A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease
Study Details
Study Description
Brief Summary
This study investigates the safety and tolerability of drug IkT-148009 in untreated Parkinson's disease volunteers (55 to 75 years old). It also looks at the pharmacokinetics of IkT-148009 in the body and evaluates the effect of ikT-148009 on motor and non-motor features of the disease. This 12 week study is designed to be 3:1 randomized across 3 doses of IkT-148009 or placebo. Each participant will self-administer one of 3 doses or placebo of IkT-148009 once daily (QD) with food for 12 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a 12-Week, randomized, double-blind, multi-center, placebo-controlled dose-ranging clinical trial of three IkT 148009 doses in patients with untreated PD designed to assess safety, tolerability, and pharmacokinetics of IkT-148009, an oral, once daily c-Abl tyrosine kinase inhibitor. Secondary and exploratory assessments will evaluate the effect of IkT-148009 on motor and non-motor features of the disease. 120 participants are anticipated to be enrolled at up to 40 sites across the US.
Participants will undergo screening to evaluate their eligibility to participate in the study to include evaluation of Parkinson's diagnosis, vital signs, blood chemistry, hematology and urinalysis and complete listing of concomitant medications. An Enrollment Authorization Committee (EAC) will be responsible for reviewing screening data and confirming the eligibility and suitability of participants. Those selected will be enrolled and randomized to one of three active IkT-148009 arms (50/100/200 mg) or a placebo arm (3:1). All clinical staff, study investigators, and participants will be blinded to study assignments throughout the trial.
A Data Safety Monitoring Committee (DSMB) will evaluate all available safety, tolerability, and PK and Parkinson's disease-related data for each cohort on a monthly to quarterly basis. Adverse event reporting will be evaluated in real-time.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 50mg IkT-148009 This arm will consist of thirty (30) patients on 50mg of active treatment. |
Drug: IkT-148009
Oral administration gelatin capsule
|
| Experimental: 100mg IkT-148009 This arm will consist of thirty (30) patients on 100mg of active treatment. |
Drug: IkT-148009
Oral administration gelatin capsule
|
| Experimental: 200mg IkT-148009 This arm will consist of thirty (30) patients on 200mg of active treatment. |
Drug: IkT-148009
Oral administration gelatin capsule
|
| Placebo Comparator: Placebo This arm will consist of thirty (30) patients on placebo. |
Drug: Placebo
Oral administration gelatin capsule
|
Outcome Measures
Primary Outcome Measures
- Incidence and temporal profile of treatment-emergent adverse events (TEAEs) evaluated by type/nature, severity/intensity, seriousness, and relationship to study intervention [Day 1 through week 16]
- Proportion of those randomized in each dosing cohort who discontinued the assigned regimen [Day 1 through week 12]
Secondary Outcome Measures
- Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II + III [Change from Baseline to Week 12]
Higher scores mean worse outcome from 0 to 52
- Patient Global Impression-Severity (PGI-S) [Change from Baseline to Week 12]
Scale varies from None to Very Severe
- Clinician Global Impression of Severity (CGI-S) [Change from Baseline to Week 12]
Higher scores mean worse outcome between 1 and 7.
- Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I [Change from Baseline to Week 12]
Higher scores mean worse outcome from 0 to 52.
- Non-Motor Symptom Scale (NMSS) [Change from Baseline to Week 12]
Higher scores mean worse outcome from 0 to 360.
- Complete Spontaneous Bowel Movement (CSBM) [Change from Baseline to Week 12]
A value < 3 implies constipation
- Epworth Sleepiness Scale (ESS) [Change from Baseline to Week 12]
Higher score means worse outcome from 0 to 24.
- Schwab and England Activities of Daily Living (SE-ADL) Scale [Change from Baseline to Week 12]
Higher score means worse outcome from 0% to 100%
- Parkinson's Disease Questionnaire (PDQ-39) [Change from Baseline to Week 12]
Higher scores mean worse outcome from 0 to 100.
