Parkinson Disease
Conditions
Keywords
Untreated Parkinsons disease
Brief summary
This study investigates the safety and tolerability of drug IkT-148009 in untreated Parkinson's disease volunteers (30 to 80 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. For more information, visit our website: www.the201trial.com
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 34 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 (1:1:1:1). 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.
Interventions
DRUGIkT-148009 (risvodetinib)
Oral administration gelatin capsule
DRUGPlacebo
Oral administration gelatin capsule
Sponsors
ABLi Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Receiving no anti-parkinsonian therapy 3. Modified Hoehn/Yahr Stage \< 3.0 4. Montreal Cognitive Assessment ≥ 24 5. Patient expected to be able to participate in trial without need for additional anti-parkinsonian therapy Sex and Contraceptive/Barrier Requirements: 1. 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. 2. 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. Informed Consent: 1\. 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. Other Inclusions: 1\. Approved as an appropriate and suitable candidate by the EAC.
Exclusion criteria
1. Diagnosis/suspicion of secondary or atypical parkinsonism 2. Previous procedure or surgery for PD, or anticipation of these during the study 3. High likelihood of needing anti-parkinsonian treatment over the study period, in the opinion of the investigator 4. Clinically significant orthostatic hypotension 5. Clinically significant hallucinations requiring antipsychotic use in the 12 months prior to Screening 6. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in the judgement of the treating investigator or the EAC Prior/Concomitant Therapy: 1. Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors, supplements containing levodopa (i.e. Mucana pruriens), or A2A antagonists for more than 28 days, or treatment with any of these medications or supplements within 28 days prior to screening 2. 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 3. Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or CYP3A4/5 inhibitors (except for topical administration) 4. Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine. Prior/Concurrent Clinical Study Experience: 1. Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening 2. Previous randomization into this or another IkT-148009 study Diagnostic Assessments: 1. 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) 2. Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria 3. Medical or recreational use of marijuana in the 3 months prior to the screening visit 4. Any social or behavioral reason that would preclude completion of the study, in the judgement of the investigator 5. Any skin condition that would interfere with obtaining adequate samples 6. Evidence of advanced, age-related macular degeneration (neovascular or geographic atrophy) or intermediate macular degeneration as defined by Beckman classification (Large drusen \> 125 um and/or any AMD pigmentary abnormalities). Evidence of retina/choroid neovascularization from any cause. Evidence of central serous retinopathy. 7. Abnormal amylase and/or lipase at screening (may be repeated during screening period) 8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN) 9. Significant renal impairment as determined by the following criteria: * Creatinine clearance (CrCL) less than or equal to 60 mL/min for subjects \< 65 years of age * Creatine clearance (CrCL) greater than or equal to 55 mL/min and the absence of proteinuria or hematuria for subjects ≥ 65 years of age 10. Currently lactating, pregnant or planning on becoming pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAEs) | Baseline to 12 weeks |
| Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event | Baseline to 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Patient Global Impression - Severity (PGI-S) is participant reported assessment designed to evaluate the severity of their Parkinson's Disease. Scores range from 1 to 4 with 1 considered Normal and 4 considered Severe. |
| LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Clinician Global Impression - Severity (CGI-S) is clinician reported assessment designed to evaluate the severity of a participants Parkinson's disease. Scores range from 1 to 7 with 1 considered Normal and 7 considered Among the most extremely ill patients. |
| LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures | Baseline to 12 weeks | Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part II assesses activities of daily living as reported by the participant. Part II consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease. |
| LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures | Baseline to 12 weeks | Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part III is completed by clinician and assesses a participants motor function. Part III consists of 18 items with a total score ranging from 0 to 132. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease. |
| LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part I assesses non-motor experiences of daily living. Part I is made up of two section with one rated by the investigator and another completed by the participant. Part I consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease. |
| LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Non-Motor Symptom Score (NMSS) is a 30 question assessment completed by the clinician designed to evaluate the non-motor symptoms of Parkinson's disease. Scores range from 0 to 360 with higher scores reflect increasing severity of disease |
| LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures | Baseline to Week 12 | Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Parts II and III reflect assessments covering activites of daily living as reported by the participant (Part II) as well as a clinicians assessment of motor abilities (Part III). Part II consists of 13 items with total scores ranging from 0 to 52 while Part III consists of 18 items with total scores range from 0 to 132. Each item is scored 0 (normal) to 4 (severe). The sum of Parts 2 and 3 have a score range of 0 to 184 (31 total items). An increase in sum of Parts 2 and 3 relative to baseline represents a worsening of the participant's Parkinson's disease |
| LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | The Epworth Sleepiness Scale is a self-administered questionnaire that measures a participant's general level of daytime sleepiness. Participants rate their likelihood of dozing off or falling asleep in eight common situations using a 4-point scale from 0 = would never doze to 3 = high chance of dozing. The total ESS score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness. |
| LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Schwab and England Activies of Daily Living (SE-ADL) is a clinician administered assessment whereby participants assess their ability to complete routine daily activities on a scale from 0 to 100. The score is reported in increments of 10 with 100 representing normal ability to complete daily activities. |
| LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | The Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) is a participant-reported questionnaire designed to assess the severity of upper gastrointestinal symptoms over the previous two weeks. The instrument includes 20 items. Each item is rated on a 6-point Likert scale from 0 = none to 5 = very severe, with higher scores indicating greater symptom severity. A total score is calculated as the mean of non-missing item responses. |
| LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | The Patient Assessment of Constipation Quality of Life (PAC-QOL) is a participant-reported questionnaire that evaluates the impact of constipation and its treatment on quality of life over the previous two weeks. It consists of 28 items. Each item is rated on a 5-point Likert scale from 0 = not at all / very satisfied to 4 = extremely / very dissatisfied, depending on item phrasing. Scores are calculated as the mean of all non-missing items, with higher scores indicating greater negative impact on quality of life. |
| LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | The Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QOL) is a validated, participant-reported questionnaire that assesses the impact of upper gastrointestinal symptoms on quality of life over the previous two weeks. The instrument includes 30 items. Each item is rated on a 6-point Likert scale from 0 = none of the time to 5 = all of the time. Scores are calculated as the mean of all non-missing items, with lower scores represent a greater negative impact on a participant's quality of life. |
| LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | The Complete Spontaneous Bowel Movement (CSBM) Diary is a participant-completed paper diary used to record bowel movement activity over a 7-day period. Each entry captures the date and time of the bowel movement, stool consistency (Bristol Stool Form Scale), and whether the bowel movement was spontaneous (no laxative or rescue medication within the previous 24 hours) and complete (a sensation of full evacuation). The weekly CSBM score is calculated as the total number of complete and spontaneous bowel movements recorded during the 7-day period. Rome IV criteria defines constipation as having less than 3 CSBMs per 7 day period. A decrease in CSBM score represents a decrease in bowel function. |
| LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures | Change from Baseline to Week 12 | Parkinson's Disease Questionnaire (PDQ) consists of 39 questions evaluating activities of daily living. Participants rate each question on a 5 point scale (0 to 4), . The PDQ-39 score ranges from 0 to 100 with higher score representing more advanced disease. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 32 clinical sites in the United States including both private clinics and public institutions. A total of 137 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| 50mg IkT-148009 (Risvodetinib) This arm consisted of participants treated with the 50mg dose of risvodetinib for 12 weeks. | 35 |
| 100mg IkT-148009 (Risvodetinib) This arm consisted of participants treated with the 100mg dose of risvodetinib for 12 weeks. | 34 |
| 200mg IkT-148009 (Risvodetinib) This arm consisted of participants treated with the 200mg dose of risvodetinib for 12 weeks. | 33 |
| Placebo This arm will consist participants treated with placebo for 12 weeks. | 35 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Subjects Withdrawn due to regulatory hold | 3 | 2 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | 100mg IkT-148009 (Risvodetinib) | 200mg IkT-148009 (Risvodetinib) | 50mg IkT-148009 (Risvodetinib) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 8.08 | 63.2 years STANDARD_DEVIATION 7.41 | 63.4 years STANDARD_DEVIATION 7.79 | 64.9 years STANDARD_DEVIATION 7.2 | 63.7 years STANDARD_DEVIATION 7.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 6 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 33 Participants | 29 Participants | 29 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Hoehn & Yahr H&Y 1.0 | 9 Participants | 2 Participants | 13 Participants | 8 Participants | 32 Participants |
| Hoehn & Yahr H&Y 1.5 | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 6 Participants |
| Hoehn & Yahr H&Y 2.0 | 21 Participants | 27 Participants | 20 Participants | 25 Participants | 93 Participants |
