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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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The goal of this study is to test KM-819 in halting or slowing the progression of Parkinson's disease.
The study evaluates the safety and tolerability of multiple ascending doses of KM-819 in healthy older adults and participants with Parkinson's disease.
The overall study will consist of three parts (Part 1a, Part 1b and Part 2).
Part 1 of this study will evaluate the safety, tolerability and plasma PK of multiple ascending doses (MAD) of KM-819 in healthy older adults (Part 1a) and participants with Parkinson's disease (Part 1b).
Part 2 of the study is a randomized, double-blind, multiple dose study in participants with Parkinson's disease that will include 2 cohorts. It is designed to test the safety, tolerability, plasma PK and pharmacodynamic effects of KM-819 in participants with Parkinson's disease. The study will also assess the degree to which those treated with KM-819 will experience gains in overall daily function within the context of improved Parkinson's disease motor and non-motor symptoms in comparison to placebo. Participants will be randomized to receive KM-819 or matching placebo at doses to be determined based on the findings from Part 1 in a 2:1 ratio.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1a: Cohort 1.1a Dose 400 mg | Experimental | Healthy older adult participants will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
|
| Part 1a: Cohort 1.2a Dose 600 mg | Experimental | Healthy older adult participants will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
|
| Part 1a: Cohort 1.3a Dose 800 mg | Experimental | Healthy older adult participants will receive oral 800 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
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| Part 1b: Cohort 1.1b Dose 200 mg | Experimental | Participants with Parkinson's disease will receive oral 200 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KM-819 | Drug | Participants will receive oral doses of KM-819 once-daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1a,1b and 2: Number of participants with adverse events and serious adverse events | To evaluate the safety and tolerability of multiple ascending doses of KM-819 | Part 1a and Part 1b: From screening (Day -42 to -3) up to 7 days and Part 2: From screening (Day -42 to -2) to 730 days |
| Part 2: Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II: Activities of Daily Living (ADL) Score at Day 730 | Activities of Daily living (ADL) will be assessed via MDS-UPDRS score. MDS-UPDRS Part II is a self-administered questionnaire that assesses the motor experience of daily living in participants with Parkinson's disease. Score: 0: Normal, 1: Slight, 2: Mild, 3: Moderate, 4: Severe. Higher the score, the more severe the condition or symptom | From screening (Day -42 to -2) to Day 730 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1a and 1b: Area under the concentration-time curve (AUC) from pre-dose (time zero) to the time of the last quantifiable concentration AUC(0-t) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: AUC from pre-dose (time zero) to 24 hours post-dose [AUC(0-24)] |
| Measure | Description | Time Frame |
|---|---|---|
| Digital biomarkers using the Parkinson's Disease Digital Biomarker Solutions from Roche Molecular Solutions. | Measurements of active and passive monitoring of Parkinson's disease symptoms utilizing smartphone based devices and software | From screening (Day -42 to -2) to 2 years |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel Early Phase Clinical Unit | Glendale | California | 91206 | United States | ||
| University California San Diego Medical Center |
Individual Identifiable personal information will not be shared. All individuals will be coded.
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000634265 | KM-819 |
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Double-Blinded
| Part 1b: Cohort 1.2b Dose 400 mg | Experimental | Participants with Parkinson's disease will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
|
| Part 1b: Cohort 1.3b Dose 600 mg | Experimental | Participants with Parkinson's disease will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention. |
|
| Part 2: Cohort 2.1 Dose X | Experimental | Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting. |
|
| Part 2: Cohort 2.2 Dose Y | Experimental | Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting. |
|
| Placebo | Drug | Participants will receive matching placebo once-daily |
|
To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma |
| Day 1 |
| Part 1a and 1b: Maximum concentration (Cmax) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Time to achieve Cmax (tmax) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Minimum concentration (Cmin) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: AUC normalized to dose administered (AUC_D) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Cmax normalized to dose administered (Cmax_D) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: AUC from pre-dose (time zero) extrapolated to time infinity [AUC(0-inf)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Apparent terminal elimination half-life (t½) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Terminal elimination rate constant (λz) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Percentage of AUCinf that is extrapolated beyond the time of the last quantifiable concentration [%AUC (extrap)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: Apparent oral clearance (CL/F) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: AUC(0-t) at steady state (Vz/F) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 1 |
| Part 1a and 1b: AUC(0-t) at steady state [AUC(0-t_ss)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: AUCtau at steady state [AUC(tau_ss)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Cmax at steady state (Cmax,ss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: tmax at steady state (tmax,ss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Ctrough at steady state (Ctrough_ss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Minimum concentration at steady state (Cmin,ss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Average observed concentration at steady state (Cav,ss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Accumulation ratio calculated using AUC [Rac (AUC)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Accumulation ratio calculated using Cmax [Rac (Cmax)] | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Apparent oral clearance at steady state (CL/Fss) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: AUC normalized to dose administered at steady state (AUCss_D) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Cmax_ss normalized to dose administered (Cmaxss_D) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in plasma | Day 7 |
| Part 1a and 1b: Fraction of dose excreted in urine (Fe) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine | Day 7 |
| Part 1a and 1b: Renal clearance (CLR) | To evaluate the pharmacokinetics (PK) of multiple ascending doses (MAD) of KM-819 in urine | Day 7 |
| Part 2: Sparse plasma PK blood sampling for population PK analysis | Sparse plasma population PK sampling will be collected, and population PK modeling will be used to characterize the PK of KM-819 in participants with Parkinson's disease. | Day 1, Day 7, Day 30 and Day 180 |
| San Diego |
| California |
| 92103 |
| United States |
| Quest Research Institute, Rose Cancer Center | Royal Oak | Michigan | 48073 | United States |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |