A Clinical Study in Parkinson’s Disease Patients With Moderate to Severe Abnormal Movements to See If JM-010 is Effective and Safe/Tolerable.

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2017-003415-19-ES
• Date of registration: 20/08/2018
• Prospective Registration: Yes
• Primary sponsor: Contera Pharma
• Public title: A Clinical Study in Parkinson’s Disease Patients With Moderate to Severe Abnormal Movements to See If JM-010 is Effective and Safe/Tolerable.
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study in Parkinson’s Disease Patients With Moderate to Severe Dyskinesia to Assess the Efficacy and Safety/Tolerability of Two Dose Combinations Of JM-010
• Date of first enrolment: 31/10/2018
• Target sample size: 81
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003415-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Spain

Contacts

• Name: Clinical Trials Information
• Affiliation: Contera Pharma

• Name: Clinical Trials Information
• Affiliation: Contera Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
1. Is able to read, understand, and provide written, dated informed consent prior to Screening Visit. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events (AEs) and other clinically important information.
2. Is male or female, between 18 and 80 years of age at Screening Visit.
3. Is diagnosed with idiopathic PD that meets UK Parkinson’s Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria and requires treatment with and shows responsiveness to levodopa.
4. Has experienced dyskinesia over a period of at least 3 months prior to Screening Visit
5. Has stable peak-effect dyskinesia (as reported by the subjects); the dyskinesia should be moderately to completely disabling (MDS-UPDRS, Part IV, item 4.2, rating = 3).
6. Has more than one hour of “ON” time with troublesome dyskinesia during daily waking hours on a 24-hour PD subject diary on each of 2 consecutive days just prior to Visit 2, Week 0 (Baseline Visit).
7. Is on a stable levodopa dosing regimen requiring at least 3 dose administrations but no more than 6 dose administrations per day with at least 2 to 3 hour intervals between 2 successive doses of levodopa for at least 30 days prior to Screening Visit, and is expected to continue this levodopa regimen with no changes for the duration of study participation.
8. Must be on a stable dosing regimen if taking other anti-parkinsonian medication(s) and is expected to continue this regimen with no changes for the duration of study participation.
9. Is willing and able to stop using amantadine and/or monoamine oxidase inhibitors (MAOi), where applicable, from at least 4 weeks prior to Visit 2, Week 0 (Baseline Visit) and for the duration of study participation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41

Exclusion criteria:
A potential subject will not be eligible for participation in this study if any of the following criteria are met:
PD-Specific Criteria:
1. Has undergone surgery for the treatment of PD (e.g., pallidotomy, deep brain stimulation, fetal tissue transplantation) or has undergone any other major brain surgery.
Criteria related to psychiatric and other neurological disorders:
2. Has current diagnosis of Substance Use (including alcohol) Disorder (Abuse or Dependence, as defined by DSM 5th Edition), with the exception of caffeine and nicotine dependence, at Screening Visit or within 12 months prior to Screening Visit.
3. Has psychiatric diagnosis of acute psychotic disorder or other psychiatric diagnoses such as bipolar disorder or major depressive disorder, or generalized anxiety disorder that are clinically predominant to their PD or have been predominant to their PD at any time within 6 months prior to Screening Visit.
4. Has other psychiatric (not including hallucinations due to side effects of dopamine therapy), neurological or behavioral disorders that in the opinion of the investigator may interfere with the conduct or interpretation of the study, including dementia, or subject who is considered violent.
5. Has a significant risk for suicidal behavior in the opinion of the investigator during the course of their participation in the study or
• At Screening Visit: the subject scores “yes” on items 4 or 5 in the Suicidal Ideation section of the C-SSRS with reference to a 6-month period prior to Screening Visit; or
• At Screening Visit: the subject has had one or more suicidal attempts with reference to a 2-year period prior to Screening Visit; or
• At Baseline Visit: the subject scores “yes” on items 4 or 5 in the Suicidal Ideation section of the C SSRS with reference to Screening Visit; or
6. Has current seizure disorders (other than febrile seizures in childhood) requiring treatment with anti convulsants.
7. Has known serious ongoing symptomatic cerebral disease or cerebrovascular disease or any acute brain trauma requiring treatment with anti-convulsant therapy within 5 years prior to Screening Visit.
8. Has history of exclusively diphasic, OFF state, myoclonic, dystonic, or akathetic dyskinesia without peak dose dyskinesia.
Criteria related to other medical conditions:
9. Has current evidence of clinically significant hematological, autoimmune, endocrine, cardiovascular, peripheral vascular, renal or gastrointestinal disorder or other known condition (eg. porphyria, unstable diabetes mellitus) that would possibly interfere with the subject’s participation in the study and/or assessments.
10. Has any malignant disease or a history of neoplasms treated within the 5 years prior to the Screening Visit, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin.
11. Has orthostatic or symptomatic hypotension: a decrease of > 20 mm Hg in SBP and/or > 10 mm Hg in DBP after at least 3 minutes standing compared to the previous supine BP in 2 separate measurements and/or history or current episode of repeated hypotensive or vasovagal syncope.
12. Has known history or current episode of:
• History of stroke or transient ischemic attack within 2 years prior to screening
• History of myocardial infarction, or New York Heart Association Functional Classification of Heart Failure Class 3 or 4 within 2 years prior to screening.
• Any clinically significant ECG abnormalities, including any findings of abnormal ventricular con

