Parkinson Disease
Conditions
Keywords
Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Parkinson's Disease, Dementia, Movement Disorder, Shaking Palsy
Brief summary
This study will evaluate the efficacy and safety of AKST4290 in subjects with Parkinson's Disease who are currently on stable dopaminergic treatment.
Interventions
DRUGAKST4290
Oral AKST4290
DRUGPlacebo
Oral Placebo
Sponsors
Alkahest, Inc.
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 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of clinically established or clinically probable PD according to MDS-PD criteria with at least 1 year of PD symptoms. * Modified Hoehn and Yahr ≤2.5. * Have notable motor worsening during off-medication state. * Clear-cut improvement of motor response to levodopa medications, as assessed by the investigator. * Must be on stable dopaminergic therapy (e.g., levodopa, dopamine agonists, monoamine oxidase inhibitors, catechol-O-methyl transferase inhibitors, amantadine), for at least 8 weeks prior to enrollment and remain on stable dose during the 12-week treatment period. * Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening. WOCBP must agree to use highly effective contraception prior to study entry. Male subjects must be willing to use a barrier method of contraception. Key
Exclusion criteria
* Secondary or atypical parkinsonian syndromes, for example, patients with parkinsonism from encephalitis, metabolic disorders, vascular parkinsonism, drug-induced parkinsonism, multiple system atrophy, corticobasal ganglia degeneration, progressive supranuclear palsy, Lewy body dementia. * History of any brain surgery for PD (e.g., pallidotomy, deep brain stimulation, or fetal tissue transplant). * Conditions affecting the peripheral or central nervous system, unless related to PD, that would affect the ability to adequately perform the MDS-UPDRS and motor assessments: i.e., severe sensory neuropathy affecting arm or leg function, or stroke affecting motor or gait function. * Significant alcohol or drug abuse within past 2 years. * Based on ECG reading, subjects with a risk of QT prolongation. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Motor Function During Levodopa Withdrawal. | Baseline to 12 weeks | Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part 3 Motor Examination has 33 scores based on 18 questions with several right, left, or both body distribution scores. Each Parkinsonian sign or symptom is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment. The minimum score on the MDS-UPDRS Part 3 is 0 and the maximum is 132. Outcome is the mean change from Baseline in motor function during the practically defined off-medication state, defined as at least 12 hours off levodopa, at Week 12, with lower score representing better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Laboratory Changes. | Baseline to week 14 | Incidence of of abnormalities or clinically significant changes from Baseline in laboratory test data (chemistry, hematology, coagulation, and urinalysis). Incidence was presented as number of subjects abnormal labs indicating serious condition occurred within the analysis population throughout study duration. |
| Evaluation of Vital Sign Changes. | Baseline to week 12 | Incidence of abnormalities or clinically-significant changes from Baseline in Vital sign measurements (blood pressure as measured in mmHg, heart rate as measured in beats per minute, and temperature as measured in degrees Fahrenheit or Celsius). Incidence was presented as number of subjects with abnormalities or clinically-significant changes from Baseline in Vital sign measurements within the analysis group throughout study duration. |
| Evaluation of Electrocardiogram Changes. | Baseline to week 12 | Incidence of abnormalities or clinically-significant changes from Baseline in 12-lead electrocardiogram (ECG) QT-interval. Incidence was presented as number of subject with ECG changes throughout study duration. |
| The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | Baseline to week 12 | The MDS-UPDRS has 4 components (details below). The rating for each item is from 0 (normal) to 4 (severe). The score for each Part is obtained from the sum of the corresponding item scores, with higher scores indicating more severe impairment. Part I, Non-Motor Aspects (Mentation, Behavior, and Mood) of Experiences of Daily Living (13 items), score range is 0-52. Part II, Motor Aspects of Experiences of Daily Living (13 items), score range is 0-52. Part III, Motor Examination (33 items), score range is 0-132. Part IV, Motor Complications (6 items), score range is 0-24. The outcome is the mean change from Baseline motor function during the on-medication state at Week 12, with lower value representing a better outcome. |
| The Montreal Cognitive Assessment (MoCA), Change From Baseline in MoCA During the On-medication State. | Baseline to week 12 | The Montreal Cognitive Assessment (MoCA) is a neuropsychological tool that requires approximately 15 minutes to assess the following domains: attention, executive function, memory, language, visuoconstructional skills, and orientation. MoCA scores range between 0 and 30, with higher scores indicating more intact cognition. The MoCA is administered at Baseline and Week 12 in the on-medication state. The total score will be summarized at each scheduled time point. The outcome is mean change from baseline in MoCA during the on-medication state at Week 12, with higher value representing a better outcome. |
| Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Baseline to week 14 | Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs, grouped by severity, relationship to study treatment, and AEs leading to discontinuation of study participation. Incidence was presented as number of subject with TEAEs and serious TEAEs, grouped by severity, relationship to study treatment, and AEs leading to discontinuation of study participation, throughout study duration. |
| The Clinical Impression of Severity Index - PD (CISI-PD), Change From Baseline in CISI-PD During the On-medication State. | Baseline to week 12 | The CISI-PD is a severity index formed by four items (motor signs, disability, motor complications, and cognitive status), rated 0 (not at all) to 6 (very severe or completely disabled). A total score is calculated by summing the item scores, total scores range from 0-24. The outcome is the mean change from baseline in CISI-PD during the on-medication state at Week 12, with lower score represents a better outcome. |
| The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Baseline to week 12 | The PDQ-39 is a patient-reported outcome of 39 questions relating to 8 key areas of health and daily activities, including both motor and non-motor symptoms. The eight dimensions include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. It is scored on a scale of 0-100 with lower scores indicating better health and high scores indicating more severe symptoms, applying to all dimensions reported in the data table. Outcome is the mean change from baseline in PDQ-39 during the on-medication state at Week 12, with lower score represents a better outcome. |
| The Sheehan-Suicidality Tracking Scale (S-STS), Change From Baseline in S-STS During the On-medication State. | Baseline to week 12 | The standard version of the S-STS is a 16-item scale that assesses the seriousness of suicidality phenomena on a Likert-type scale (0-4) ranging from not at all (0) to extremely (4), where higher scores indicate more risk of suicidality. It also assesses the frequency of key phenomena and the overall time spent in suicidality. Total score is a sum of all items; total score ranges from 0-64. Outcome is the mean change from baseline in S-STS during the on-medication state at Week 12, with higher score represents a worse outcome. |
| 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Baseline to week 12 | The 10-meter walk test is a commonly used tool for assessing gait speed in individuals with gait limitations. Gait speed is positively correlated with the amount of community ambulation and quality of life, and it is an important measure of mobility in individuals with PD, with higher value corresponds to better mobility. Outcome is the mean change from baseline comfortable walking speed (gait), fast walking speed (gait), during the on and off-medication state at Week 12, with higher score represents a better outcome. |
| Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary | Baseline to week 12 | The Hauser Patient Diary was developed to assess functional status over a period of time in patients with motor fluctuations and dyskinesia by recording patient motor state for half-hour intervals over a 24-hour period. The outcome is mean change of Mean Time Spent with and without troublesome dyskinesia from Baseline at Week 12. ON/OFF-time is time when medication is providing/not providing benefit with regard to mobility, slowness, and stiffness, respectively. Troublesome dyskinesia is defined as dyskinesia that interfere with function or causes meaningful discomfort. Bad time is defined as the sum of off time and on time with troublesome dyskinesia. Lower value represents a better outcome. Good time is defined as the on time without dyskinesia plus on time with non-troublesome dyskinesia. Higher value represents a better outcome. |
| The Schwab and England Activities of Daily Living (SE-ADL) Scale, Change From Baseline in SE-ADL During the On-medication State. | Baseline to week 12 | The SE-ADL evaluates patients' perceptions of global functional capacity and dependence. Scoring is expressed in terms of percentage, in 10 steps from 100 to 0 (100% indicates completely independent, 0% indicates bedridden with impaired vegetative functions), so that the lower the score, the worse the functional status. Scores will be summarized descriptively at each scheduled time point (i.e. n, %) by treatment group. A Generalized Estimating Equations (GEE) for alternating logistic regression (ALR) with an exchangeable working correlation structure will be employed to analyze change from baseline. Outcome is mean change from baseline in SE-ADL during the on-medication state at Week 12, with higher values represents a better outcome. |
Countries
Estonia, Germany, Poland, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AKST4290 Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks.
AKST4290: Oral AKST4290 | 55 |
| Placebo Subjects will receive placebo, twice daily, for 12 weeks.
