Cognitive Dysfunction, Parkinson Disease
Conditions
Keywords
Parkinson's Disease, Cognitive Dysfunction, SAGE-718
Brief summary
The primary purpose of this two-part study was to evaluate the safety and tolerability of SAGE-718 and its effects on cognitive, neuropsychiatric, and motor symptoms in participants with Parkinson's disease mild cognitive impairment (PD-MCI).
Interventions
DRUGSAGE-718
Oral tablets.
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study had two parts: Part A and Part B with unique participants for each study part. Part B was started after Part A was completed.
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Meet the following criteria for PD-MCI: Have a confirmed diagnosis of idiopathic PD according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria; Meet MDS Task Force Criteria for MCI in PD. 2. Have a score of 20 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at Screening. 3. Meet criteria for Hoehn & Yahr Stage I to III (mild to moderate motor severity) at Screening. 4. Have stable motor symptoms for at least 4 weeks prior to screening, in the opinion of the investigator.
Exclusion criteria
1. Have a diagnosis of dementia of any etiology, including but not limited to: Dementia associated with PD (probable or possible), Dementia with Lewy Bodies, Alzheimer's Dementia, and Vascular Dementia. 2. Have any indication of parkinsonism other than idiopathic PD. 3. In the opinion of the investigator, be experiencing unpredictable fluctuations in motor and/or nonmotor symptoms associated with PD. 4. Have an ongoing central nervous system condition other than idiopathic PD, including active neurologic and/or nonremitted psychiatric disorders, in the opinion of the investigator. 5. Have a history of brain surgery, deep brain stimulation, a significant head injury causing loss of consciousness greater than 30 minutes, or hospitalization due to a brain injury. 6. Have experienced significant psychotic symptoms within the past 3 months, including those associated with PD medications, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | From first dose of study drug up to 28 days | An adverse event (AE) was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal. |
| Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | From first dose of study drug up to 42 days | An AE was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements | From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B | Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported. |
| Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments | From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B | Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported. |
| Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements | From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B | Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia \[QTcF\]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported. |
| Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B | The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included yes or no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled in the study at 4 investigative sites in the United States and took part in the study that ran from 31 July 2020 to 25 March 2022.
Participants by arm
| Arm | Count |
|---|---|
| Part A: SAGE-718 3 mg Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study. | 11 |
| Part B: SAGE-718 3 mg Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study. | 7 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A (28 Days) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Part B: SAGE-718 3 mg | Total | Part A: SAGE-718 3 mg |
|---|---|---|---|
| Age, Continuous | 70.3 years | 69.6 years | 69.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 18 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 18 Participants | 11 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 14 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 7 |
| other Total, other adverse events | 5 / 11 | 1 / 7 |
| serious Total, serious adverse events | 0 / 11 | 0 / 7 |
Outcome results
Primary
Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
An adverse event (AE) was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
Time frame: From first dose of study drug up to 28 days
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SAGE-718 3 mg | Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 45.5 percentage of participants |
Primary
Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
An AE was any untoward medical occurrence in a participant administered with a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
Time frame: From first dose of study drug up to 42 days
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SAGE-718 3 mg | Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 14.3 percentage of participants |
Secondary
Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included yes or no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.
Time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: SAGE-718 3 mg | Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 percentage of participants |
| Part A: SAGE-718 3 mg | Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 percentage of participants |
| Part B: SAGE-718 3 mg | Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 percentage of participants |
| Part B: SAGE-718 3 mg | Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 percentage of participants |
Secondary
Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements
Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia \[QTcF\]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements | 0 percentage of participants |
| Part B: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements | 0 percentage of participants |
Secondary
Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments
Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments | 0 percentage of participants |
| Part B: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments | 0 percentage of participants |
Secondary
Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements
Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.
Time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
Population: Safety Set included all participants who were administered IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 percentage of participants |
| Part B: SAGE-718 3 mg | Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements | 0 percentage of participants |