Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, SHP465, Hyperactivity
Brief summary
The purpose of the study is to evaluate the long-term safety and tolerability of SHP465 at 6.25 milligram (mg) in children aged 4 to 12 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD).
Interventions
DRUGSHP465
SHP465 capsule will be administered in a dose of 6.25 mg orally once daily for 360 days.
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Participant is male or female aged 4-12 years inclusive at the time of consent. * Participant's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (as applicable) by the participant. * Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (any subtype). * Participant who is a female and of child-bearing potential must not be pregnant and agree to comply with any applicable contraceptive requirements.. * Participant has an ADHD-RS-5 Child, Home Version Total Score of greater than or equal to (\>=) 28 and Clinical Global Impression - Severity of Illness (CGI-S) score \>=4 at baseline (Visit 2). Participant is currently not on ADHD therapy, or is not completely satisfied with their current ADHD therapy.
Exclusion criteria
* Participant is required or anticipated to take medications that have central nervous system effects or affect performance. Stable use of bronchodilator inhalers is not exclusionary. * Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the participant. - Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product. * Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy. * Participant has a known family history of sudden cardiac death or ventricular arrhythmia. * Participant has a blood pressure measurement \>=95th percentile for age, sex, and height at screening (Visit 1) and/or baseline (Visit 2). * Participant has a height less than or equal to (\<=) 5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2). * Participant has a weight \<=5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2). * Participant has a known history of symptomatic cardiovascular disease, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac conditions placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug. * Participant has a history of seizures (other than infantile febrile seizures). * Participant is taking any medication that is excluded per the protocol. * Participant had any clinically significant ECG or clinical laboratory abnormalities at the screening (Visit 1) or baseline visit (Visit 2). * Participant has current abnormal thyroid function, defined as abnormal thyroid-stimulating hormone and thyroxine at the screening or baseline visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted. * Participant is currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or currently demonstrating suicidal ideation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 | Day 330 | C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The number of participants with postive response in suicidal ideation and suicidal behavior were reported. |
| Length of Time Sleeping Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA (up to 330 days) | PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time sleeping per night was assessed at FoTA. |
| Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment (FoTA) | FoTA (up to 330 days) | CSHQ was a tool designed to screen for the most common sleep problems in children and consisted of 33 items for scoring and several extra items intended to provide administrators with other potentially useful information about respondents. The instrument evaluates the 8 different subscales: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. A 3-point scale was used for rating: usually if the sleep behavior occurs 5 to 7 times per week, sometimes for 2 to 4 times per week, and rarely for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From start of study drug administration up to follow-up (approximately up to 367 days) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of investigational product. |
| Change From Baseline in Pulse Rate at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Change from baseline in pulse rate at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study. |
| Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study. |
| Change From Baseline in Height at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Height was measured in centimeters (cm) without shoes and with light clothing using a stadiometer. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study. |
| Change From Baseline in Weight at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Weight was measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study. |
| Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils band form, segmented neutrophils, neutrophils/total cells and platelets were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Leukocytes at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology leukocytes parameter: basophils, eosinophils, lymphocytes, monocytes and neutrophil were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Erythrocytes at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter erythrocytes were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin Concentration at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin concentration were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Hematocrit at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter hematocrit were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Hemoglobin at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 | Baseline, Early termination/Day 360 | Change from baseline in hematology parameter erythrocytes mean corpuscular volume and mean platelet volume were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in chemistry parameter alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, and lactate dehydrogenase were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in chemistry parameters albumin and protein were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in chemistry parameters blood urea nitrogen, cholesterol, glucose, phosphate, potassium, sodium and urate were studies. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in chemistry parameters bilirubin and creatinine were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Thyrotropin at Early Termination/ Day 360 | Baseline, Early termination/Day 360 | Change from baseline in thyrotropin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Thyroxine,Free at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in thyroxine,free were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Urinalysis (Specific Gravity) at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in urine specific gravity were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Urobilinogen at Early Termination/Day 360 | Baseline, Early termination/Day 360 | Change from baseline in urobilinogen were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Urine Potential of Hydrogen (pH) at Early Termination/Day 360 | Baseline, Early Termination/Day 360 | Change from baseline in urine pH were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Change From Baseline in Heart Rate at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Heart rate was measured by Electrocardiogram (ECG). ECG was performed using the central ECG provider's equipment and was send to the central ECG provider electronically. Change from baseline in heart rate at FoTA were reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product. |
| Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | ECG was performed using the central ECG provider's equipment and was sent to the central ECG provider electronically to measure PR, RR, QRS , QT, QTcB and QTcF intervals. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date).Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product. |
| Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA (up to 330 days) | PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. The assessment was done by the nature of the responses, not by a numbered scale. Participants analyzed for number of times woke up per night category were only the participants who responded as yes for the woke up during the night category in this outcome measure. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. |
| Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA (up to 330 days) | PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time awake per night and length of time to fall asleep per night was assessed at FoTA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement (CGI-I) at Final On-Treatment Assessment (FoTA) | FoTA (up to 330 days) | CGI-I scale was performed to rate the improvement of a participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). |
| Change From Baseline in Clinician-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Final On-Treatment Assessment (FoTA) | Baseline, FoTA (up to 330 days) | Clinician administered ADHD-RS-5, child, home version total score were analyzed. ADHD-RS-5 consists of 18 items designed to reflect current symptomatology of ADHD based on diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items may be grouped into 2 subscales: hyperactivity/impulsivity (9 items) and inattentiveness (9 items). Higher total scores indicated higher impairment and lower scores indicated no impairment. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 33 centers in the United States between 02 January 2018 (first participant first visit) and 19 January 2019 (last participant last visit).
Pre-assignment details
Overall, 141 participants enrolled and received the treatment in two groups (Group A and B). Participants who completed antecedent studies SHP465-112 (NCT03327402) or SHP465-309 (NCT03325881) were in Group A and participants who were directly enrolled into this study were in Group B.
Participants by arm
| Arm | Count |
|---|---|
| Group A (Antecedent Studies) Participants who completed antecedent studies SHP465-112 (NCT03327402) or SHP465-309 (NCT03325881) were in group A and received 6.25 milligram (mg) SHP465 capsule orally once daily for up to 330 days. | 63 |
| Group B (Direct Enrollment) Participants who directly enrolled in this study were in group B and received 6.25 mg SHP465 capsule orally once daily for up to 330 days. | 77 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 8 | 14 |
| Overall Study | Lost to Follow-up | 4 | 9 |
| Overall Study | Other (Not received Treatment) | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Study Terminated by Sponsor | 38 | 43 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Group B (Direct Enrollment) | Total | Group A (Antecedent Studies) |
|---|---|---|---|
| Age, Continuous | 6.1 years STANDARD_DEVIATION 2.33 | 6.8 years STANDARD_DEVIATION 2.56 | 7.5 years STANDARD_DEVIATION 2.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 42 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 97 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 36 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 8 Participants | 6 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 | 57 Participants | 94 Participants | 37 Participants |
| Sex: Female, Male Female | 28 Participants | 50 Participants | 22 Participants |
| Sex: Female, Male Male | 49 Participants | 90 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 77 |
| other Total, other adverse events | 12 / 63 | 20 / 77 |
| serious Total, serious adverse events | 0 / 63 | 1 / 77 |
Outcome results
Primary
Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA)
Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) | SBP: Change at FoTA | 0.6 Millimeters of mercury | Standard Deviation 7.17 |
| Group A (Antecedent Studies) | Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) | DBP: Change at FoTA | 2.3 Millimeters of mercury | Standard Deviation 7.76 |
| Group B (Direct Enrollment) | Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) | SBP: Change at FoTA | 0.6 Millimeters of mercury | Standard Deviation 7.36 |
| Group B (Direct Enrollment) | Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) | DBP: Change at FoTA | 1.7 Millimeters of mercury | Standard Deviation 6.03 |
Primary
Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360
Change from baseline in chemistry parameters albumin and protein were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 | Albumin | -0.2 gram per liter | Standard Deviation 2.82 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 | Protein | 0.7 gram per liter | Standard Deviation 4.27 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 | Albumin | -0.1 gram per liter | Standard Deviation 2.45 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 | Protein | 1.0 gram per liter | Standard Deviation 3.55 |
Primary
Change From Baseline in Chemistry Parameters at Early Termination/Day 360
Change from baseline in chemistry parameter alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, and lactate dehydrogenase were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Alkaline Phosphatase | -18.2 Unit per liter | Standard Deviation 62.28 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Gamma Glutamyl Transferase | -0.4 Unit per liter | Standard Deviation 2.2 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Aspartate Aminotransferase | -1.9 Unit per liter | Standard Deviation 5.27 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Lactate Dehydrogenase | -9.0 Unit per liter | Standard Deviation 24.24 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Alanine Aminotransferase | -2.3 Unit per liter | Standard Deviation 4.18 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Lactate Dehydrogenase | 26.2 Unit per liter | Standard Deviation 185.52 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Alanine Aminotransferase | 9.6 Unit per liter | Standard Deviation 52.75 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Alkaline Phosphatase | -32.6 Unit per liter | Standard Deviation 68.15 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Aspartate Aminotransferase | 21.4 Unit per liter | Standard Deviation 129.48 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters at Early Termination/Day 360 | Gamma Glutamyl Transferase | 1.3 Unit per liter | Standard Deviation 5.06 |
Primary
Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360
Change from baseline in chemistry parameters bilirubin and creatinine were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 | Creatinine | 3.3 micromoles per liter | Standard Deviation 8.2 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 | Bilirubin | 0.90 micromoles per liter | Standard Deviation 3.644 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 | Bilirubin | -0.14 micromoles per liter | Standard Deviation 2.994 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 | Creatinine | 6.7 micromoles per liter | Standard Deviation 17.15 |
Primary
Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360
Change from baseline in chemistry parameters blood urea nitrogen, cholesterol, glucose, phosphate, potassium, sodium and urate were studies. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Blood Urea Nitrogen | -0.235 millimoles per liter | Standard Deviation 1.0664 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Calcium | 0.035 millimoles per liter | Standard Deviation 0.1101 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Cholesterol | -0.082 millimoles per liter | Standard Deviation 0.4592 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Glucose | -0.183 millimoles per liter | Standard Deviation 0.9841 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Phosphate | -0.045 millimoles per liter | Standard Deviation 0.194 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Potassium | -0.02 millimoles per liter | Standard Deviation 0.569 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Sodium | 0.8 millimoles per liter | Standard Deviation 2.57 |
| Group A (Antecedent Studies) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Urate | -0.0073 millimoles per liter | Standard Deviation 0.04488 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Urate | 0.0142 millimoles per liter | Standard Deviation 0.0718 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Blood Urea Nitrogen | -0.036 millimoles per liter | Standard Deviation 1.4248 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Phosphate | -0.153 millimoles per liter | Standard Deviation 0.2056 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Calcium | 0.004 millimoles per liter | Standard Deviation 0.0977 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Sodium | 0.3 millimoles per liter | Standard Deviation 2.48 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Cholesterol | -0.295 millimoles per liter | Standard Deviation 0.8294 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Potassium | -0.01 millimoles per liter | Standard Deviation 0.367 |
| Group B (Direct Enrollment) | Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 | Glucose | 0.138 millimoles per liter | Standard Deviation 0.9205 |
Primary
Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA)
ECG was performed using the central ECG provider's equipment and was sent to the central ECG provider electronically to measure PR, RR, QRS , QT, QTcB and QTcF intervals. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date).Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: PR Interval | -1.77 milliseconds | Standard Deviation 10.129 |
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: RR Interval | -18.05 milliseconds | Standard Deviation 71.382 |
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QRS Interval | 0.93 milliseconds | Standard Deviation 4.419 |
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QT Interval | -4.74 milliseconds | Standard Deviation 17.826 |
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QTcB Interval | -0.52 milliseconds | Standard Deviation 14.145 |
| Group A (Antecedent Studies) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QTcF Interval | -1.97 milliseconds | Standard Deviation 13.126 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QTcB Interval | -1.39 milliseconds | Standard Deviation 14.796 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: PR Interval | 0.14 milliseconds | Standard Deviation 8.539 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QT Interval | -1.49 milliseconds | Standard Deviation 18.616 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: RR Interval | -1.77 milliseconds | Standard Deviation 88.658 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QTcF Interval | -1.37 milliseconds | Standard Deviation 11.808 |
| Group B (Direct Enrollment) | Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) | FoTA: QRS Interval | 1.62 milliseconds | Standard Deviation 5.688 |
Primary
Change From Baseline in Erythrocytes at Early Termination/Day 360
Change from baseline in hematology parameter erythrocytes were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Erythrocytes at Early Termination/Day 360 | 0.017 10^12 cells per liter | Standard Deviation 0.3368 |
| Group B (Direct Enrollment) | Change From Baseline in Erythrocytes at Early Termination/Day 360 | -0.007 10^12 cells per liter | Standard Deviation 0.2889 |
Primary
Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin at Early Termination/Day 360
Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin at Early Termination/Day 360 | 0.42 picogram | Standard Deviation 0.642 |
| Group B (Direct Enrollment) | Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin at Early Termination/Day 360 | 0.38 picogram | Standard Deviation 1.259 |
Primary
Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin Concentration at Early Termination/Day 360
Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin concentration were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin Concentration at Early Termination/Day 360 | -0.09 gram per deciliter | Standard Deviation 0.664 |
| Group B (Direct Enrollment) | Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin Concentration at Early Termination/Day 360 | -0.16 gram per deciliter | Standard Deviation 1.018 |
Primary
Change From Baseline in Heart Rate at Final On-Treatment Assessment (FoTA)
Heart rate was measured by Electrocardiogram (ECG). ECG was performed using the central ECG provider's equipment and was send to the central ECG provider electronically. Change from baseline in heart rate at FoTA were reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Heart Rate at Final On-Treatment Assessment (FoTA) | 1.78 beats per minute | Standard Deviation 7.618 |
| Group B (Direct Enrollment) | Change From Baseline in Heart Rate at Final On-Treatment Assessment (FoTA) | -0.12 beats per minute | Standard Deviation 10.973 |
Primary
Change From Baseline in Height at Final On-Treatment Assessment (FoTA)
Height was measured in centimeters (cm) without shoes and with light clothing using a stadiometer. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Height at Final On-Treatment Assessment (FoTA) | 3.7 centimeter | Standard Deviation 4.6 |
| Group B (Direct Enrollment) | Change From Baseline in Height at Final On-Treatment Assessment (FoTA) | 2.9 centimeter | Standard Deviation 2.49 |
Primary
Change From Baseline in Hematocrit at Early Termination/Day 360
Change from baseline in hematology parameter hematocrit were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Hematocrit at Early Termination/Day 360 | 0.86 percentage of hematocrit | Standard Deviation 2.784 |
| Group B (Direct Enrollment) | Change From Baseline in Hematocrit at Early Termination/Day 360 | 0.59 percentage of hematocrit | Standard Deviation 2.901 |
Primary
Change From Baseline in Hematology Parameters at Early Termination/Day 360
Change from baseline in hematology parameter basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils band form, segmented neutrophils, neutrophils/total cells and platelets were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Eosinophils | 0.02 10^9 cells per liter | Standard Deviation 0.389 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Neutrophils Band Form | 0.00 10^9 cells per liter | Standard Deviation 0 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Lymphocytes | 0.14 10^9 cells per liter | Standard Deviation 0.948 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Segmented Neutrophils | -0.40 10^9 cells per liter | Standard Deviation 1.296 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Leukocytes | -0.25 10^9 cells per liter | Standard Deviation 1.519 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Neutrophils/Total Cells | -0.32 10^9 cells per liter | Standard Deviation 1.349 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Monocytes | -0.12 10^9 cells per liter | Standard Deviation 0.282 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Platelets | 8.0 10^9 cells per liter | Standard Deviation 46.76 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Basophils | -0.01 10^9 cells per liter | Standard Deviation 0.04 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Platelets | 4.6 10^9 cells per liter | Standard Deviation 60.19 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Basophils | 0.01 10^9 cells per liter | Standard Deviation 0.051 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Eosinophils | 0.04 10^9 cells per liter | Standard Deviation 0.24 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Leukocytes | -0.09 10^9 cells per liter | Standard Deviation 2.107 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Lymphocytes | -0.12 10^9 cells per liter | Standard Deviation 0.685 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Monocytes | 0.01 10^9 cells per liter | Standard Deviation 0.217 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Neutrophils Band Form | 0.00 10^9 cells per liter | Standard Deviation 0.049 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Segmented Neutrophils | -0.02 10^9 cells per liter | Standard Deviation 2.139 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters at Early Termination/Day 360 | Neutrophils/Total Cells | 0.00 10^9 cells per liter | Standard Deviation 1.915 |
Primary
Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360
Change from baseline in hematology parameter erythrocytes mean corpuscular volume and mean platelet volume were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 | Erythrocytes Mean Corpuscular Volume | 1.48 femtoliters | Standard Deviation 1.438 |
| Group A (Antecedent Studies) | Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 | Mean Platelet Volume | -0.1 femtoliters | Standard Deviation 0.77 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 | Erythrocytes Mean Corpuscular Volume | 1.46 femtoliters | Standard Deviation 2.565 |
| Group B (Direct Enrollment) | Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 | Mean Platelet Volume | 0.2 femtoliters | Standard Deviation 0.96 |
Primary
Change From Baseline in Hemoglobin at Early Termination/Day 360
Change from baseline in hematology parameter hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Hemoglobin at Early Termination/Day 360 | 2.5 gram per liter | Standard Deviation 8.68 |
| Group B (Direct Enrollment) | Change From Baseline in Hemoglobin at Early Termination/Day 360 | 1.5 gram per liter | Standard Deviation 9.82 |
Primary
Change From Baseline in Leukocytes at Early Termination/Day 360
Change from baseline in hematology leukocytes parameter: basophils, eosinophils, lymphocytes, monocytes and neutrophil were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Lymphocytes/Leukocytes | 4.42 percentage of leukocytes | Standard Deviation 12.14 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils Band Form/Leukocytes | 0.0 percentage of leukocytes | Standard Deviation 0 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Eosinophils/Leukocytes | 0.38 percentage of leukocytes | Standard Deviation 4.288 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils, Segmented/Leukocytes | -3.8 percentage of leukocytes | Standard Deviation 12.39 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Monocytes/Leukocytes | -1.02 percentage of leukocytes | Standard Deviation 3.982 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils/Leukocytes | -3.62 percentage of leukocytes | Standard Deviation 13.359 |
| Group A (Antecedent Studies) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Basophils/Leukocytes | -0.17 percentage of leukocytes | Standard Deviation 0.631 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils/Leukocytes | 0.35 percentage of leukocytes | Standard Deviation 11.756 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Basophils/Leukocytes | 0.04 percentage of leukocytes | Standard Deviation 0.589 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Eosinophils/Leukocytes | 0.30 percentage of leukocytes | Standard Deviation 3.222 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Lymphocytes/Leukocytes | -0.97 percentage of leukocytes | Standard Deviation 11.517 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Monocytes/Leukocytes | 0.52 percentage of leukocytes | Standard Deviation 2.65 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils Band Form/Leukocytes | 0.0 percentage of leukocytes | Standard Deviation 0.62 |