Placebo: Oral Placebo | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | COVID concern, Sponsor's decision | 2 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | AKST4290 |
|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 7.45 | 64.9 years STANDARD_DEVIATION 6.74 | 63.1 years STANDARD_DEVIATION 8.07 |
| Baseline BMI | 28.02 (kg/m^2) STANDARD_DEVIATION 4.689 | 27.91 (kg/m^2) STANDARD_DEVIATION 4.417 | 28.12 (kg/m^2) STANDARD_DEVIATION 4.986 |
| Disease Duration | 6.69 years STANDARD_DEVIATION 4.571 | 7.62 years STANDARD_DEVIATION 5.467 | 5.71 years STANDARD_DEVIATION 3.138 |
| Education Grade School | 57 Participants | 27 Participants | 30 Participants |
| Education Masters | 18 Participants | 9 Participants | 9 Participants |
| Education PhD/Medical School | 2 Participants | 0 Participants | 2 Participants |
| Education University | 33 Participants | 19 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 55 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Modified Hoehn and Yahr Bilateral disease, without impairment of balance | 64 Participants | 32 Participants | 32 Participants |
| Modified Hoehn and Yahr Mild bilateral disease, with recovery on pull test | 25 Participants | 12 Participants | 13 Participants |
| Modified Hoehn and Yahr No signs of disease | 0 Participants | 0 Participants | 0 Participants |
| Modified Hoehn and Yahr Unilateral disease | 10 Participants | 5 Participants | 5 Participants |
| Modified Hoehn and Yahr Unilateral plus axial involvement | 11 Participants | 6 Participants | 5 Participants |
| Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part 3 in the off-medication state | 36.9 score on a scale STANDARD_DEVIATION 13.35 | 38.5 score on a scale STANDARD_DEVIATION 12.44 | 35.2 score on a scale STANDARD_DEVIATION 14.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 107 Participants | 53 Participants | 54 Participants |
| Sex: Female, Male Female | 42 Participants | 21 Participants | 21 Participants |
| Sex: Female, Male Male | 68 Participants | 34 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 52 | 0 / 55 |
| other Total, other adverse events | 8 / 52 | 11 / 55 |
| serious Total, serious adverse events | 1 / 52 | 3 / 55 |
Outcome results
Primary
Change in Motor Function During Levodopa Withdrawal.
Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part 3 Motor Examination has 33 scores based on 18 questions with several right, left, or both body distribution scores. Each Parkinsonian sign or symptom is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment. The minimum score on the MDS-UPDRS Part 3 is 0 and the maximum is 132. Outcome is the mean change from Baseline in motor function during the practically defined off-medication state, defined as at least 12 hours off levodopa, at Week 12, with lower score representing better outcome.
Time frame: Baseline to 12 weeks
Population: Modified Intent-to-Treat/Evaluables (Subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AKST4290 | Change in Motor Function During Levodopa Withdrawal. | -4.210 score on a scale | Standard Error 1.1844 |
| Placebo | Change in Motor Function During Levodopa Withdrawal. | -5.114 score on a scale | Standard Error 1.1839 |
Secondary
10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State
The 10-meter walk test is a commonly used tool for assessing gait speed in individuals with gait limitations. Gait speed is positively correlated with the amount of community ambulation and quality of life, and it is an important measure of mobility in individuals with PD, with higher value corresponds to better mobility. Outcome is the mean change from baseline comfortable walking speed (gait), fast walking speed (gait), during the on and off-medication state at Week 12, with higher score represents a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AKST4290 | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Comfortable Walking Speed (On-medication) | 0.030 m/s | Standard Error 0.0293 |
| AKST4290 | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Comfortable Walking Speed (Off-medication) | 0.091 m/s | Standard Error 0.0326 |
| AKST4290 | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Fast Walking Speed (Off-medication) | 0.107 m/s | Standard Error 0.0413 |
| AKST4290 | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Fast Walking Speed (On-medication) | 0.041 m/s | Standard Error 0.0405 |
| Placebo | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Fast Walking Speed (On-medication) | 0.075 m/s | Standard Error 0.0407 |
| Placebo | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Comfortable Walking Speed (Off-medication) | 0.084 m/s | Standard Error 0.0329 |
| Placebo | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Comfortable Walking Speed (On-medication) | 0.041 m/s | Standard Error 0.0295 |
| Placebo | 10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State | Fast Walking Speed (Off-medication) | 0.150 m/s | Standard Error 0.0417 |
Secondary
Evaluation of Electrocardiogram Changes.
Incidence of abnormalities or clinically-significant changes from Baseline in 12-lead electrocardiogram (ECG) QT-interval. Incidence was presented as number of subject with ECG changes throughout study duration.
Time frame: Baseline to week 12
Population: Safety Population (all subjects who received at least one dose of the study medication)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKST4290 | Evaluation of Electrocardiogram Changes. | Normal | 35 Participants |
| AKST4290 | Evaluation of Electrocardiogram Changes. | Abnormal, Not Clinically Significant | 10 Participants |
| AKST4290 | Evaluation of Electrocardiogram Changes. | Abnormal, Clinically Significant | 0 Participants |
| Placebo | Evaluation of Electrocardiogram Changes. | Normal | 26 Participants |
| Placebo | Evaluation of Electrocardiogram Changes. | Abnormal, Not Clinically Significant | 16 Participants |
| Placebo | Evaluation of Electrocardiogram Changes. | Abnormal, Clinically Significant | 5 Participants |
Secondary
Evaluation of Laboratory Changes.
Incidence of of abnormalities or clinically significant changes from Baseline in laboratory test data (chemistry, hematology, coagulation, and urinalysis). Incidence was presented as number of subjects abnormal labs indicating serious condition occurred within the analysis population throughout study duration.
Time frame: Baseline to week 14
Population: Safety Population (all subjects who received at least one dose of the study medication).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AKST4290 | Evaluation of Laboratory Changes. | Abnormal Blood Chemistry Labs | 18 Participants |
| AKST4290 | Evaluation of Laboratory Changes. | Abnormal Hematology Labs | 2 Participants |
| AKST4290 | Evaluation of Laboratory Changes. | Abnormal Urinalysis Labs | 0 Participants |
| AKST4290 | Evaluation of Laboratory Changes. | Abnormal Coagulation Labs | 2 Participants |
| Placebo | Evaluation of Laboratory Changes. | Abnormal Coagulation Labs | 4 Participants |
| Placebo | Evaluation of Laboratory Changes. | Abnormal Blood Chemistry Labs | 12 Participants |
| Placebo | Evaluation of Laboratory Changes. | Abnormal Urinalysis Labs | 0 Participants |
| Placebo | Evaluation of Laboratory Changes. | Abnormal Hematology Labs | 1 Participants |
Secondary
Evaluation of Vital Sign Changes.
Incidence of abnormalities or clinically-significant changes from Baseline in Vital sign measurements (blood pressure as measured in mmHg, heart rate as measured in beats per minute, and temperature as measured in degrees Fahrenheit or Celsius). Incidence was presented as number of subjects with abnormalities or clinically-significant changes from Baseline in Vital sign measurements within the analysis group throughout study duration.
Time frame: Baseline to week 12
Population: Safety Population (all subjects who received at least one dose of the study medication); only Abnormal, Clinically Significant incidences were reported in the Outcome Measure Data Table.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKST4290 | Evaluation of Vital Sign Changes. | 0 Participants |
| Placebo | Evaluation of Vital Sign Changes. | 2 Participants |
Secondary
Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary
The Hauser Patient Diary was developed to assess functional status over a period of time in patients with motor fluctuations and dyskinesia by recording patient motor state for half-hour intervals over a 24-hour period. The outcome is mean change of Mean Time Spent with and without troublesome dyskinesia from Baseline at Week 12. ON/OFF-time is time when medication is providing/not providing benefit with regard to mobility, slowness, and stiffness, respectively. Troublesome dyskinesia is defined as dyskinesia that interfere with function or causes meaningful discomfort. Bad time is defined as the sum of off time and on time with troublesome dyskinesia. Lower value represents a better outcome. Good time is defined as the on time without dyskinesia plus on time with non-troublesome dyskinesia. Higher value represents a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AKST4290 | Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary | Mean Bad Time | -1.1 hours | Standard Error 1.06 |
| AKST4290 | Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary | Mean Good time | 1.7 hours | Standard Error 1.24 |
| Placebo | Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary | Mean Bad Time | -1.3 hours | Standard Error 1.06 |
| Placebo | Hauser 3-Day Patient Diary, Change in Baseline Mean Time Spent With and Without Troublesome Dyskinesia as Measured by the Hauser 3-Day Patient Diary | Mean Good time | 0.4 hours | Standard Error 1.24 |
Secondary
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs).
Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs, grouped by severity, relationship to study treatment, and AEs leading to discontinuation of study participation. Incidence was presented as number of subject with TEAEs and serious TEAEs, grouped by severity, relationship to study treatment, and AEs leading to discontinuation of study participation, throughout study duration.
Time frame: Baseline to week 14
Population: Safety Population (all subjects who received at least one dose of the study medication). Subjects with different severity or relationship to study treatment will be counted only once at the highest grade of event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Moderate | 6 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Severe | 1 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Unrelated | 9 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Possibly Related | 10 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Definitely Related | 0 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Unrelated | 1 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Mild | 12 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Severe | 1 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Mild | 0 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Moderate | 0 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Possibly Related | 0 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Definitely Related | 0 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - AEs leading to discontinuation of study participation | 2 participants |
| AKST4290 | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - AEs leading to discontinuation of study participation | 0 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Possibly Related | 0 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Severe | 0 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Severe | 0 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - AEs leading to discontinuation of study participation | 2 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Unrelated | 14 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Mild | 0 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Possibly Related | 11 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Definitely Related | 3 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Relationship to Study Treatment: Definitely Related | 1 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Severity : Moderate | 3 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - Relationship to Study Treatment: Unrelated | 3 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any Serious TEAEs - AEs leading to discontinuation of study participation | 1 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Mild | 17 participants |
| Placebo | Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). | Subjects with any TEAEs - Severity : Moderate | 9 participants |
Secondary
The Clinical Impression of Severity Index - PD (CISI-PD), Change From Baseline in CISI-PD During the On-medication State.
The CISI-PD is a severity index formed by four items (motor signs, disability, motor complications, and cognitive status), rated 0 (not at all) to 6 (very severe or completely disabled). A total score is calculated by summing the item scores, total scores range from 0-24. The outcome is the mean change from baseline in CISI-PD during the on-medication state at Week 12, with lower score represents a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AKST4290 | The Clinical Impression of Severity Index - PD (CISI-PD), Change From Baseline in CISI-PD During the On-medication State. | -0.662 score on a scale | Standard Error 0.2867 |
| Placebo | The Clinical Impression of Severity Index - PD (CISI-PD), Change From Baseline in CISI-PD During the On-medication State. | -0.271 score on a scale | Standard Error 0.2867 |
Secondary
The Montreal Cognitive Assessment (MoCA), Change From Baseline in MoCA During the On-medication State.
The Montreal Cognitive Assessment (MoCA) is a neuropsychological tool that requires approximately 15 minutes to assess the following domains: attention, executive function, memory, language, visuoconstructional skills, and orientation. MoCA scores range between 0 and 30, with higher scores indicating more intact cognition. The MoCA is administered at Baseline and Week 12 in the on-medication state. The total score will be summarized at each scheduled time point. The outcome is mean change from baseline in MoCA during the on-medication state at Week 12, with higher value representing a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AKST4290 | The Montreal Cognitive Assessment (MoCA), Change From Baseline in MoCA During the On-medication State. | 0.0 score on a scale | Standard Error 0.23 |
| Placebo | The Montreal Cognitive Assessment (MoCA), Change From Baseline in MoCA During the On-medication State. | -0.2 score on a scale | Standard Error 0.23 |
Secondary
The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State.
The MDS-UPDRS has 4 components (details below). The rating for each item is from 0 (normal) to 4 (severe). The score for each Part is obtained from the sum of the corresponding item scores, with higher scores indicating more severe impairment. Part I, Non-Motor Aspects (Mentation, Behavior, and Mood) of Experiences of Daily Living (13 items), score range is 0-52. Part II, Motor Aspects of Experiences of Daily Living (13 items), score range is 0-52. Part III, Motor Examination (33 items), score range is 0-132. Part IV, Motor Complications (6 items), score range is 0-24. The outcome is the mean change from Baseline motor function during the on-medication state at Week 12, with lower value representing a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AKST4290 | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 1 | -0.412 score on a scale | Standard Error 0.4581 |
| AKST4290 | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 2 | -0.929 score on a scale | Standard Error 0.4552 |
| AKST4290 | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 4 | -0.130 score on a scale | Standard Error 0.3129 |
| AKST4290 | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 3 | -1.340 score on a scale | Standard Error 1.0729 |
| Placebo | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 4 | -0.160 score on a scale | Standard Error 0.3129 |
| Placebo | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 1 | -0.827 score on a scale | Standard Error 0.4581 |
| Placebo | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 2 | 0.023 score on a scale | Standard Error 0.4552 |
| Placebo | The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 1-4, Change From Baseline During the On-medication State. | MDS-UPDRS Part 3 | -1.300 score on a scale | Standard Error 1.0728 |
Secondary
The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State.
The PDQ-39 is a patient-reported outcome of 39 questions relating to 8 key areas of health and daily activities, including both motor and non-motor symptoms. The eight dimensions include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. It is scored on a scale of 0-100 with lower scores indicating better health and high scores indicating more severe symptoms, applying to all dimensions reported in the data table. Outcome is the mean change from baseline in PDQ-39 during the on-medication state at Week 12, with lower score represents a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Stigma | -6.372 score on a scale | Standard Error 1.491 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Social Support | -3.996 score on a scale | Standard Error 1.7285 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Cognition | -5.415 score on a scale | Standard Error 1.5881 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Activities of Daily Living | -5.557 score on a scale | Standard Error 1.6972 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Communication | -5.736 score on a scale | Standard Error 1.5486 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | PDQ-39 Single Index | -5.649 score on a scale | Standard Error 1.1485 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Bodily Discomfort | -5.660 score on a scale | Standard Error 2.2787 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Emotional Well-Being | -7.299 score on a scale | Standard Error 1.7185 |
| AKST4290 | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Mobility | -5.021 score on a scale | Standard Error 1.8531 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | PDQ-39 Single Index | -3.107 score on a scale | Standard Error 1.1484 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Mobility | -0.744 score on a scale | Standard Error 1.8531 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Activities of Daily Living | -3.022 score on a scale | Standard Error 1.6972 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Emotional Well-Being | -4.602 score on a scale | Standard Error 1.7184 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Social Support | -0.788 score on a scale | Standard Error 1.7285 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Cognition | -5.693 score on a scale | Standard Error 1.5881 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Communication | -1.826 score on a scale | Standard Error 1.5488 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Bodily Discomfort | -5.594 score on a scale | Standard Error 2.2786 |
| Placebo | The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39), Change From Baseline in PDQ-39 During the On-medication State. | Stigma | -2.602 score on a scale | Standard Error 1.4912 |
Secondary
The Schwab and England Activities of Daily Living (SE-ADL) Scale, Change From Baseline in SE-ADL During the On-medication State.
The SE-ADL evaluates patients' perceptions of global functional capacity and dependence. Scoring is expressed in terms of percentage, in 10 steps from 100 to 0 (100% indicates completely independent, 0% indicates bedridden with impaired vegetative functions), so that the lower the score, the worse the functional status. Scores will be summarized descriptively at each scheduled time point (i.e. n, %) by treatment group. A Generalized Estimating Equations (GEE) for alternating logistic regression (ALR) with an exchangeable working correlation structure will be employed to analyze change from baseline. Outcome is mean change from baseline in SE-ADL during the on-medication state at Week 12, with higher values represents a better outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AKST4290 | The Schwab and England Activities of Daily Living (SE-ADL) Scale, Change From Baseline in SE-ADL During the On-medication State. | 1.7 score on a scale | Standard Error 0.91 |
| Placebo | The Schwab and England Activities of Daily Living (SE-ADL) Scale, Change From Baseline in SE-ADL During the On-medication State. | 1.7 score on a scale | Standard Error 0.92 |
Secondary
The Sheehan-Suicidality Tracking Scale (S-STS), Change From Baseline in S-STS During the On-medication State.
The standard version of the S-STS is a 16-item scale that assesses the seriousness of suicidality phenomena on a Likert-type scale (0-4) ranging from not at all (0) to extremely (4), where higher scores indicate more risk of suicidality. It also assesses the frequency of key phenomena and the overall time spent in suicidality. Total score is a sum of all items; total score ranges from 0-64. Outcome is the mean change from baseline in S-STS during the on-medication state at Week 12, with higher score represents a worse outcome.
Time frame: Baseline to week 12
Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AKST4290 | The Sheehan-Suicidality Tracking Scale (S-STS), Change From Baseline in S-STS During the On-medication State. | 0.0 score on a scale | Standard Error 0 |
| Placebo | The Sheehan-Suicidality Tracking Scale (S-STS), Change From Baseline in S-STS During the On-medication State. | 0.0 score on a scale | Standard Error 0 |