Pharmacokinetics and Safety Study of LY03003 in Patients With Early-stage Parkinson's Disease (03003MAD)

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

The purpose of this study is to characterize the pharmacokinetics (PK) of LY03003 following multiple escalating intramuscular injections, as compared to Neupro patch and to evaluate the safety and tolerability and preliminary efficacy of multiple ascending dose (MAD) of LY03003 following intramuscular injections.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: LY03003; Drug: Neupro

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Network LLC
  • Florida
    • Orlando, Florida, United States, 32806
      • Compass Research LLC
  • Georgia
    • Douglasville, Georgia, United States, 30134
      • West Georgia Sleep Disorders Center and Neurology Associates
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Quest Research Institute
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • PRA - CRI Lifetree

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has Idiopathic Parkinson's Disease defined by the cardinal sign, Bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism
2. Subject is Hoehn & Yahr stage ≤3
3. Subject is male or female aged ≥18 years at Screening
4. Subject has a Mini Mental State Examination (MMSE) score of ≥25
5. Subject has a Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) of ≥10 but ≤30 at Screening

Exclusion Criteria:

1. Subject has 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. Subject has a history of Pallidotomy, Thalamotomy, deep brain stimulation, or fetal tissue transplant
3. Subject has dementia, active psychosis or hallucinations, or clinically significant depression
4. Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has 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 (CSSRS) at Screening
5. Subject has a history of symptomatic orthostatic hypotension with a decrease of ≥20 mmHg in systolic blood pressure (SBP) or ≥10 mmHg in diastolic blood pressure when changing from supine to standing position after having been at supine position for at least 5 minutes within 28 days prior to the Screening Visit, or SBP less than 105 mmHg at study entry, or reports clinical signs of clinically significant orthostatic hypotension within 28 days prior to the Screening Visit.
6. Subject is receiving therapy with a dopamine agonist (DA) either concurrently or has done so within 28 days prior to the Screening
7. Subject is receiving therapy with 1 of the following drugs either concurrently or within 28 days prior to screening: MAO-B inhibitors, DA releasing agents, DA modulating agent, DA antagonists, neuroleptics, or other medications that may interact with DA function.
8. Subject is currently receiving central nervous system active therapy (e.g., sedatives, hypnotics, antidepressants, anxiolytics), unless the dose has been stable for at least 28 days prior to Screening Visit and is likely to remain stable for the duration of the study. Patients should not take those medications within 8 hours prior to clinical visits
9. Subject has a current diagnosis of epilepsy, has a history of seizures as an adult, has a history of stroke, or has had a transient ischemic attack within 1 year prior to Screening
10. Subject has a history of known intolerance/hypersensitivity to non-dopaminergic antiemetics, such as domperidone, ondansetron, tropisetron, and glycopyrrolate
11. Subject has any other clinically relevant hepatic, renal and cardiac dysfunction, or other medical condition or laboratory abnormality including abnormal plasma magnesium level, which would in the judgment of the investigator, interfere with the subject's ability to participate in the study
12. Subject has a history of significant skin hypersensitivity to adhesive or other transdermal preparations or recent unresolved contact Dermatitis (this item is specific for patients to be enrolled to part 2 of this study)
13. Subjects with C-reactive protein levels of 2x of upper limit of normal range
14. Female subjects who are pregnant or are breastfeeding or are of childbearing potential without adequate contraception.
15. Patients with a positive finding in drug screening test or alcohol test

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY03003; 4 Stable doses of LY03003 14, 28, 42 and 56 mg	Drug: LY03003
Active Comparator: Neupro; Neupro patch 2 mg/24 hours in the first week, and then be titrated to 4, 6 and 8 mg/24 hours at weekly intervals	Drug: Neupro
Active Comparator: Neupro PK; Neupro patch 2 mg/24hr in the first week then titrated to 4 and 6mg/24hr	Drug: Neupro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax for the Pharmacokinetics (PK) of LY03003	5 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	5 Weeks
Preliminary efficacy evaluation will be carried out based on Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III)	5 Weeks

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Investigators: Study Director: Simon Li, Luye Pharma Group Ltd.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Estimate): October 21, 2015
• Last Update Submitted That Met QC Criteria: October 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Parkinsons
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: LY03003