking levodopa-containing preparations and other anti-parkinsonism medications by 9:00 p.m. on Day 2 and not take them after 9:00 p.m. until 3 hours after the next day's dose of study medication.
The investigational drug will be administered by the investigator as a single dose under fasting conditions after waking up on Day 3 of the study drug administration period. After 3 hours of administration of the study drug, the patient will take levodopa-containing drugs and anti-parkinsonism drugs according to the prescribed, daily dosage and administration.

Outcome(s)

Primary Outcome

(1)Safety evaluation of TR-012001
a) Adverse event (name of adverse event, date and time of onset, severity, seriousness, outcome, date and time of outcome, relationship to study drug)
b) Physical findings
c) Vital signs (body temperature, blood pressure, pulse rate)
d) Columbia Suicide Severity Rating Scale (C-SSRS)
e) Laboratory test values (hematological test, blood biochemical test, urinalysis) , etc.

(2)Plasma concentration and pharmacokinetic parameters of the API after administration of TR-012001
[Evaluation parameters] Maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), elimination half-life (t1/2), Area under the plasma concentration-time curve (AUC), mean residence time (MRT), apparent whole body clearance (CL/f), volume of distribution (Vd/f )

Key inclusion & exclusion criteria

• Age minimum: >= 30age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Japanese males and females aged 30 years or older at the time of informed consent.
(2) Patients diagnosed with idiopathic Parkinson's disease according to the UKPDS Brain Bank Parkinson's disease diagnostic criteria.
(3) Patients with Parkinson's disease stage 2-4 on the revised Hoehn & Yahr grading system in the on state.
(4) Patients who are taking levodopa-containing formulations* three times or more per day, with a daily dosage of 300 mg or more of levodopa.
*Levodopa-containing preparations: Levodopa/dopa decarboxylase inhibitor (DCI) combination preparations, DCI can be either carbidopa or benserazide.
(5) Patients who can maintain a fixed dosage and administration of levodopa-containing preparations and other antiparkinsonian drugs (only for patients taking medication) after obtaining informed consent until the end of the study.
(6) Patients who are found to be off in their daily life by patient evaluation.
(7) Females of childbearing potential* or males with female partners of childbearing potential* who agree to practice adequate contraception on a daily basis from the time consent is obtained until the end of the study.
* Female (partners) of childbearing potential: Women who have not confirmed menopause (no menstruation for 52 weeks or more counting from the start of the last menstrual period).
(8) Patients who are fully informed about the purpose and contents of this study before the start of screening, who understand the contents of the informed consent form, and who can sign their own will.

Exclude criteria

(1) Patients with non-idiopathic Parkinson's disease [atypical Parkinson's disease, secondary (acquired or symptomatic) Parkinson's disease, Parkinson's plus syndrome, etc.].
(2) Patients with hypersensitivity or allergy to the API or other ingredients used in the investigational drug, or patients with a history of severe allergy to other drugs (anaphylaxis, etc.).
(3) Patients with angle-closure glaucoma.
(4) Patients with disease or findings that are judged to affect this study from the viewpoint of safety and/or evaluation.
(5) Patients who received levodopa continuous enteral therapy (LCIG therapy: Levodopa-carbidopa continuous infusion gel treatment) or patients who plan to receive it during the study period.
(6) Patients who have used Apokyne subcutaneous injection 30 mg within 1 month prior to obtaining informed consent or patients who plan to use Apokyne during the study period.
(7) Patients who have undergone brain surgery for Parkinson's disease (pallidotomy, deep brain stimulation, etc.) or patients who plan to undergo such surgery during the study period.
(8) Patients who received or plan to receive transcranial magnetic stimulation therapy within 6 months prior to consent.
(9) Patients with a history or comorbidities of drug abuse or alcoholism.
(10) Patients with a history or complication of mental illness (schizophrenia, psychotic depression, etc.). However, psychiatric symptoms associated with Parkinson's disease are excluded.
(11) Patients with overt dementia or Mini-Mental State Examination (MMSE) score less than 24 points.
(12) Patients with a history of suicidal ideation or attempted suicide within the past year or a history of present illness.
(13) Patients with a history of malignant syndrome caused by antiparkinsonian drugs.
(14) Patients with clinically problematic brain, cardiovascular, hematological, autoimmune, endocrine, cardiovascular, renal, gastrointestinal, or respiratory diseases (including infectious diseases) that are judged by the investigator to have the potential to affect the conduct of this study from the perspective of safety and other factors.
(15) Patients with any of the following laboratory test results from screening tests:
- A creatinine level greater than or equal to 2x the laboratory upper limit
- Total bilirubin level greater than or equal to 3 times the laboratory upper limit
- ALT or AST greater than or equal to 3 times the laboratory upper limit
- ALP greater than or equal to 3 times the laboratory upper limit
(16) Patients who have clinically significant abnormalities in other tests (including clinical tests) in the screening test and are judged by the investigator to be inappropriate for participation in this study.
(17) Patients with acquired immunodeficiency syndrome (AIDS) (including patients who are either HIV antigen or antibody positive) or hepatitis (including patients who are HBs antigen positive or HCV antibody positive).
(18) Patients who required treatment for malignant tumors within 5 years before consent was obtained (excluding treated cervical intraepithelial neoplasia, cured nonmetastatic squamous or basal cell tumors of the skin).
(19) Patients who are scheduled for surgery requiring hospitalization during the study period or who are in a condition requiring surgery.
(20) Patients who are pregnant, breastfeeding, may be pregnant, or wish to become pregnant during the study period.
(21) Patients who have received all other unapproved drugs (including investigational drugs, drugs administered through clinical research, unapproved combination drugs, and new formulations) within 3 months prior to obtaining consent or within 5 times the half-life, whichever is longer.
(22) Patients who have received TR-012001 in the past.
(23) Patients who are deemed inappropriate for participation in this study by the investigator for any reason, including patients who have difficulty communicating or cooperating.

Related Information

• Primary Sponsor: Kanazashi Shuichi