A Multiple Ascending Dose Study With LY03003 in Patients With Early-stage Parkinson's Disease

NCT04045678 | Completed Phase 1

• 1 other identifier: LY03003/CT-CHN-103
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This study is to evaluate the safety and tolerability and to characterize the pharmacokinetics of multiple ascending dose (MAD) of LY03003 following intramuscular injections.

Conditions

Parkinson Disease

Keywords

parkinson disease; LY03003

Outcome Measures

Primary Outcomes (1)

• Frequency of adverse events

  Adverse events to evaluate the safety and tolerability of LY03003

  From screening up to day 50

Secondary Outcomes (13)

• Time of maximum concentration (Tmax) of total LY03003

  From the first injection of stable doses up to day 50

• Maximum concentration in plasma (Cmax) of total LY03003

  From the first injection of stable doses up to day 50

• Area under the concentration-time curve (AUC) from zero up to the last measured concentration [AUC (0-t)] of LY03003

  From the first injection of stable doses up to day 50

• Area under the concentration-time curve (AUC) from time zero up to the infinite time [AUC (0-∞)] of LY03003

  From the first injection of stable doses up to day 50

• Apparent volume of distribution (Vd) of LY03003

  From the first injection of stable doses up to day 50

Study Arms (2)

LY03003

EXPERIMENTAL

Drug: LY03003 ( Rotigotine, extended-release microspheres)

Placebo

PLACEBO COMPARATOR

Drug: Placebo, extended-release microspheres

Interventions

LY03003 ( Rotigotine, extended-release microspheres) DRUG

Patients to be enrolled to 70 mg dose group will receive 14 mg in the first week, 28 mg in the second week, 42 mg in the third week,56 mg in the fourth week and then 70 mg in the next 5 weeks. Patients to be enrolled to 84 mg dose group will receive 14 mg in the first week, 28 mg in the second week, 42 mg in the third week,56 mg in the fourth week, 70mg in the fifth week and then 84 mg in the next 5 weeks.

LY03003

Placebo, extended-release microspheres DRUG

Patients to be enrolled to 70 mg dose group will receive 14 mg in the first week, 28 mg in the second week, 42 mg in the third week,56 mg in the fourth week and then 70 mg in the next 5 weeks. Patients to be enrolled to 84 mg dose group will receive 14 mg in the first week, 28 mg in the second week, 42 mg in the third week,56 mg in the fourth week, 70mg in the fifth week and then 84 mg in the next 5 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient had Parkinson's Disease that meet the clinical diagnostic criteria of the brain bank of the Parkinson's Disease Association of the United Kingdom.
• Patient was Hoehn \& Yahr stage ≤3 (excluding stage 0) ;
• Patient was male or female aged 18 to 75 years;
• Patient had a Mini Mental State Examination (MMSE) score of ≥25;
• Patient had a Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) of ≥10 but ≤30 at Screening.
• Patient who signed the informed consent form volunteered to participate in this clinical trial and could cooperate with the prescribed inspections.

You may not qualify if:

• Patient had atypical Parkinson's syndrome(s) due to drugs (e.g., metoclopramide, flunarizine), metabolic neurogenetic disorders (e.g., Wilson's disease), encephalitis, cerebrovascular disease, or degenerative disease (e.g., progressive supranuclear palsy);
• Patient had a history of pallidotomy, thalamotomy, deep brain stimulation, or fetal tissue transplant;
• Patient had dementia, schizophrenia or hallucinations, or clinically significant depression;
• Patient had a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or presence of suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening;
• Patient had a history of orthostatic hypotension with a decrease of ≥20 mmHg in systolic blood pressure (SBP) or ≥10 mmHg in diastolic blood pressure when changing from the supine to the standing position and keeping in the standing position for 3 minutes;
• Patient had received therapy with a dopamine (DA) agonist either concurrently or had done so within 28 days prior to the Screening;
• Patient had received therapy with 1 of the following drugs either concurrently or within 28 days prior to Screening: monoamine oxidase B (MAO-B) inhibitors (e.g., pargyline, selegiline), DA releasing agents (e.g., amphetamine), reserpine, DA-antagonists (e.g., metoclopramide), neuroleptics, or other medications that may interact with DA function;
• Patient was currently (at the time of Screening) receiving central nervous system active therapy (e.g., sedatives, hypnotics, antidepressants, anxiolytics), unless the dose had been stable for at least 28 days prior to Screening Visit and was likely to remain stable for the duration of the study;
• Patient had a current diagnosis of epilepsy, had a history of seizures as an adult within 1 year prior to Screening, had a history of stroke or transient ischemic attack within 3 months prior to Screening;
• Patient had a history of known intolerance/hypersensitivity to non-dopaminergic antiemetics, such as domperidone, ondansetron, tropisetron;
• Patient had clinically significant liver dysfunction (which defined as total bilirubin above the upper limit of normal range, or alanine transferase (ALT) and / or aspartate transferase (AST) 2 times higher than the upper limit of normal range);
• Patient had clinically significant renal insufficiency (serum creatinine \>2.0 mg/dL \[ \>178 μmol/L\]);
• Patient had clinically significant cardiac insufficiency and/or had myocardial infarction in the past 12 months;
• Patient had a history of allergic to any medication;
• Heavy smoker, alcoholic, drug addict;

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead
• Beijing Bozhiyin T&S Co., Ltd.: collaborator

Study Sites (3)

Chinese PLA General Hospital

Beijing, China

Location

Xuanwu Hospital Capital Medical University

Beijing, China

Location

Shengjing Hospital of China Medical University

Shenyang, China

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 5, 2019
• Study Start: October 10, 2017
• Primary Completion: April 16, 2019
• Study Completion: June 21, 2019
• Last Updated: September 22, 2020

Record last verified: 2020-09

Locations

CN (3)