Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded By Severity, Serious TEAEs and Trial Discontinuation Due to TEAEs |
An AE is any untoward medical occurrence in a clinical trial participant administered a medicinal product that does not necessarily have a causal relationship with the treatment. An SAE: AE that results in the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions i.e. fatal, life-threatening, result in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, and requires inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE that started after trial drug treatment; or if the event was continuous from baseline and was worsening, serious, trial drug-related, or resulted in death, discontinuation, interruption, or reduction of trial therapy. TEAEs were graded as, Mild: Discomfort noticed, but no disruption to daily activity, Moderate: Discomfort sufficient to reduce or affect normal daily activity, and Severe: Inability to work or perform normal daily activity. |
From the first dose of study drug (in current study) up to 21 days after the last dose of study drug (up to approximately 29 weeks) |
|
| Primary |
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs |
Vital signs measurements included body weight, body temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and standing positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per protocol-predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for vital signs are reported. |
Baseline (current study) up to Week 26 |
|
| Primary |
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities |
Twelve-lead ECG recordings were obtained after the participant was supine and at rest for at least 5 minutes. Criteria for identifying ECG measurements of potential clinical relevance included Rate: Tachycardia (Vent =110 beats per minute [bpm]; increase =15bpm), Bradycardia (Vent = 60bpm; decrease =15bpm); Rhythm: Sinus tachycardia (= 110bpm; an increase of =15 bpm), Sinus bradycardia (= 60bpm; a decrease of =15 bpm), Supraventricular premature beat (not present at baseline and present post-baseline), Conduction: Right bundle branch block (not present at baseline and present post-baseline) and ST/T Morphology: Symmetrical T-Wave Inversion (not present at baseline and present post-baseline). The categories with at least one participant with clinically relevant ECG abnormalities are reported. |
Baseline (current study) up to Week 26 |
|
| Primary |
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities |
Laboratory assessments included - serum chemistry including prolactin and thyrotropin, hematology, and urinalysis. Number of participants with potentially clinically relevant laboratory test abnormalities were reported as per criteria defined in SAP. The categories with at least one participant with clinically relevant value outside the normal range for laboratory assessments are reported. |
Baseline (current study) up to Week 26 |
|
| Primary |
Number of Participants With Potentially Clinically Relevant Abnormal Physical Examination Values |
Physical examination included measurement of height and the examination of the head, ears, eyes, nose, and throat (HEENT); thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae. Participants with abnormal values, as assessed by the investigator were reported. |
Baseline (current study) up to Week 26 |
|
| Primary |
Number of Participants With Suicidality as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS) |
Suicidality as defined as at least one occurrence of suicidal ideation or suicidal behavior, was assessed using C-SSRS. The assessment included "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) & suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for suicidal ideation: Score range of 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent), higher total scores indicate more suicidal ideation; Suicidal behavior: Score range of 0 (no suicidal behavior) to 4 (actual suicide attempt), higher total scores indicate more suicidal behavior. Number of participants with at least one occurrence of suicidal ideation or suicidal behavior was reported. |
Baseline (current study) up to Week 26 |
|
| Primary |
Change From Baseline in Simpson Angus Scale (SAS) Total Score at Week 2 |
SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms. |
Baseline and Week 2 |
|
| Primary |
Change From Baseline in SAS Total Score at Week 14 |
SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms. |
Baseline and Week 14 |
|
| Primary |
Change From Baseline in SAS Total Score at Week 26 |
SAS was used to evaluate extrapyramidal symptoms (EPS). The SAS consists of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Severity of each item was rated on a 5-point Likert scale, with a score of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores of all 10 items, ranging from 0 to 40 where a higher score indicates a severe condition. Negative change from baseline indicates absence of symptoms. |
Baseline and Week 26 |
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| Primary |
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Week 2 |
The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition. |
Baseline and Week 2 |
|
| Primary |
Change From Baseline in AIMS Total Score at Week 14 |
The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition. |
Baseline and Week 14 |
|
| Primary |
Change From Baseline in AIMS Total Score at Week 26 |
The AIMS is a 12-item scale. The first 10 items are rated on a Likert 5-point scale from 0 to 4 (0 = best, 4 = worst). An item score of 0, depending on specific item, means either "no abnormal Involuntary movement (AIM)" or "no incapacitation due to AIM" or "no awareness of AIM". An item score of 4 means either "severe AIM" or "severe incapacitation due to AIM" or "being aware of, and severe distress caused by AIM". Items 11 and 12 are related to dental status, taking dichotomous response: 0 = no and 1 = yes. AIMS movement score is the sum of the ratings for the first seven items with possible total scores of 0 to 28, where a higher score indicates a severe condition. A negative change from baseline indicates less symptoms. |
Baseline and Week 26 |
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| Primary |
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score at Week 2 |
The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms. |
Baseline and Week 2 |
|
| Primary |
Change From Baseline in BARS Score at Week 14 |
The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms and negative change from baseline indicate less symptoms. |
Baseline and Week 14 |
|
| Primary |
Change From Baseline in BARS Score at Week 26 |
The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items were rated on a 4-point Likert scale, with a score of 0 (absence of symptoms) to 3 (severe condition) and the global clinical assessment was rated on a 6-point scale, with a score of 0 (absence of symptoms) to 5 (severe akathisia). Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Lower scores indicate less symptoms and negative change from baseline indicate less symptoms. |
Baseline and Week 26 |
|
| Primary |
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 14 |
Percentage of participants who had significant weight gain (= 7% increase in body weight relative to baseline) and significant weight loss (= 7% decrease in body weight relative to baseline) were reported. |
Baseline up to Week 14 |
|
| Primary |
Percentage of Participants With Potentially Clinically Relevant Changes in Weight up to Week 26 |
Percentage of participants who had significant weight gain (= 7% increase in body weight relative to baseline) and significant weight loss (= 7% decrease in body weight relative to baseline) were reported. |
Baseline up to Week 26 |
|
| Primary |
Time to Discontinuation Due to AE |
The time to discontinuation due to AE was defined as the total number of days between the enrolment date and the discontinuation date. The time to discontinuation was analyzed using the Kaplan Meier curve. |
Baseline (in current study) up to 21 days post last dose of study drug (up to approximately 29 weeks) |
|
| Secondary |
Mean Change From Baseline to Week 26 in Aberrant Behavior Checklist - Irritability (ABC-I) Subscale Score |
The ABC is parent-reported rating scale designed to assess treatment effects on problem behavior in participants with intellectual disabilities. The ABC scale has 58 items, which divide into 5 subscales as follows:(1) Irritability, Agitation; (2) Lethargy, Social Withdrawal; (3) Stereotypic Behavior; (4) Hyperactivity, Noncompliance; and (5) Inappropriate Speech. Each of the 58 ABC items is rated on a 4-point scale (0 = not at all a problem; 1=the behavior is a problem, but slight in degree; 2=problem is moderately serious; 3=problem is severe in degree). The Irritability subscale (ABC-I) measures emotional and behavioral symptoms of ASD, including aggression toward others, deliberate self-injuriousness, temper tantrums, & quickly changing moods. ABC-I total score is the sum of the ratings over 15 ABC items. Individual scores were summed, thus the ABC-I total score ranges from 0 to 45. Higher scores represent the worst condition. Negative change from baseline indicates less symptoms. |
Baseline (current study), Week 26 |
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| Secondary |
Mean Change From Baseline to Week 26 in Clinical Global Impression - Severity (CGI-S) Scale Score |
The CGI-S scale is a clinician-rated assessment that evaluates the severity of a participant's condition with a focus on symptoms of irritability on a 7-point scale. The investigator (or rater) answered the following question: "Considering your total clinical experience with this particular population, how ill was the participant at this time with regard to symptoms of irritability?" Response choices were 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. The total score ranges from 0 to 7, where higher scores indicate worse condition. A negative change from baseline indicates less symptoms. |
Baseline (current study), Week 26 |
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