| Group B (Direct Enrollment) | Change From Baseline in Leukocytes at Early Termination/Day 360 | Neutrophils, Segmented/Leukocytes | -0.6 percentage of leukocytes | Standard Deviation 13.15 |
Primary
Change From Baseline in Pulse Rate at Final On-Treatment Assessment (FoTA)
Change from baseline in pulse rate at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Pulse Rate at Final On-Treatment Assessment (FoTA) | 1.5 beats per minute | Standard Deviation 9.82 |
| Group B (Direct Enrollment) | Change From Baseline in Pulse Rate at Final On-Treatment Assessment (FoTA) | 0.1 beats per minute | Standard Deviation 10.31 |
Primary
Change From Baseline in Thyrotropin at Early Termination/ Day 360
Change from baseline in thyrotropin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Thyrotropin at Early Termination/ Day 360 | 0.2576 milli-international units per litre | Standard Deviation 0.98862 |
| Group B (Direct Enrollment) | Change From Baseline in Thyrotropin at Early Termination/ Day 360 | 0.2392 milli-international units per litre | Standard Deviation 0.90169 |
Primary
Change From Baseline in Thyroxine,Free at Early Termination/Day 360
Change from baseline in thyroxine,free were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Thyroxine,Free at Early Termination/Day 360 | 0.61 picomole per liter | Standard Deviation 1.851 |
| Group B (Direct Enrollment) | Change From Baseline in Thyroxine,Free at Early Termination/Day 360 | -0.46 picomole per liter | Standard Deviation 2.632 |
Primary
Change From Baseline in Urinalysis (Specific Gravity) at Early Termination/Day 360
Change from baseline in urine specific gravity were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Urinalysis (Specific Gravity) at Early Termination/Day 360 | 0.0029 Ratio | Standard Deviation 0.00762 |
| Group B (Direct Enrollment) | Change From Baseline in Urinalysis (Specific Gravity) at Early Termination/Day 360 | 0.0010 Ratio | Standard Deviation 0.00923 |
Primary
Change From Baseline in Urine Potential of Hydrogen (pH) at Early Termination/Day 360
Change from baseline in urine pH were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early Termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Urine Potential of Hydrogen (pH) at Early Termination/Day 360 | 0.1 pH | Standard Deviation 0.83 |
| Group B (Direct Enrollment) | Change From Baseline in Urine Potential of Hydrogen (pH) at Early Termination/Day 360 | 0.1 pH | Standard Deviation 1.07 |
Primary
Change From Baseline in Urobilinogen at Early Termination/Day 360
Change from baseline in urobilinogen were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: Baseline, Early termination/Day 360
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Urobilinogen at Early Termination/Day 360 | 0.09 milligrams per deciliter | Standard Deviation 0.393 |
| Group B (Direct Enrollment) | Change From Baseline in Urobilinogen at Early Termination/Day 360 | 0.05 milligrams per deciliter | Standard Deviation 0.309 |
Primary
Change From Baseline in Weight at Final On-Treatment Assessment (FoTA)
Weight was measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Time frame: Baseline, FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Weight at Final On-Treatment Assessment (FoTA) | 1.4 kilograms | Standard Deviation 2.93 |
| Group B (Direct Enrollment) | Change From Baseline in Weight at Final On-Treatment Assessment (FoTA) | 1.1 kilograms | Standard Deviation 2.41 |
Primary
Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA)
PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time awake per night and length of time to fall asleep per night was assessed at FoTA.
Time frame: FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Antecedent Studies) | Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | Length of Time to Fall Asleep per Night | 20.2 minutes | Standard Deviation 17.12 |
| Group A (Antecedent Studies) | Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | Length of Time Awake per Night | 8.8 minutes | Standard Deviation 4.14 |
| Group B (Direct Enrollment) | Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | Length of Time to Fall Asleep per Night | 22.3 minutes | Standard Deviation 24.74 |
| Group B (Direct Enrollment) | Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | Length of Time Awake per Night | 14.4 minutes | Standard Deviation 23.1 |
Primary
Length of Time Sleeping Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA)
PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time sleeping per night was assessed at FoTA.
Time frame: FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Length of Time Sleeping Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | 9.1 hours | Standard Deviation 1.4 |
| Group B (Direct Enrollment) | Length of Time Sleeping Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | 9.6 hours | Standard Deviation 1.21 |
Primary
Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330
C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The number of participants with postive response in suicidal ideation and suicidal behavior were reported.
Time frame: Day 330
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Antecedent Studies) | Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 | Suicidal Ideation | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 | Suicidal Behavior | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 | Suicidal Ideation | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 | Suicidal Behavior | 0 Participants |
Primary
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA)
PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. The assessment was done by the nature of the responses, not by a numbered scale. Participants analyzed for number of times woke up per night category were only the participants who responded as yes for the woke up during the night category in this outcome measure. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Time frame: FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Woke up during the night - Yes | 17 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Woke up during the night - No | 46 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 0 | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 1 | 12 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 2 | 4 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 3 | 1 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 4 | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night >= 5 | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Very Poor | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Poor | 6 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Average | 23 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Good | 24 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Very Good | 10 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week a typical week - Yes | 48 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week a typical week - No | 15 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - Vacation | 4 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - School break | 7 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - Friend house | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - ill | 0 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - other | 4 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Better than usual | 1 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Same as usual | 13 Participants |
| Group A (Antecedent Studies) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Worse than usual | 5 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Good | 29 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Woke up during the night - Yes | 13 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - Friend house | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Woke up during the night - No | 64 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Very Good | 27 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 0 | 2 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Better than usual | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 1 | 10 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week a typical week - Yes | 66 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 2 | 2 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - ill | 2 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 3 | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week a typical week - No | 11 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night = 4 | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Worse than usual | 4 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Number of times woke up per night >= 5 | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - Vacation | 1 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Very Poor | 0 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - other | 1 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Poor | 1 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Past week was not typical - School break | 7 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality of sleep - Average | 20 Participants |
| Group B (Direct Enrollment) | Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) | FoTA: Overall quality - Same as usual | 8 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of investigational product.
Time frame: From start of study drug administration up to follow-up (approximately up to 367 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Antecedent Studies) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 29 Participants |
| Group B (Direct Enrollment) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 38 Participants |
Primary
Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment (FoTA)
CSHQ was a tool designed to screen for the most common sleep problems in children and consisted of 33 items for scoring and several extra items intended to provide administrators with other potentially useful information about respondents. The instrument evaluates the 8 different subscales: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. A 3-point scale was used for rating: usually if the sleep behavior occurs 5 to 7 times per week, sometimes for 2 to 4 times per week, and rarely for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.
Time frame: FoTA (up to 330 days)
Population: Safety set consisted of all participants who had taken at least 1 dose of investigational product in this current study. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment (FoTA) | 42.2 Units on scale | Standard Deviation 8.44 |
| Group B (Direct Enrollment) | Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment (FoTA) | 39.3 Units on scale | Standard Deviation 5.85 |
Secondary
Change From Baseline in Clinician-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Final On-Treatment Assessment (FoTA)
Clinician administered ADHD-RS-5, child, home version total score were analyzed. ADHD-RS-5 consists of 18 items designed to reflect current symptomatology of ADHD based on diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items may be grouped into 2 subscales: hyperactivity/impulsivity (9 items) and inattentiveness (9 items). Higher total scores indicated higher impairment and lower scores indicated no impairment. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date).
Time frame: Baseline, FoTA (up to 330 days)
Population: Full analysis set (FAS) consisted of all participants in the safety set who have completed at least 1 post-dose efficacy assessment using ADHD-RS-5 Total Score. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Change From Baseline in Clinician-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Final On-Treatment Assessment (FoTA) | -19.2 Score on a scale | Standard Error 1.88 |
| Group B (Direct Enrollment) | Change From Baseline in Clinician-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Final On-Treatment Assessment (FoTA) | -19.3 Score on a scale | Standard Error 1.69 |
Secondary
Clinical Global Impression of Improvement (CGI-I) at Final On-Treatment Assessment (FoTA)
CGI-I scale was performed to rate the improvement of a participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date).
Time frame: FoTA (up to 330 days)
Population: FAS consisted of all participants in the safety set who have completed at least 1 post-dose efficacy assessment using ADHD-RS-5 Total Score. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A (Antecedent Studies) | Clinical Global Impression of Improvement (CGI-I) at Final On-Treatment Assessment (FoTA) | 2.7 Score on a scale | Standard Error 0.16 |
| Group B (Direct Enrollment) | Clinical Global Impression of Improvement (CGI-I) at Final On-Treatment Assessment (FoTA) | 2.9 Score on a scale | Standard Error 0.15 |