| Hoehn & Yahr H&Y 2.5 | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Hoehn & Yahr Missing | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 31 Participants | 32 Participants | 32 Participants | 34 Participants | 129 Participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 12 Participants | 16 Participants | 55 Participants |
| Sex: Female, Male Male | 18 Participants | 22 Participants | 23 Participants | 19 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 34 | 0 / 33 | 0 / 35 |
| other Total, other adverse events | 19 / 35 | 21 / 34 | 21 / 33 | 21 / 35 |
| serious Total, serious adverse events | 1 / 35 | 0 / 34 | 1 / 33 | 1 / 35 |
Outcome results
Primary
Incidence of Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | Incidence of Treatment-emergent Adverse Events (TEAEs) | 19 Participants |
| 100mg IkT-148009 (Risvodetinib) | Incidence of Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
| 200mg IkT-148009 (Risvodetinib) | Incidence of Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | 21 Participants |
Primary
Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event | 1 Participants |
| 100mg IkT-148009 (Risvodetinib) | Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event | 0 Participants |
| 200mg IkT-148009 (Risvodetinib) | Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event | 1 Participants |
| Placebo | Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event | 1 Participants |
Secondary
LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures
Clinician Global Impression - Severity (CGI-S) is clinician reported assessment designed to evaluate the severity of a participants Parkinson's disease. Scores range from 1 to 7 with 1 considered Normal and 7 considered Among the most extremely ill patients.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures | -0.08 score on a scale |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures | 0.13 score on a scale |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures | -0.02 score on a scale |
| Placebo | LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures | 0.11 score on a scale |
Comparison: Change relative to placebo at 12 week of dosingp-value: 0.17895% CI: [-0.488, 0.092]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.93195% CI: [-0.274, 0.3]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.3895% CI: [-0.426, 0.163]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures
The Complete Spontaneous Bowel Movement (CSBM) Diary is a participant-completed paper diary used to record bowel movement activity over a 7-day period. Each entry captures the date and time of the bowel movement, stool consistency (Bristol Stool Form Scale), and whether the bowel movement was spontaneous (no laxative or rescue medication within the previous 24 hours) and complete (a sensation of full evacuation). The weekly CSBM score is calculated as the total number of complete and spontaneous bowel movements recorded during the 7-day period. Rome IV criteria defines constipation as having less than 3 CSBMs per 7 day period. A decrease in CSBM score represents a decrease in bowel function.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures | -0.04 Number of bowel movements per week |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures | 0.30 Number of bowel movements per week |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures | -0.11 Number of bowel movements per week |
| Placebo | LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures | 0.85 Number of bowel movements per week |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.17395% CI: [-2.193, 0.4]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.39395% CI: [-1.828, 0.725]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.14195% CI: [-2.246, 0.323]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures
The Epworth Sleepiness Scale is a self-administered questionnaire that measures a participant's general level of daytime sleepiness. Participants rate their likelihood of dozing off or falling asleep in eight common situations using a 4-point scale from 0 = would never doze to 3 = high chance of dozing. The total ESS score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures | -0.46 Assessment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures | -0.30 Assessment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures | -0.76 Assessment Score |
| Placebo | LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures | -0.68 Assessment Score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.70495% CI: [-0.925, 1.366]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.50695% CI: [-0.742, 1.494]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.88895% CI: [-1.227, 1.063]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part I assesses non-motor experiences of daily living. Part I is made up of two section with one rated by the investigator and another completed by the participant. Part I consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures | -0.93 Assesment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures | -1.03 Assesment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures | 0.22 Assesment Score |
| Placebo | LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures | -0.26 Assesment Score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.29795% CI: [-1.952, 0.602]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.23395% CI: [-2.032, 0.5]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.46495% CI: [-0.818, 1.783]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part II assesses activities of daily living as reported by the participant. Part II consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.
Time frame: Baseline to 12 weeks
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures | 0.11 Scale score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures | -0.32 Scale score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures | -0.08 Scale score |
| Placebo | LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures | 1.09 Scale score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.14495% CI: [-2.308, 0.342]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.03695% CI: [-2.72, -0.096]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.08995% CI: [-2.514, 0.18]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part III is completed by clinician and assesses a participants motor function. Part III consists of 18 items with a total score ranging from 0 to 132. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.
Time frame: Baseline to 12 weeks
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures | -0.04 Assessment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures | 2.14 Assessment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures | 2.20 Assessment Score |
| Placebo | LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures | -0.21 Assessment Score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.91695% CI: [-3.127, 3.477]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.15895% CI: [-0.921, 5.621]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.15795% CI: [-0.941, 5.768]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Parts II and III reflect assessments covering activites of daily living as reported by the participant (Part II) as well as a clinicians assessment of motor abilities (Part III). Part II consists of 13 items with total scores ranging from 0 to 52 while Part III consists of 18 items with total scores range from 0 to 132. Each item is scored 0 (normal) to 4 (severe). The sum of Parts 2 and 3 have a score range of 0 to 184 (31 total items). An increase in sum of Parts 2 and 3 relative to baseline represents a worsening of the participant's Parkinson's disease
Time frame: Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures | 0.08 Score on the Scale |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures | 1.82 Score on the Scale |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures | 2.12 Score on the Scale |
| Placebo | LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures | 0.85 Score on the Scale |
Comparison: Change relative to placebo from baseline to 12 weeks of treatmentp-value: 0.68695% CI: [-4.522, 2.985]Mixed Models Analysis
Comparison: Change relative to placebo from baseline to 12 weeks of treatmentp-value: 0.60695% CI: [-2.745, 4.687]Mixed Models Analysis
Comparison: Change relative to placebo from baseline to 12 weeks of treatmentp-value: 0.50995% CI: [-2.539, 5.086]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures
Non-Motor Symptom Score (NMSS) is a 30 question assessment completed by the clinician designed to evaluate the non-motor symptoms of Parkinson's disease. Scores range from 0 to 360 with higher scores reflect increasing severity of disease
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures | 0.14 Assessment score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures | 0.79 Assessment score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures | 0.88 Assessment score |
| Placebo | LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures | -0.14 Assessment score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.94395% CI: [-7.346, 7.898]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.80695% CI: [-6.547, 8.402]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.79495% CI: [-6.686, 8.719]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures
The Patient Assessment of Constipation Quality of Life (PAC-QOL) is a participant-reported questionnaire that evaluates the impact of constipation and its treatment on quality of life over the previous two weeks. It consists of 28 items. Each item is rated on a 5-point Likert scale from 0 = not at all / very satisfied to 4 = extremely / very dissatisfied, depending on item phrasing. Scores are calculated as the mean of all non-missing items, with higher scores indicating greater negative impact on quality of life.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures | -0.03 Assessment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures | -0.17 Assessment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures | -0.13 Assessment Score |
| Placebo | LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures | -0.03 Assessment Score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.9595% CI: [-0.199, 0.212]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.18995% CI: [-0.338, 0.067]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.37495% CI: [-0.301, 0.114]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures
The Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QOL) is a validated, participant-reported questionnaire that assesses the impact of upper gastrointestinal symptoms on quality of life over the previous two weeks. The instrument includes 30 items. Each item is rated on a 6-point Likert scale from 0 = none of the time to 5 = all of the time. Scores are calculated as the mean of all non-missing items, with lower scores represent a greater negative impact on a participant's quality of life.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures | 0.07 Assessment score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures | 0.06 Assessment score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures | 0.06 Assessment score |
| Placebo | LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures | 0.05 Assessment score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.80395% CI: [-0.101, 0.131]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.93595% CI: [-0.11, 0.12]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.96895% CI: [-0.116, 0.121]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures
The Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) is a participant-reported questionnaire designed to assess the severity of upper gastrointestinal symptoms over the previous two weeks. The instrument includes 20 items. Each item is rated on a 6-point Likert scale from 0 = none to 5 = very severe, with higher scores indicating greater symptom severity. A total score is calculated as the mean of non-missing item responses.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures | -0.04 Assessment score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures | -0.02 Assessment score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures | -0.09 Assessment score |
| Placebo | LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures | 0.05 Assessment score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.32195% CI: [-0.283, 0.094]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.44495% CI: [-0.259, 0.114]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.15495% CI: [-0.332, 0.053]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures
Parkinson's Disease Questionnaire (PDQ) consists of 39 questions evaluating activities of daily living. Participants rate each question on a 5 point scale (0 to 4), . The PDQ-39 score ranges from 0 to 100 with higher score representing more advanced disease.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures | -1.90 Assessment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures | -0.99 Assessment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures | -1.89 Assessment Score |
| Placebo | LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures | -2.35 Assessment Score |
Comparison: Change relative to placebo after 12 weeks of treatmentp-value: 0.68395% CI: [-1.717, 2.611]Mixed Models Analysis
Comparison: Change relative to placebo after 12 weeks of treatmentp-value: 0.21295% CI: [-0.783, 3.495]Mixed Models Analysis
Comparison: Change relative to placebo after 12 weeks of treatmentp-value: 0.68595% CI: [-1.749, 2.654]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures
Patient Global Impression - Severity (PGI-S) is participant reported assessment designed to evaluate the severity of their Parkinson's Disease. Scores range from 1 to 4 with 1 considered Normal and 4 considered Severe.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures | 0.04 score on a scale |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures | 0.13 score on a scale |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures | 0.03 score on a scale |
| Placebo | LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures | -0.04 score on a scale |
Comparison: Change relative to placebo at 12 weeks of treatmentp-value: 0.46395% CI: [-0.139, 0.304]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.13395% CI: [-0.051, 0.383]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.57595% CI: [-0.159, 0.286]Mixed Models Analysis
Secondary
LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures
Schwab and England Activies of Daily Living (SE-ADL) is a clinician administered assessment whereby participants assess their ability to complete routine daily activities on a scale from 0 to 100. The score is reported in increments of 10 with 100 representing normal ability to complete daily activities.
Time frame: Change from Baseline to Week 12
Population: The mITT population will include all randomized participants who have a valid baseline MDS-UPDRS, received at least one dose of study drug, and have at least one post-baseline evaluation of the MDS-UPDRS assessment as defined in the Statistical Analysis Plan
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 50mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures | 0.02 Assessment Score |
| 100mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures | -0.00 Assessment Score |
| 200mg IkT-148009 (Risvodetinib) | LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures | -0.00 Assessment Score |
| Placebo | LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures | -0.02 Assessment Score |
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.00495% CI: [0.013, 0.067]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.12595% CI: [-0.006, 0.047]Mixed Models Analysis
Comparison: Change relative to placebo at 12 weeks of dosingp-value: 0.17995% CI: [-0.009, 0.046]Mixed Models Analysis