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

September 21, 2020 updated by: Luye Pharma Group Ltd.

A Randomized, Double-blinded, Multiple Ascending Dose Study in Patients With Early-stage Parkinson's Disease to Evaluate the Pharmacokinetics and Safety of LY03003 Following Intramuscular Injections

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

Study Overview

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Beijing, China
        • Chinese PLA General hospital
      • Beijing, China
        • Xuanwu Hospital Capital Medical University
      • Shenyang, China
        • Shengjing Hospital of China Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.
  2. Patient was Hoehn & Yahr stage ≤3 (excluding stage 0) ;
  3. Patient was male or female aged 18 to 75 years;
  4. Patient had a Mini Mental State Examination (MMSE) score of ≥25;
  5. Patient had a Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) of ≥10 but ≤30 at Screening.
  6. Patient who signed the informed consent form volunteered to participate in this clinical trial and could cooperate with the prescribed inspections.

Exclusion Criteria:

  1. 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);
  2. Patient had a history of pallidotomy, thalamotomy, deep brain stimulation, or fetal tissue transplant;
  3. Patient had dementia, schizophrenia or hallucinations, or clinically significant depression;
  4. 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;
  5. 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;
  6. Patient had received therapy with a dopamine (DA) agonist either concurrently or had done so within 28 days prior to the Screening;
  7. 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;
  8. 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;
  9. 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;
  10. Patient had a history of known intolerance/hypersensitivity to non-dopaminergic antiemetics, such as domperidone, ondansetron, tropisetron;
  11. 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);
  12. Patient had clinically significant renal insufficiency (serum creatinine >2.0 mg/dL [ >178 μmol/L]);
  13. Patient had clinically significant cardiac insufficiency and/or had myocardial infarction in the past 12 months;
  14. Patient had a history of allergic to any medication;
  15. Heavy smoker, alcoholic, drug addict;
  16. Female patients who were pregnant or were breastfeeding or were of childbearing potential without adequate contraception; male patients who cannot take adequate contraception during the study;
  17. Patient who was inappropriate to participant in the study in the judgment of the Investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo

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.

Experimental: LY03003

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events
Time Frame: From screening up to day 50
Adverse events to evaluate the safety and tolerability of LY03003
From screening up to day 50

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time of maximum concentration (Tmax) of total LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Maximum concentration in plasma (Cmax) of total LY03003
Time Frame: From the first injection of stable doses up to day 50
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
Time Frame: From the first injection of stable doses up to day 50
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
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Apparent volume of distribution (Vd) of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Terminal half-life (t1/2) of total LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Total body clearance of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Maximum steady-state drug concentration of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Minimum steady-state drug concentration of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Average steady-state concentration of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Area under the concentration-time curve (AUC) at steady-state concentration of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Fluctuation degree in steady-state concentration of LY03003
Time Frame: From the first injection of stable doses up to day 50
From the first injection of stable doses up to day 50
Change from baseline to the end of the treatment period in the Unified Parkinson's Disease Rating Scale (UPDRS) part (Ⅱ+Ⅲ) Total Score
Time Frame: Screening, baseline, days 29 and day 50

The Unified Parkinson´s Disease Rating Scale Part Ⅱ measures "Activities in Daily Living". The total score ranges from 0 (Best score possible) to 52 (Worst score possible).

The Unified Parkinson´s Disease Rating Scale Part Ⅲ is an accepted and validated scale for the assessment of motor function in Parkinson´s disease. Each of the 27 sub-items in the UPDRS III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. The total scores therefore ranges from 0 to 108.

Screening, baseline, days 29 and day 50

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2017

Primary Completion (Actual)

April 16, 2019

Study Completion (Actual)

June 21, 2019

Study Registration Dates

First Submitted

July 30, 2019

First Submitted That Met QC Criteria

August 2, 2019

First Posted (Actual)

August 5, 2019

Study Record Updates

Last Update Posted (Actual)

September 22, 2020

Last Update Submitted That Met QC Criteria

September 21, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Parkinson Disease

Clinical Trials on LY03003 ( Rotigotine, extended-release microspheres)

3
Subscribe