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson’s Disease Patients With Moderate to Severe Dyskinesia

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: JM-010
Product Code: JM-010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Buspirone hydrochloride
CAS Number: 33386-08-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
INN or Proposed INN: Zolmitriptan
CAS Number: 139264-17-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.8-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: JM-010
Product Code: JM-010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Buspirone hydrochloride
CAS Number: 33386-08-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
INN or Proposed INN: Zolmitriptan
CAS Number: 139264-17-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.8-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the UDysRS total score change from Baseline to Week 12.

Secondary Objective: To compare the efficacy of JM-010 (administered as 2 different dose combinations of JM-010) to that of placebo therapy in relation to:
• Change in parkinsonian disability/disease progression as measured by the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I to IV
• Improvement in clinician-reported PD symptoms as measured by the Clinician Global Impression of Change (CGI-C)
• Change in ON time with troublesome dyskinesia, ON time with non-troublesome dyskinesia, ON time without dyskinesia, and OFF time as measured by Hauser diaries
To determine the safety and tolerability of JM-010 (administered as 2 different dose combinations of JM-010) to that of placebo therapy. Safety and tolerability will be assessed in relation to:
• Incidence of treatment-emergent adverse events (TEAEs)
• Clinical laboratory evaluations
• 12-lead electrocardiogram (ECG) assessments
• Vital signs
• Columbia Suicide Severity Rating Scale (C-SSRS)

Timepoint(s) of evaluation of this end point: Week 0, 2, 4, 8, 12

Main Objective: To compare the efficacy of JM-010 (administered as 2 different dose combinations of JM-010) to that of placebo therapy in reducing dyskinesia severity in PD by evaluating the mean change from Baseline to Week 12 on the Unified Dyskinesia Rating Scale (UDysRS).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 0, 2, 4, 8, 12

Secondary end point(s): The secondary efficacy endpoints include the following:
1. UDysRS total score changes from Baseline
2. MDS-UPDRS Part III score changes from Baseline
3. CGI-C score
4. ON time without troublesome dyskinesia (ON time without dyskinesia plus ON time with non-troublesome dyskinesia) changes from Baseline
5. OFF time changes from Baseline
6. ON time with troublesome dyskinesia changes from Baseline
7. Total time with dyskinesia (non-troublesome and troublesome) changes from Baseline
8. UDysRS Total Objective Score (Parts III and IV) changes from Baseline
9. MDS-UPDRS, individual (Parts I, II, III, and IV) and combined scores (Parts I, II, and III) changes from Baseline

Secondary ID(s)

JM-010CS03

Source(s) of Monetary Support

Contera Pharma

Ethics review

Status: Approved
Approval date:
Contact: