Study Assessing Efficacy and Safety of AKST4290 in Subjects With Parkinson's Disease on Stable Dopaminergic Treatment (TEAL)
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|ClinicalTrials.gov Identifier: NCT04369430|
Recruitment Status : Completed
First Posted : April 30, 2020
Results First Posted : October 10, 2022
Last Update Posted : October 10, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Drug: AKST4290 Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AKST4290 in Subjects With Parkinson's Disease on Stable Dopaminergic Treatment|
|Actual Study Start Date :||January 16, 2020|
|Actual Primary Completion Date :||February 11, 2021|
|Actual Study Completion Date :||March 10, 2021|
Subjects will receive AKST4290, 400 mg twice daily, for 12 weeks.
Placebo Comparator: Placebo
Subjects will receive placebo, twice daily, for 12 weeks.
- Change in Motor Function During Levodopa Withdrawal. [ Time Frame: 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.
- Safety as Assessed by the Incidence, Seriousness and Severity of Adverse Events (AEs). [ Time Frame: 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.
- Evaluation of Laboratory Changes. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.
- The Schwab and England Activities of Daily Living (SE-ADL) Scale, Change From Baseline in SE-ADL During the On-medication State. [ Time Frame: 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.
- The Clinical Impression of Severity Index - PD (CISI-PD), Change From Baseline in CISI-PD During the On-medication State. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
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|Ages Eligible for Study:||50 Years to 80 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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/Exclusion criteria may apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369430
|Study Director:||Alkahest Medical Monitor||Alkahest, Inc.|
Documents provided by Alkahest, Inc.:
|Responsible Party:||Alkahest, Inc.|
|Other Study ID Numbers:||
|First Posted:||April 30, 2020 Key Record Dates|
|Results First Posted:||October 10, 2022|
|Last Update Posted:||October 10, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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