A Clinical Study of IRL790 in Patients With Parkinson's Disease Experiencing Levodopa Induced Dyskinesia

• ClinicalTrials.gov Identifier: NCT03531060
• Recruitment Status: Completed
• First Posted: May 21, 2018
• Last Update Posted: May 21, 2018
• Sponsor: Integrative Research Laboratories AB
• Information provided by (Responsible Party): Integrative Research Laboratories AB

Study Description

Brief Summary:

This is a Phase 1b study investigating the safety and tolerability of IRl790 as adjunct therapy in patients with Parkinson disease. IRL790/placebo is taken for 28 days.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Drug: IRL790; Drug: Placebo	Phase 1; Phase 2

Detailed Description:

Consenting patients were screened for eligibility as per study-specific inclusion/exclusion criteria within 8-28 days before start of Investigational Medicinal Product (IMP) administration (Visit 1; Screening Visit). At Visit 2 (Day -7) a kinetigraph device (the Parkinson's KinetiGraph™, Global Kinetics Corporation, Melbourne, Victoria, Australia) was attached to the right or left wrist (the parkinsonian dominant side) and baseline patient movement data were recorded during a run-in period of seven consecutive days.

Following baseline assessments at Visit 3 (Day 1) patients were randomized to receive IRL790 or placebo (3:1). The treatment allocation was double-blinded, i.e. it was not disclosed to the patients, the site staff or the Sponsor. During the treatment period, Visits 4-8 were performed on Days 4, 7, 10, 14 and 28 (end of treatment) and a follow-up phone call was performed on Day 21. Dose adjustments of IRL790 could be made until Day 14, following pre-defined criteria. A follow-up visit (Visit 9) was performed 7-10 days after the last IMP dose.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled, Phase Ib Study Evaluating the Safety and Tolerability of IRL790 in Patients With Parkinson's Disease (PD) Experiencing Levodopa (L-Dopa) Induced Dyskinesia (LID).
• Actual Study Start Date: November 8, 2016
• Actual Primary Completion Date: April 12, 2017
• Actual Study Completion Date: April 12, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: IRL790; IRL790 Capsule 10 mg, oral administration	Drug: IRL790; IRL790 capsule 10 mg
Placebo Comparator: Placebo; Placebo capsule, identical appearance, oral administration	Drug: Placebo; Placebo capsule

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: 4 weeks ]
   Medical Dictionary for Regulatory Activities Preferred Term
2. Physical examination [ Time Frame: 4 weeks ]
   Number of participants with clinically significant abnormal physical examination findings
3. Electrocardiogram (ECG) recordings [ Time Frame: 4 weeks ]
   Number of participants with clinically significant abnormal electrocardiogram readings
4. Heart rate [ Time Frame: 4 weeks ]
   Beats per minute
5. Blood pressure [ Time Frame: 4 weeks ]
   mm Hg
6. Safety laboratory measurements [ Time Frame: 4 weeks ]
   Number of participants with clinically significant abnormal laboratory values

Secondary Outcome Measures :

1. Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 4 weeks ]
   The change from baseline to day 28 of treatment (Visit 4) in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). The UDysRS is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia.
2. Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: 4 weeks ]
   The UPDRS assess symptoms of Parkinson's disease. The scoring range from 0-199, where higher score means more severe disease.
3. Parkinson Kinetigraph (PKG) [ Time Frame: Change from run-in to week 4 of treatment ]
   Wrist worn kinetigraph capturing electronic readings of movement activity.
4. Clinical Global impression of change (CGI-C) [ Time Frame: 4 weeks ]
   Global impression of change
5. Pharmacokinetic assessment [ Time Frame: 4 weeks ]
   Plasma concentration at Cmax
6. Pharmacokinetic assessment [ Time Frame: 4 weeks ]
   Trough level plasma concentration

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female aged 50-85 years inclusive.
2. Female patients had to be of non-childbearing potential (defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal females defined as 12 months of amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulation hormone (FSH) 25-140 IE/L and estradiol <200 pmol/L was confirmatory]).
3. Male patients had to be willing to use condom and contraceptive methods with a failure rate of < 1% to prevent pregnancy7 and drug exposure of a partner and refrain from donating sperm from the date of dosing until three months after dosing of the IMP.
4. A diagnosis of idiopathic PD according to the United Kingdom Parkinson's Disease Society brain bank diagnostic criteria.
5. Showing a clear peak-dose dyskinetic response to regular L-Dopa medication. Patients with additional complex dyskinesia patterns including, but not limited to, diphasic dyskinesias or end of dose dyskinesias could be included if peak dose dyskinesias were also present.
6. On stable doses of anti-parkinson treatment for at least one month prior to inclusion and expected to remain stable on the same doses throughout the study.
7. Clinical laboratory tests within normal limits or clinically acceptable to the Investigator/Sponsor.
8. Able to understand study specific procedures and willing and able to give written informed consent for participation in the study.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, could either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
2. History of or present clinically significant psychiatric diagnosis, at discretion of the Investigator.
3. History of seizures, including febrile seizure in childhood.
4. History or presence of hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
5. Any clinically significant illness, medical/surgical procedure or trauma within four weeks of the first administration of IMP.
6. Any planned major surgery within the duration of the study.
7. Previous surgery for PD. . A Hoehn and Yahr score of 5 when "off".

9. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.

10. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL790. 11. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study that included drug treatment with less than three months between administration of last dose and first dose of IMP in this study. 12. History of alcohol abuse and/or use of drugs of abuse. 13. Investigator considered the patient unlikely to comply with study procedures, restrictions and requirements.

Contacts and Locations

Sponsors and Collaborators

Integrative Research Laboratories AB

Investigators

• Principal Investigator: Per Svenningsson, MD, PhD; Karolinska Institutet, Stockholm

More Information

• Responsible Party: Integrative Research Laboratories AB
• ClinicalTrials.gov Identifier: NCT03531060
• Other Study ID Numbers: IRL790C002
• First Posted: May 21, 2018
• Last Update Posted: May 21, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Parkinson Disease; Dyskinesias; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Neurologic Manifestations