Clinical trial NCT02462603: Safety and Biomarker Study of PTC-589 in Participants With Parkinson's Disease
Official title: A Phase 2A Safety and Biomarker Study of EPI-589 in Mitochondrial Subtype and Idiopathic Parkinson's Disease Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
PD
EPI-589
EPI589
Lead sponsor: Edison Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2015-06-04
Enrollment: 44
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label study with 30-day run-in phase and adaptive design component to include more participants if deemed appropriate by investigators.

Detailed description: This is a within-subject, controlled open-label study seeking to determine if PTC-589 can alter the biochemical signature of Parkinson's disease as assessed by peripheral blood biomarkers, central nervous system (CNS) biomarkers, and urine biomarker analysis. In addition, data on a number of disease-relevant clinical measures will be collected.

Eligibility criteria: Inclusion Criteria:

* Hoehn and Yahr stage ≤3.0
* Ambulatory with or without assistance
* Sexually active fertile participants and their partners must agree to use medically accepted methods of contraception (such as, hormonal methods, including oral, subcutaneous, and intrauterine; barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the last dose of study treatment.
* Willingness and ability to comply with study procedures
* If on medications for Parkinson's disease drugs, then medication regimen must be stable for 60 days prior to enrollment
* Abstention from use of other investigative or non-approved drugs for the duration of the trial

For Idiopathic Participants

* A diagnosis of idiopathic Parkinson's disease confirmed by the presence of bradykinesia plus one or both of the following symptoms: rigidity or resting tremor; and with an abnormal DaTscan consistent with a dopaminergic deficit
* Age 40 to 75 years
* Within 5 years of diagnosis of Parkinson's disease

For Genetic Subtype Participants

* A confirmed diagnosis of Parkinson's disease plus a genetic diagnosis consistent with Parkinson's disease, specifically PTEN-induced kinase 1 (PINK1), parkin, Leucine-rich repeat kinase 2 (LRRK2) or other mitochondrial genetic subtype
* Age 21 to 75 years

Exclusion Criteria:

* Allergy to PTC-589 or other components of the PTC-589 tablet formulation
* Use of antioxidant supplements, specifically vitamins E and C beyond the recommended daily allowance
* Other Parkinsonian disorders
* Montreal Cognitive Assessment (MoCA) score of \<24
* Revised Hamilton Rating Scale for Depression ≥11
* Parkinsonism due to drugs or toxins
* Diagnosis of any other clinically significant neurologic disease that will confound the assessment of effect of study drug on disease progression
* Malignancy within past 2 years
* Pregnant or plans to become pregnant or breast feeding
* History of stroke
* History of brain surgery
* Hepatic insufficiency with liver function tests (LFTs) \>3 times upper limit of normal
* Renal insufficiency as defined by creatinine \>1.5 times normal
* End stage cardiac failure
* Participation within past 3 months and for duration of study in a trial of a device, drug, or other therapy for Parkinson's disease

Primary outcomes:
measure: Number of Participants With Drug-Related Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (up to 4 months)
Secondary outcomes:
measure: Change From Baseline in Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Score at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in Non-motor Symptoms Scale (NMSS) Total Score at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in Parkinson's Disease Questionnaire - 39 (PDQ-39) Score at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in EuroQol-5 Dimension (EQ-5D) Score at Month 3
timeFrame: Baseline, Month 3
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: Month 3
measure: Beck Depression Inventory (BDI) Score
timeFrame: Month 3
measure: Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in Time to Complete Time Up and Go (TUG) Test in ON State at Month 3
timeFrame: Baseline, Month 3
measure: Maximum Observed Plasma Concentration (Cmax) of PTC589
timeFrame: 0 hour (predose) and 0.5, 1, 2, 4, 6, 8, and 12 hours postdose at Month 1 and 3
measure: Level of Disease-Related Biomarker (Glutathione) in Plasma
timeFrame: Month 3
measure: Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
timeFrame: Month 3
measure: Level of Disease-Related Biomarker (Glutathione) in Urine
timeFrame: Month 3
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedar's Sinai
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Tuebingen
country: Germany
facility: DZNE Site
city: London
country: United Kingdom
facility: University College of London,Dept. of Clinical Neuroscience
Study officials:
affiliation: Edison Pharmaceuticals
name: Matthew B Klein, MD FACS
role: STUDY_DIRECTOR
References: