Early Parkinson Disease
Conditions
Brief summary
This study consists of 2 parts. Part 1 of the study is conducted to evaluate the efficacy, safety, and tolerability of two doses of K0706 compared to placebo in subjects with early Parkinson's Disease who are not receiving dopaminergic therapy. Part 2 is an optional long term extension study for subjects who have completed week 40 of Part 1
Detailed description
This study is designed to assess the ability of K0706 to slow the progression of PD. Preclinical animal model data have already demonstrated that K0706 has neuroprotective activity, but further development will require human clinical experience. This study will also allow determination of safety and tolerability of K0706 over many months in subjects with PD.
Interventions
DRUGK0706
low dose, orally, once-daily
OTHERplacebo
placebo, orally, once-daily
Sponsors
Sun Pharma Advanced Research Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1: Inclusion criteria: 1. Males or females aged ≥ 50 years; 2. Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2; 3. Diagnosed with Clinically Probable PD according to the MDS clinical diagnostic criteria, with documented diagnosis of PD per treating physician's records within three years of the Screening visit. Disease severity according to modified Hoehn & Yahr stage ≤ 2; 4. Projected to not required to start dopaminergic therapy within 9 months from Baseline;
Exclusion criteria
1. Current, or within 60 days of Screening, use of any prescription, investigational, or over the counter medication for the symptomatic treatment of PD or to slow the progression of PD. Treatment with Monoamine Oxidase B (MAOB) inhibitors will be allowed if the dose is stable for at least 30 days prior to Screening and subjects agree to remain on it for the duration of the study; 2. Prior use of dopaminergic therapy (e.g., levodopa, dopamine agonist, amantadine) for 30 or more days any time in the past; 3. A diagnosis of a significant central or peripheral nervous system disease affecting the subject's cognition or motor function at any time, such as another neurodegenerative disorder, multiple sclerosis or stroke. This does not include transient neurological deficits such as transient ischemic attacks or migraine aura; 4. A diagnosis of a medical condition that could interfere with interpretation of the MDS-UPDRS during the trial (e.g., musculoskeletal disorders); 5. Contraindications to receiving an MRI; 6. Contraindications to receiving a DaT SPECT scan (e.g., hypersensitivity to the active substance, any of the excipients, or iodine) if a new DaT SPECT scan is required for the study; 7. Most recent DaT SPECT scan not compatible with PD (i.e., Scans Without Evidence of Dopaminergic Deficit \[SWEDD\]) based on a central reading by a study physician; 8. MRI of the brain performed after onset of PD suggestive of secondary Parkinsonism (e.g., subdural hematoma, normal pressure hydrocephalus, or infarcts of the basal ganglia); 9. Severe tremors as defined by a score of severe on any of the MDS-UPDRS Parts 2 or 3 tremor severity (not constancy) items; 10. Montreal cognitive assessment score \< 25 11. History of any surgery on the brain itself including deep brain stimulation for PD (note this does not include surgeries on the skull that do not affect the brain, e.g., small meningioma removal); 12. History of hypersensitivity (e.g., bronchospasm, anaphylaxis, serious drug rash) to contents of the study drug or other tyrosine kinase inhibitors; 13. Recent use of medications that can cause Parkinsonism and suspicion of the investigator that it could have worsened the subject's Parkinsonism. This includes neuroleptics (e.g., olanzapine, risperidone, haloperidol), some anti-nausea medications (e.g., prochlorperazine, metoclopramide) and others (e.g., flunarizine, methyldopa) 14. Use of medications that affect the dopaminergic system within 60 days of Screening. This includes stimulants (e.g., methylphenidate, amphetamine derivatives, modafinil) and Monoamine Oxidase A (MAOA) inhibitors (e.g., phenelzine, and tranylcypromine). Note that antidepressants are acceptable as long as the subject has remained on them at a stable dose for over 60 days prior to Screening and plans to remain on them through the study; 15. Any malignant disease (other than basal cell carcinoma of the skin) with evidence of disease within the past 5 years and with the potential for recurrence Part 2: Inclusion criteria: 1. Subject has completed part 1 of the study. 2. Subject projected not to need dopaminergic treatment except for treatment with Monoamine Oxidase B (MAOB) inhibitors. MAOB inhibitors will be allowed if the patient was already taking the same during part 1 of the study. 3. Subject has received K0706/placebo, as appropriate, within 4 weeks prior to end of part 1 of the study. 4. Male subjects enrolled in the study should not father a child and are advised to prevent the passage of semen to their sexual partner during intercourse using an effective method, as judged by the Investigator, for the duration of the study and for 3 months after the last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score. | Week 40 | Part III: Motor examination: 18 items. Score range: 0-132, 32 and below is mild, 59 and above is severe. |
| Number of Participants With Treatment-emergent Adverse Events | Part 2 (Week 40 to 80) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants | Part 1: Week 40 and Part 2: Week 80 (Part 2 is applicable to the subjects who complete the EoT visit of part 1 (V11/Week 40) and who confirm their willingness to participate in part 2 of the study. | — |
| Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 1: Week 40 and Part 2: Week 76 | The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II assesses the motor aspects of experiences of daily living based on patient self-report. It comprises 13 items, each rated on a 5-point scale ranging from 0 (normal) to 4 (severe impairment). The total score for Part II ranges from 0 to 52, calculated as the sum of the individual item scores. The MDS-UPDRS Part III assesses the motor symptoms of Parkinson's disease. This part consists of 18 items, which are assessed across various body regions, resulting in 33 individual scores. Each item is rated on a 5-point scale from 0 (normal) to 4 (severe impairment), with higher scores indicating greater motor dysfunction. The total score for Part III ranges from 0 to 132, which is the sum of the individual item scores. The sum of the MDS-UPDRS Part II and Part III total scores ranges from 0 to 184, with high scores indicating greater clinical impairment. |
| Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version | Week 40 | Health-Related quality of life (HRQoL) will be measured using the European Quality of Life Questionnaire 5 level version (EQ-5D-5L). This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine. |
| Change in Clinician Global Impression Severity | Week 40 | The Clinician Global Impression Severity (CGIS) is a tool used to measure overall disease severity, assessed as follows: 1. Normal 2. Borderline 3. Mild 4. Moderate 5. Marked 6. Severe 7. Among the Most Extremely Ill Patient |
| Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire | Week 40 | The Scales for Outcome in Parkinson's disease - Autonomic (SCOPA-AUT) sum score is a sum of rating scores over 23 items. The SCOPA-AUT sum score ranges from 0 to 69. A higher score means a more severe autonomic dysfunction (i.e., a worse outcome). For each of the 23 items, the score ranges from 0 to 3. The rating scale is the follows: 0= Never experiencing the symptom; 1. Sometimes experiencing the symptom; 2. Regularly experiencing the symptom; 3. Often experiencing the symptom |
| Serum Concentration Level of K0706 | Week 28 | Plasma pharmacokinetic (PK) samples were collected Week 28, per the Schedule of Assessment of the study protocol. There was no PK samples collected after Week 28 per the study protocol. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood K0706 Levels | Week 40 | Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy. |
| Skin Punch Biopsy | Week 40 | Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy. |
| CSF K0706 Levels Progression or Target Engagement of K0706. | Week 40 | Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy. |
| Exploratory Outcome: Effect of K0706 on Dopamine Cell Health in Parkinson's Disease as Detected Via Dopamine Transporter Single Photon Emission Computed Tomography (DaT SPECT) Brain Imaging | Week 40 | Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy. |
| Brain DaT SPECT - an Imaging Tool That is a Marker of Dopaminergic Cell Health. | Week 40 | Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy. |
Countries
Hungary, India, Poland, Slovakia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| K0706, Low Dose K0706: low dose, orally, once-daily This study consists of two parts. Subjects who had been randomized to placebo in Part 1 will be rolled over to a high dose K0706 (384 mg powder for suspension or equivalent formulation) at Week 40. Subjects that had been randomized to either dose of K0706 in part 1 of the study will continue on the same dosing regimen in Part 2 of the study. All subjects will continue treatment for up to 36 weeks. | 171 |
| K0706, High Dose K0706: high dose, orally, once-daily This study consists of two parts. Subjects who had been randomized to placebo in Part 1 will be rolled over to a high dose K0706 (384 mg powder for suspension or equivalent formulation) at Week 40. Subjects that had been randomized to either dose of K0706 in part 1 of the study will continue on the same dosing regimen in Part 2 of the study. All subjects will continue treatment for up to 36 weeks. | 174 |
| Placebo placebo: placebo, orally, once-daily (Prior placebo transitioned to K0706 high-dose) This study consists of two parts. Subjects who had been randomized to placebo in Part 1 will be rolled over to a high dose K0706 (384 mg powder for suspension or equivalent formulation) at Week 40. Subjects that had been randomized to either dose of K0706 in part 1 of the study will continue on the same dosing regimen in Part 2 of the study. All subjects will continue treatment for up to 36 weeks. | 168 |
| Total | 513 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Subject Disposition in Part 1 Period | Adverse Event | 25 | 55 | 12 |
| Subject Disposition in Part 1 Period | Death | 1 | 0 | 0 |
| Subject Disposition in Part 1 Period | Lost to Follow-up | 1 | 3 | 2 |
| Subject Disposition in Part 1 Period | Other | 0 | 2 | 2 |
| Subject Disposition in Part 1 Period | Parkinson's disease progression | 2 | 8 | 5 |
| Subject Disposition in Part 1 Period | Physician Decision | 0 | 3 | 2 |
| Subject Disposition in Part 1 Period | Poor compliance | 0 | 2 | 0 |
| Subject Disposition in Part 1 Period | Protocol Violation | 1 | 1 | 0 |
| Subject Disposition in Part 1 Period | Requires prohibited medication | 4 | 5 | 3 |
| Subject Disposition in Part 1 Period | Study terminated by Sponsor | 12 | 8 | 13 |
| Subject Disposition in Part 1 Period | Withdrawal by Subject | 0 | 5 | 3 |
| Subject Disposition in Part 1 Period | Withdrawal of consent | 11 | 16 | 6 |
| Subject Disposition in Part 2 Period | Adverse Event | 2 | 5 | 12 |
| Subject Disposition in Part 2 Period | Lost to Follow-up | 1 | 0 | 0 |
| Subject Disposition in Part 2 Period | Other | 1 | 0 | 0 |
| Subject Disposition in Part 2 Period | Parkinson's disease progression | 4 | 0 | 2 |
| Subject Disposition in Part 2 Period | Protocol Violation | 1 | 0 | 4 |
| Subject Disposition in Part 2 Period | Requires prohibited medication | 3 | 1 | 5 |
| Subject Disposition in Part 2 Period | Study terminated by Sponsor | 18 | 11 | 13 |
| Subject Disposition in Part 2 Period | Withdrawal by Subject | 1 | 1 | 2 |
| Subject Disposition in Part 2 Period | Withdrawal of consent | 5 | 1 | 12 |
Baseline characteristics
| Characteristic | K0706, Low Dose | K0706, High Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous Part 1 | 64.3 years STANDARD_DEVIATION 8.44 | 65.3 years STANDARD_DEVIATION 7.67 | 65.4 years STANDARD_DEVIATION 8.03 | 65.0 years STANDARD_DEVIATION 8.05 |
| Age, Continuous Part 2 | 62.6 years STANDARD_DEVIATION 7.75 | 65.3 years STANDARD_DEVIATION 6.66 | 66.0 years STANDARD_DEVIATION 7.84 | 64.5 years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Part 1 Hispanic or Latino | 16 Participants | 17 Participants | 15 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Part 1 Not Hispanic or Latino | 154 Participants | 156 Participants | 153 Participants | 463 Participants |
| Ethnicity (NIH/OMB) Part 1 Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Part 2 Hispanic or Latino | 8 Participants | 2 Participants | 4 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Part 2 Not Hispanic or Latino | 64 Participants | 38 Participants | 73 Participants | 175 Participants |
| Ethnicity (NIH/OMB) Part 2 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 1 American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Part 1 Asian | 33 Participants | 29 Participants | 28 Participants | 90 Participants |
| Race (NIH/OMB) Part 1 Black or African American | 6 Participants | 1 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) Part 1 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 1 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 1 White | 132 Participants | 144 Participants | 136 Participants | 412 Participants |
| Race (NIH/OMB) Part 2 American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Part 2 Asian | 19 Participants | 6 Participants | 13 Participants | 38 Participants |
| Race (NIH/OMB) Part 2 Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Part 2 More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 White | 52 Participants | 33 Participants | 63 Participants | 148 Participants |
| Sex: Female, Male Part 1 Female | 61 Participants | 71 Participants | 47 Participants | 179 Participants |
| Sex: Female, Male Part 1 Male | 110 Participants | 103 Participants | 121 Participants | 334 Participants |
| Sex: Female, Male Part 2 Female | 23 Participants | 11 Participants | 20 Participants | 54 Participants |
| Sex: Female, Male Part 2 Male | 49 Participants | 29 Participants | 57 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 117 | 0 / 0 | 1 / 171 | 0 / 173 | 0 / 167 |
| other Total, other adverse events | 21 / 72 | 85 / 117 | 0 / 0 | 131 / 171 | 150 / 173 | 124 / 167 |
| serious Total, serious adverse events | 3 / 72 | 11 / 117 | 0 / 0 | 14 / 171 | 7 / 173 | 5 / 167 |
Outcome results
Primary
Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score.
Part III: Motor examination: 18 items. Score range: 0-132, 32 and below is mild, 59 and above is severe.
Time frame: Week 40
Population: Efficacy analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K0706, Low Dose | Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score. | 1.5 score on a scale | Standard Deviation 8.77 |
| K0706, High Dose | Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score. | 1 score on a scale | Standard Deviation 7.58 |
| Placebo | Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score. | -1 score on a scale | Standard Deviation 8.13 |
Primary
Number of Participants With Treatment-emergent Adverse Events
Time frame: Part 2 (Week 40 to 80)
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K0706, Low Dose | Number of Participants With Treatment-emergent Adverse Events | 37 Participants |
| K0706, High Dose | Number of Participants With Treatment-emergent Adverse Events | 24 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | 61 Participants |
Secondary
Change in Clinician Global Impression Severity
The Clinician Global Impression Severity (CGIS) is a tool used to measure overall disease severity, assessed as follows: 1. Normal 2. Borderline 3. Mild 4. Moderate 5. Marked 6. Severe 7. Among the Most Extremely Ill Patient
Time frame: Week 40
Population: Efficacy analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K0706, Low Dose | Change in Clinician Global Impression Severity | 0.2 score on a scale | Standard Deviation 0.68 |
| K0706, High Dose | Change in Clinician Global Impression Severity | 0.0 score on a scale | Standard Deviation 0.74 |
| Placebo | Change in Clinician Global Impression Severity | 0.2 score on a scale | Standard Deviation 0.91 |
Secondary
Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version
Health-Related quality of life (HRQoL) will be measured using the European Quality of Life Questionnaire 5 level version (EQ-5D-5L). This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.
Time frame: Week 40
Population: Efficacy analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K0706, Low Dose | Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version | -0.0419 score on a scale | Standard Deviation 0.1106 |
| K0706, High Dose | Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version | -0.0531 score on a scale | Standard Deviation 0.16289 |
| Placebo | Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version | -0.0140 score on a scale | Standard Deviation 0.10787 |
Secondary
Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire
The Scales for Outcome in Parkinson's disease - Autonomic (SCOPA-AUT) sum score is a sum of rating scores over 23 items. The SCOPA-AUT sum score ranges from 0 to 69. A higher score means a more severe autonomic dysfunction (i.e., a worse outcome). For each of the 23 items, the score ranges from 0 to 3. The rating scale is the follows: 0= Never experiencing the symptom; 1. Sometimes experiencing the symptom; 2. Regularly experiencing the symptom; 3. Often experiencing the symptom
Time frame: Week 40
Population: Efficacy analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K0706, Low Dose | Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire | 1.6 score on a scale | Standard Deviation 7.7 |
| K0706, High Dose | Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire | 3.8 score on a scale | Standard Deviation 10.11 |
| Placebo | Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire | 0.3 score on a scale | Standard Deviation 7.76 |
Secondary
Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score.
The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II assesses the motor aspects of experiences of daily living based on patient self-report. It comprises 13 items, each rated on a 5-point scale ranging from 0 (normal) to 4 (severe impairment). The total score for Part II ranges from 0 to 52, calculated as the sum of the individual item scores. The MDS-UPDRS Part III assesses the motor symptoms of Parkinson's disease. This part consists of 18 items, which are assessed across various body regions, resulting in 33 individual scores. Each item is rated on a 5-point scale from 0 (normal) to 4 (severe impairment), with higher scores indicating greater motor dysfunction. The total score for Part III ranges from 0 to 132, which is the sum of the individual item scores. The sum of the MDS-UPDRS Part II and Part III total scores ranges from 0 to 184, with high scores indicating greater clinical impairment.
Time frame: Part 1: Week 40 and Part 2: Week 76
Population: Efficacy analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| K0706, Low Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 1 Period: MDS-UPDRS (Sum of Parts II and III Total Scores) | 2.6 score on a scale | Standard Deviation 10.83 |
| K0706, Low Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Rigidity Subscore | 1.7 score on a scale | Standard Deviation 4.46 |
| K0706, Low Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Bradykinesia Subscore | -0.7 score on a scale | Standard Deviation 2.25 |
| K0706, Low Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Axial Symptoms Subscore | 0.5 score on a scale | Standard Deviation 1.22 |
| K0706, Low Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Tremors Subscore | 0.4 score on a scale | Standard Deviation 1.87 |
| K0706, High Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 1 Period: MDS-UPDRS (Sum of Parts II and III Total Scores) | 2.7 score on a scale | Standard Deviation 9.72 |
| K0706, High Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Bradykinesia Subscore | -0.1 score on a scale | Standard Deviation 0.83 |
| K0706, High Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Tremors Subscore | -0.9 score on a scale | Standard Deviation 2.54 |
| K0706, High Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Rigidity Subscore | 0.2 score on a scale | Standard Deviation 3.81 |
| K0706, High Dose | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Axial Symptoms Subscore | 0.4 score on a scale | Standard Deviation 1.15 |
| Placebo | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Axial Symptoms Subscore | 0.0 score on a scale | Standard Deviation 1.37 |
| Placebo | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Rigidity Subscore | 0.8 score on a scale | Standard Deviation 4.12 |
| Placebo | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 1 Period: MDS-UPDRS (Sum of Parts II and III Total Scores) | -0.6 score on a scale | Standard Deviation 9.53 |
| Placebo | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Bradykinesia Subscore | 0.0 score on a scale | Standard Deviation 2.2 |
| Placebo | Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score. | Part 2 Period: MDS-UPDRS Part III Tremors Subscore | -0.4 score on a scale | Standard Deviation 2.68 |
Secondary
Serum Concentration Level of K0706
Plasma pharmacokinetic (PK) samples were collected Week 28, per the Schedule of Assessment of the study protocol. There was no PK samples collected after Week 28 per the study protocol.
Time frame: Week 28
Population: PK Analysis Set (Part 1): The PK Analysis Set (Part 1) included all subjects who received at least one dose of study drug in Part 1 (i.e., the 40-week double-blind part) of the study and also had at least one blood sample taken to measure the K0706 concentration level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| K0706, Low Dose | Serum Concentration Level of K0706 | 1127.8 ng/mL | Standard Deviation 1379.69 |
| K0706, High Dose | Serum Concentration Level of K0706 | 1451.9 ng/mL | Standard Deviation 1371.79 |
Secondary
To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants
Time frame: Part 1: Week 40 and Part 2: Week 80 (Part 2 is applicable to the subjects who complete the EoT visit of part 1 (V11/Week 40) and who confirm their willingness to participate in part 2 of the study.
Population: Efficacy analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| K0706, Low Dose | To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants | 149 Participants |
| K0706, High Dose | To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants | 129 Participants |
| Placebo | To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants | 144 Participants |
Other Pre-specified
Blood K0706 Levels
Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.
Time frame: Week 40
Other Pre-specified
Brain DaT SPECT - an Imaging Tool That is a Marker of Dopaminergic Cell Health.
Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.
Time frame: Week 40
Other Pre-specified
CSF K0706 Levels Progression or Target Engagement of K0706.
Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.
Time frame: Week 40
Other Pre-specified
Exploratory Outcome: Effect of K0706 on Dopamine Cell Health in Parkinson's Disease as Detected Via Dopamine Transporter Single Photon Emission Computed Tomography (DaT SPECT) Brain Imaging
Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.
Time frame: Week 40
Other Pre-specified
Skin Punch Biopsy
Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.
Time frame: Week 40