- Patient Assessment of Upper Gastrointestinal Disorders Severity Index (PAGI-SYM) [Change from Baseline to Week 12]
Higher score means worse outcome from 0 to 100.
- Patient Assessment of Constipation Quality of Life (PAC-QOL) [Change from Baseline to Week 12]
Higher score means worse outcome from 0 to 150.
- Patient Assessment of Gastrointestinal Disorders Severity Quality of Life (PAGI- QOL) [Change from Baseline to Week 12]
Higher score means worse outcome from 0 to 150.
Other Outcome Measures
- WGTT Exploratory [Change from Baseline to Week 12]
Whole Gut Transit Time (WGTT) by SmartPill. This measures the time it takes for a digital capsule to pass through the stomach, small intesting, colon and the sum of these values to obtain the WGTT. Higher score means worse outcome.
- Phosphorylated alpha-synuclein in cerebrospinal fluid (CSF) [Change from Baseline to Week 12]
Detection of the presence or absence of phosphorylated alpha-synuclein in CSF
- Phosphorylated alpha-synuclein in skin [Change from Baseline to Week 12]
Detection of the presence or absence of phosphorylated alpha-synuclein in peripheral nerve biopsy in skin
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants who are diagnosed with PD consistent with UK Brain Bank criteria and MDS Research Criteria; must include bradykinesia with sequence effect and motor asymmetry.
-
Receiving no anti-parkinsonian therapy
-
Modified Hoehn/Yahr Stage < 3.0
-
Montreal Cognitive Assessment ≥ 26
-
Patient expected to be able to participate in trial without need for additional anti-parkinsonian therapy
-
Capable of giving signed ICF as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
-
Approved as an appropriate and suitable candidate by the EAC.
Sex and Contraceptive/Barrier Requirements:
Male participants:
- Male participants must agree to practice an acceptable method of highly effective birth control from the screening visit, while on study and for 30 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence, vasectomy, or a condom with spermicide (men) in combination with their partner's highly effective method.
Female participants:
- Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and at least 30 days after the last dose of study drug has been taken.
Exclusion Criteria:
-
Diagnosis/suspicion of secondary or atypical parkinsonism
-
Previous procedure or surgery for PD, or anticipation of these during the study
-
High likelihood of needing anti-parkinsonian treatment over the study period, in the opinion of the investigator
-
Clinically significant orthostatic hypotension
-
Clinically significant hallucinations requiring antipsychotic use in the 12 months prior to Screening
-
Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in the judgement of the treating investigator or the EAC
-
Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors, or A2A antagonists for more than 28 days, or treatment with any of these medications within 28 days prior to screening
-
Past treatment with irreversible monoamine oxidase-B inhibitors (e.g., selegiline) for more than 28 days; must be discontinued for at least 90 days before screening
-
Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or CYP3A4/5 inhibitors (except for topical administration)
-
Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine.
-
Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening
-
Previous randomization into this or another IkT-148009 study
-
Active suicidal ideation within one year prior to screening visit, as determined by the Columbia Suicide Rating Scale (answer of "yes" on question 4 or 5)
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Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria
-
Medical or recreational use of marijuana in the 3 months prior to the screening visit
-
Any social or behavioral reason that would preclude completion of the study, in the judgement of the investigator
-
Any skin condition that would interfere with obtaining adequate samples
-
Abnormal amylase and/or lipase at screening (may be repeated during screening period)
-
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)
-
Significant renal impairment as determined by creatinine clearance (CrCL) less than or equal to 60 ml/min
-
Currently lactating, pregnant or planning on becoming pregnant during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neurologist | Tampa | Florida | United States | 33592 |
Sponsors and Collaborators
- Inhibikase Therapeutics, Inc.
Investigators
- Principal Investigator: Sydney Kruger, Inhibikase Therapeutics, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IkT-148009-201