Trial Outcomes & Findings for Study Assessing Efficacy and Safety of AKST4290 in Subjects With Parkinson's Disease on Stable Dopaminergic Treatment (NCT NCT04369430)

NCT ID: NCT04369430

Last Updated: 2022-10-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 110 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2022-10-10

Participant Flow

Participant milestones

Measure	AKST4290 Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Overall Study STARTED	55	55
Overall Study COMPLETED	46	47
Overall Study NOT COMPLETED	9	8

Reasons for withdrawal

Measure	AKST4290 Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Overall Study Adverse Event	2	3
Overall Study Death	1	0
Overall Study Withdrawal by Subject	4	3
Overall Study COVID concern, Sponsor's decision	2	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Disease duration was not captured for 3 subjects who were randomized but not treated.

Baseline characteristics by cohort

Measure	AKST4290 n=55 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=55 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo	Total n=110 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 8.07 • n=55 Participants	64.9 years STANDARD_DEVIATION 6.74 • n=55 Participants	64.0 years STANDARD_DEVIATION 7.45 • n=110 Participants
Sex: Female, Male Female	21 Participants n=55 Participants	21 Participants n=55 Participants	42 Participants n=110 Participants
Sex: Female, Male Male	34 Participants n=55 Participants	34 Participants n=55 Participants	68 Participants n=110 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=55 Participants	55 Participants n=55 Participants	110 Participants n=110 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Race (NIH/OMB) Asian	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Race (NIH/OMB) Black or African American	1 Participants n=55 Participants	1 Participants n=55 Participants	2 Participants n=110 Participants
Race (NIH/OMB) White	54 Participants n=55 Participants	53 Participants n=55 Participants	107 Participants n=110 Participants
Race (NIH/OMB) More than one race	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=55 Participants	1 Participants n=55 Participants	1 Participants n=110 Participants
Education Grade School	30 Participants n=55 Participants	27 Participants n=55 Participants	57 Participants n=110 Participants
Education University	14 Participants n=55 Participants	19 Participants n=55 Participants	33 Participants n=110 Participants
Education Masters	9 Participants n=55 Participants	9 Participants n=55 Participants	18 Participants n=110 Participants
Education PhD/Medical School	2 Participants n=55 Participants	0 Participants n=55 Participants	2 Participants n=110 Participants
Baseline BMI	28.12 (kg/m^2) STANDARD_DEVIATION 4.986 • n=55 Participants	27.91 (kg/m^2) STANDARD_DEVIATION 4.417 • n=55 Participants	28.02 (kg/m^2) STANDARD_DEVIATION 4.689 • n=110 Participants
Disease Duration	5.71 years STANDARD_DEVIATION 3.138 • n=52 Participants • Disease duration was not captured for 3 subjects who were randomized but not treated.	7.62 years STANDARD_DEVIATION 5.467 • n=55 Participants • Disease duration was not captured for 3 subjects who were randomized but not treated.	6.69 years STANDARD_DEVIATION 4.571 • n=107 Participants • Disease duration was not captured for 3 subjects who were randomized but not treated.
Modified Hoehn and Yahr No signs of disease	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=110 Participants
Modified Hoehn and Yahr Unilateral disease	5 Participants n=55 Participants	5 Participants n=55 Participants	10 Participants n=110 Participants
Modified Hoehn and Yahr Unilateral plus axial involvement	5 Participants n=55 Participants	6 Participants n=55 Participants	11 Participants n=110 Participants
Modified Hoehn and Yahr Bilateral disease, without impairment of balance	32 Participants n=55 Participants	32 Participants n=55 Participants	64 Participants n=110 Participants
Modified Hoehn and Yahr Mild bilateral disease, with recovery on pull test	13 Participants n=55 Participants	12 Participants n=55 Participants	25 Participants n=110 Participants
Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part 3 in the off-medication state	35.2 score on a scale STANDARD_DEVIATION 14.17 • n=52 Participants • MDPRS Part 3 in the off-medication state was not captured for 3 subjects who were randomized but not treated.	38.5 score on a scale STANDARD_DEVIATION 12.44 • n=55 Participants • MDPRS Part 3 in the off-medication state was not captured for 3 subjects who were randomized but not treated.	36.9 score on a scale STANDARD_DEVIATION 13.35 • n=107 Participants • MDPRS Part 3 in the off-medication state was not captured for 3 subjects who were randomized but not treated.

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Modified Intent-to-Treat/Evaluables (Subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Change in Motor Function During Levodopa Withdrawal.	-4.210 score on a scale Standard Error 1.1844	-5.114 score on a scale Standard Error 1.1839

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	AKST4290 n=52 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=55 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any TEAEs - Severity : Mild	12 participants	17 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any TEAEs - Severity : Moderate	6 participants	9 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any TEAEs - Severity : Severe	1 participants	0 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any Serious TEAEs - Severity : Mild	0 participants	0 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any Serious TEAEs - Severity : Moderate	0 participants	3 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any Serious TEAEs - Severity : Severe	1 participants	0 participants
Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). Subjects with any TEAEs - Relationship to Study Treatment: Unrelated	9 participants	14 participants
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	11 participants
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	1 participants
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	3 participants
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	0 participants
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	1 participants
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	3 participants
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	2 participants

SECONDARY outcome

Timeframe: Baseline to week 14

Population: Safety Population (all subjects who received at least one dose of the study medication).

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.

Outcome measures

Measure	AKST4290 n=52 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=55 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Evaluation of Laboratory Changes. Abnormal Blood Chemistry Labs	18 Participants	12 Participants
Evaluation of Laboratory Changes. Abnormal Hematology Labs	2 Participants	1 Participants
Evaluation of Laboratory Changes. Abnormal Urinalysis Labs	0 Participants	0 Participants
Evaluation of Laboratory Changes. Abnormal Coagulation Labs	2 Participants	4 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	AKST4290 n=46 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=48 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Evaluation of Vital Sign Changes.	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Safety Population (all subjects who received at least one dose of the study medication)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=47 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Evaluation of Electrocardiogram Changes. Normal	35 Participants	26 Participants
Evaluation of Electrocardiogram Changes. Abnormal, Not Clinically Significant	10 Participants	16 Participants
Evaluation of Electrocardiogram Changes. Abnormal, Clinically Significant	0 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral 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	-0.929 score on a scale Standard Error 0.4552	0.023 score on a scale Standard Error 0.4552
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	-0.160 score on a scale Standard Error 0.3129
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	-1.300 score on a scale Standard Error 1.0728
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	-0.827 score on a scale Standard Error 0.4581

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=43 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=44 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
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	-0.2 score on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral 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 0.91	1.7 score on a scale Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
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	-0.271 score on a scale Standard Error 0.2867

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
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	-0.744 score on a scale Standard Error 1.8531
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 1.4910	-2.602 score on a scale Standard Error 1.4912
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	-0.788 score on a scale Standard Error 1.7285
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	-5.693 score on a scale Standard Error 1.5881
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	-1.826 score on a scale Standard Error 1.5488
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	-5.594 score on a scale Standard Error 2.2786
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	-3.107 score on a scale Standard Error 1.1484
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	-3.022 score on a scale Standard Error 1.6972
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	-4.602 score on a scale Standard Error 1.7184

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral 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 0.00	0.0 score on a scale Standard Error 0.00

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=44 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
10-meter Timed Walk, Change in Baseline 10-meter Timed Walk During the on and Off-medication State Comfortable Walking Speed (Off-medication)	0.091 m/s Standard Error 0.0326	0.084 m/s Standard Error 0.0329
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	0.041 m/s Standard Error 0.0295
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	0.150 m/s Standard Error 0.0417
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	0.075 m/s Standard Error 0.0407

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Modified Intent-to-Treat/Evaluables (All subjects with nonmissing Baseline and primary endpoint data)

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.

Outcome measures

Measure	AKST4290 n=45 Participants Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=45 Participants Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral 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	1.7 hours Standard Error 1.24	0.4 hours Standard Error 1.24
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	-1.3 hours Standard Error 1.06

Adverse Events

AKST4290

Serious events: 1 serious events

Other events: 8 other events

Deaths: 1 deaths

Placebo

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	AKST4290 n=52 participants at risk Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=55 participants at risk Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
General disorders Sudden cardiac death	1.9% 1/52 • Baseline to Week 14	0.00% 0/55 • Baseline to Week 14
Infections and infestations Clostridium difficile colitis	0.00% 0/52 • Baseline to Week 14	1.8% 1/55 • Baseline to Week 14
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/52 • Baseline to Week 14	1.8% 1/55 • Baseline to Week 14
Psychiatric disorders Neuropsychiatric syndrome	0.00% 0/52 • Baseline to Week 14	1.8% 1/55 • Baseline to Week 14

Other adverse events

Measure	AKST4290 n=52 participants at risk Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks. AKST4290: Oral AKST4290	Placebo n=55 participants at risk Subjects will receive placebo, twice daily, for 12 weeks. Placebo: Oral Placebo
Gastrointestinal disorders Nausea	5.8% 3/52 • Baseline to Week 14	0.00% 0/55 • Baseline to Week 14
General disorders Fatigue	5.8% 3/52 • Baseline to Week 14	0.00% 0/55 • Baseline to Week 14
Injury, poisoning and procedural complications Fall	0.00% 0/52 • Baseline to Week 14	5.5% 3/55 • Baseline to Week 14
Investigations Electrocardiogram QT prolonged	1.9% 1/52 • Baseline to Week 14	7.3% 4/55 • Baseline to Week 14
Musculoskeletal and connective tissue disorders Back pain	1.9% 1/52 • Baseline to Week 14	7.3% 4/55 • Baseline to Week 14

Additional Information

Clinical Development

Alkahest, Inc.

Phone: (650) 801-0474

Email: trials@alkahest.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution and its employees and agents, and Principal Investigator shall not disclose to any third party or use for any purpose other than in the fulfillment of their respective obligations hereunder, any data, records or other information disclosed to Institution and Principal Investigator by Sponsor or Clinical Research Organization, or generated as a result of this Study, without the prior written consent of Sponsor (or PPD as the case may be) (hereinafter, collectively "Information").
• Publication restrictions are in place

Restriction type: OTHER