A Phase 4 interventional study of Guanfacine hydrochloride (TAK-503) and Atomoxetine hydrochloride in Attention Deficit Hyperactivity Disorder, sponsored by Shire. Completed at 50 sites in 9 countries. Open to participants aged 6 Years to 17 Years. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by Shire · Phase 4, Interventional, and Treatment
The main aim of this study is learn more about long-term TAK-503 treatment in children and teenagers with ADHD for whom earlier stimulant treatment did not work.
The study has two parts (A and B). In Part A, participants will take tablets of TAK-503, atomoxetine or placebo and in Part B TAK-503 tablets.
This study will be conducted in two parts Part A and Part B. Part A is a double-blinded, double-dummy, placebo-controlled study with an atomoxetine arm as an active reference to TAK-503. Eligible participants with ADHD will be randomized in a 1:1:1 ratio among TAK-503, atomoxetine, and placebo treatment arms up to 49 weeks of double-blinded treatment. Upon completion of Part A, participants will roll over to Part B directly as per the study protocol directions for an additional 52 weeks of open-label TAK-503 treatment.
Study Part A:
Study Part B:
Exclusion Criteria:
Study Part A:
Participant has a current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder (except oppositional defiant disorder), including but not limited to any of the following comorbid Axis I and Axis II disorders (the K-SADS-PL should be reviewed to confirm diagnosis, if necessary):
Study Part B:
Participants randomized to TAK-503 will receive initial dose of 1 milligram (mg), and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet once daily (QD) for 18 weeks.
Drug: Guanfacine hydrochloride (TAK-503)
Participants who weigh less than (\<) 70 kilograms (kg) at baseline will receive Atomoxetine hydrochloride capsule orally at an initial dose of 0.5 milligram per kilogram (mg/kg) which may be increased to the target dose of 1.2 mg/kg oral capsule QD during the treatment of 18 weeks. Permitted doses of Atomoxetine hydrochloride capsule will be 10, 18, 25, 40, 60, and 80 mg QD. Participants who weigh \>= 70 kg at baseline will receive Atomoxetine hydrochloride at an initial dose of 40 mg oral capsule QD which may be increased to 80 mg and then to 100 mg for 18 weeks. The total dose for participants who weigh \>= 70 kg at baseline will not exceed 100 mg.
Drug: Atomoxetine hydrochloride
Participants aged 6 to 12 years will receive a dose of 1 to 4 mg tablet of placebo matched to TAK-503 and aged 13 to 17 years will receive a dose of 5 to 7 mg tablets of placebo matched to TAK-503 orally QD for 18 weeks. Participants who weigh \< 70 kg at baseline will receive placebo matched to Atomoxetine hydrochloride oral capsule at an initial dose of 0.5 mg/kg which may be increased to the target dose of 1.2 mg/kg QD oral capsule during the treatment of 18 weeks. Permitted doses of placebo matched to Atomoxetine hydrochloride will be 10, 18, 25, 40, 60, and 80 mg QD and participants who weigh \>= 70 kg will receive placebo matched to Atomoxetine hydrochloride at an initial dose of 40 mg QD capsule orally which may be increased to 80 mg and then to 100 mg.
Other: Placebo
Participants from Part A will roll over into Part B directly after 18 weeks and will receive TAK-503 at an initial dose of 1 mg, and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet QD for 52 weeks of Part B.
Drug: Guanfacine hydrochloride (TAK-503)
Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablets once daily for 18 weeks in Part A or 52 weeks in Part B.
Also known as: Intuniv, SPD503
Participants will receive Atomoxetine hydrochloride oral capsule once daily for 18 weeks in Part A.
Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg placebo matched to TAK 503 oral tablets once daily for 18 weeks and placebo matched to atomoxetine hydrochloride oral capsules at once daily for 18 weeks in Part A.
Part A: Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI) Task at Week 18
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circles for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in milliseconds (msec) ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
Time frame: At Baseline, Week 18
Part A: Change From Baseline in the CANTAB RTI Task at Week 49
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
Time frame: At Baseline, Week 49
Part B: Change From Baseline in the CANTAB RTI Task at Week 49
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
Time frame: At Baseline, Week 49
Part A: Change From Baseline in the Rapid Visual Information Processing (RVP) Task of the CANTAB: Mean Response Latency
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Mean Response Latency was defined as the mean response time on trials where participants responded correctly. Higher time indicated worse performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the RVP Task of the CANTAB: Mean Response Latency
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Mean Response Latency was defined as the mean response time on trials where participants responded correctly. Higher time indicated worse performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the RVP Task of the CANTAB: A'
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. A' was defined as the standardized score for target sequence detection, ranging from 0-1. Higher score indicated better performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the RVP Task of the CANTAB: A'
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. A' was defined as the standardized score for target sequence detection, ranging from 0-1. Higher score indicated better performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Probability of Hit was defined as proportion of correct sequence responses divided by total number of sequences. Higher rate indicates better performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Probability of Hit was defined as proportion of correct sequence responses divided by total number of sequences. Higher rate indicates better performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the Spatial Working Memory (SWM) Task of the CANTAB
The ability to retain spatial information and manipulate remembered items in working memory was measured with SWM task. Task was self-ordered and assessed the individual's ability to strategize heuristically. The test was a sensitive measure of frontal lobe and executive dysfunction. The test began with a number of colored squares (boxes) shown on the screen. By selecting the boxes and using a process of elimination, the participant should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The outcome measures to be presented for each assessment of the task as follows: Total errors- number of times a box was selected that was certain to not have any tokens, across all trials ranging 0 (very good) to 66 (poor/impaired). Strategy (6 to 8 boxes)- number of times a participant begins a new search pattern from same box they started with previously, ranging 0 to 13. Higher score indicated a very poor strategy.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the SWM Task of the CANTAB
The ability to retain spatial information and manipulate remembered items in working memory was measured with SWM task. Task was self-ordered and assessed the individual's ability to strategize heuristically. The test was a sensitive measure of frontal lobe and executive dysfunction. The test began with a number of colored squares (boxes) shown on the screen. By selecting the boxes and using a process of elimination, the participant should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The outcome measures to be presented for each assessment of the task as follows: Total errors- number of times a box was selected that was certain to not have any tokens, across all trials ranging 0 (very good) to 66 (poor/impaired). Strategy (6 to 8 boxes) - number of times a participant begins a new search pattern from same box they started with previously, ranging 0 to 13. Higher score indicated a very poor strategy.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the Stop Signal Task (SST) Task of the CANTAB: Stop Signal Reaction Time and Median Reaction Time
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Stop signal reaction time was defined as the estimate of time where an individual can successfully inhibit responses 50 percent (%) of the time. Median reaction time (All Go Trials) was defined as the median reaction time taken across all Go trials within an assessment. Higher time indicated worse performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the SST Task of the CANTAB: Stop Signal Reaction Time and Median Reaction Time
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Stop signal reaction time was defined as the estimate of time where an individual can successfully inhibit responses 50% of the time. Median reaction time (All Go Trials) was defined as the median reaction time taken across all Go trials within an assessment. Higher time indicated worse performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the SST Task of the CANTAB: Direction Error (Go Trials), Direction Error (Stop Trials) and Missed Trials
The neurocognitive function effects of TAK-503 on adolescents and children was evaluated using the CANTAB assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Direction Error (Go Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Go" trial. Direction Error (Stop Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Stop" trial. Missed Trials was defined as the total number of trials which the participant missed. Higher value indicated worse performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the SST Task of the CANTAB: Direction Error (Go Trials), Direction Error (Stop Trials) and Missed Trials
The neurocognitive function effects of TAK-503 on adolescents and children was evaluated using the CANTAB assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Direction Error (Go Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Go" trial. Direction Error (Stop Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Stop" trial. Missed Trials was defined as the total number of trials which the participant missed. Higher value indicated worse performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the Delayed Matching to Sample (DMS) Task of the CANTAB: Percentage of Correct Responses
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Percentage of Correct Responses was defined as the percentage of trials during which the participant chose the correct response on the first attempt. Higher rate indicated better performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the DMS Task of the CANTAB: Percentage of Correct Responses
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Percentage of Correct Responses was defined as the percentage of trials during which the participant chose the correct response on the first attempt. Higher rate indicated better performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the DMS Task of the CANTAB: Mean Correct Latency
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean Correct Latency was defined as the average time between the presentation of the response stimuli objects and the participants selecting the correct box on their first attempt. Higher time indicated worse performance.
Time frame: Baseline, Week 18 and 49
Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Correct Latency
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean Correct Latency was defined as the average time between the presentation of the response stimuli objects and the participants selecting the correct box on their first attempt. Higher time indicated worse performance.
Time frame: Baseline, Week 49
Part A: Change From Baseline in the DMS Task of the CANTAB: Mean Choices to Correct
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean choices to correct was defined as the mean number of choices that the participant made on each trial, including the correct choice. Higher number of choices indicated worse performance.
Time frame: Baseline, Weeks 18 and 49
Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Choices to Correct
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean choices to correct was defined as the mean number of choices that the participant made on each trial, including the correct choice. Higher number of choices indicated worse performance.
Time frame: Baseline, Week 49
Parts A and B: Sexual Maturation Assessed Using Tanner Stage
The stage of puberty or sexual maturation was evaluated for each participant according to Tanner staging. The Tanner stage for genitals (male, stages I-V), breasts (females, stages I-V), and pubic hair (both sexes, stages I-V) was documented. Tanner staging was self-assessed. Self-assessment in this study was defined as participants or parents indicating which drawing of the scale corresponds to participants sexual maturation stage at the time of the specific visit.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Change From Baseline in Weight
Weight was measured in kg using a calibrated scale.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Change From Baseline in Height
A calibrated stadiometer was used for all height measurements and was measured in centimeter (cm).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Change From Baseline in Body Mass Index (BMI)
BMI was a measure of body fat based on height and weight. BMI = (weight in kg x10,000)/(height in cm\^2).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Number of Participants With Clinically Significant Changes in Vital Signs: Pulse Rate, Blood Pressure (BP), Temperature, and Respiratory Rate
Vital signs assessments included pulse rate (beats/minutes), supine and standing BP (millimeters of mercury \[mmHg\]), oral or tympanic temperature (degrees Celsius \[C\]), and respiratory rate (breaths per minute). The number of participants was calculated based on number of participants with non-missing results for a given parameter at Baseline and at least 1 post-Baseline assessment.
Time frame: Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53)
Parts A and B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
The heart rate (HR), PR interval, QRS interval, and QT interval were measured from all ECGs and the QTcB and QTcF were assessed.
Time frame: Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53)
Parts A and B: 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 that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsened in either intensity or frequency following exposure to the investigational product or medicinal product. TEAEs were defined as AEs whose onset occurs, severity worsens, or intensity increases after receiving the blinded trial intervention and up to 3 days after the last dose of double-blind trial medication.
Time frame: Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53)
Part A: Psychiatric Symptoms Assessed Using Brief Psychiatric Rating Scale for Children (BPRS-C): Total Score
Psychiatric symptoms were measured by the BPRS-C. The 21 items were grouped across 7 scales: Behavior Problems \[Questions 1 to 3\], Depression \[Questions 4 to 6\], Thinking Disturbance \[Questions 7 to 9\], Psychomotor Excitation \[Questions 10 to 12\], Withdrawal \[Questions 13 to 15\], Anxiety \[Questions 16 to 18\] and Organicity \[Questions 19 to 21\]. Each of the 21 items was rated on a 7-point severity Likert scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6). A total score was calculated by summing the values across the 21 items, ranging from 0 to 126. Higher scores indicated higher severity.
Time frame: Baseline, Weeks 18 and 49
Part B: Psychiatric Symptoms Assessed Using BPRS-C: Total Score
Psychiatric symptoms were measured by the BPRS-C. The 21 items were grouped across 7 scales: Behavior Problems \[Questions 1 to 3\], Depression \[Questions 4 to 6\], Thinking Disturbance \[Questions 7 to 9\], Psychomotor Excitation \[Questions 10 to 12\], Withdrawal \[Questions 13 to 15\], Anxiety \[Questions 16 to 18\] and Organicity \[Questions 19 to 21\]. Each of the 21 items was rated on a 7-point severity Likert scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6). A total score was calculated by summing the values across the 21 items, ranging from 0 to 126. Higher scores indicated higher severity.
Time frame: Baseline, Weeks 23, 36 and 49
Parts A and B: Number of Participants With Suicidal Ideation (SI) or Behavior Assessed Using Columbia- Suicide Severity Rating Scale (CSSRS)
The C-SSRS was a structured tool used to assess SI and behavior. A maximum of 19 items were completed as follows: 7 items were required, a potential 10 additional items were completed upon a positive response to a required item, and 2 items were completed if suicide or suicide-like behavior was observed during the interview. Suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Score of 1 or higher= suicidal ideation/behavior. Only non-zero categories were reported.
Time frame: Baseline up to Week 52
Parts A and B: Number of Participants With Side Effects Assessed Using Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale: Asthenia or Lassitude or Increased Fatigability
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52
Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Sleepiness or Sedation
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52
Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Increased Duration of Sleep
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52
Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Orthostatic Dizziness
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52
Part A: Sedative Effects Assessed Using Pediatric Daytime Sleepiness Scale (PDSS): Total Score
The PDSS was a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions were based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions were scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS was derived by summing the values from the 8 questions and ranged from 0 (never sleepy) to 32 (always sleepy), with higher scores representing greater severity of excessive sleepiness.
Time frame: Baseline, Weeks 18 and 49
Part B: Sedative Effects Assessed Using PDSS: Total Score
The PDSS was a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions were based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions were scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS was derived by summing the values from the 8 questions and ranged from 0 (never sleepy) to 32 (always sleepy), with higher scores representing greater severity of excessive sleepiness.
Time frame: Baseline, Weeks 23, 36 and 49
Parts A and B: Symptoms Assessed Using ADHD-Rating Scale-5 (ADHD-RS-5): Total Score
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). Total score was obtained from summing the scores of each item and ranged from 0 to 54. Higher score indicated a worse outcome.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Symptoms Assessed Using ADHD-RS-5: Inattention Subscale Score
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The ADHD-RS-5 subscale scores ranged from 0 to 27. Higher score indicated a worse outcome.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Symptoms Assessed Using ADHD-RS-5: Hyperactivity-Impulsivity Subscale Score
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The ADHD-RS-5 subscale scores ranged from 0 to 27. Higher score indicated a worse outcome.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49
Parts A and B: Number of Participants Assessed for Severity of Mental Illness Using Clinical Global Impression-Improvement (CGI-I)
Global clinical measurement of ADHD improvement as measured by CGI-I using the Clinical Global Impression-Severity (CGI-S) to establish baseline. The CGI-S was administered to assess the severity of mental illness at baseline. The CGI-I was administered to assess any improvement in symptoms and to guide the clinician on dosing adjustments. The CGI-I was scored on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher score indicated worst improvement.
Time frame: Part A: Baseline, Weeks 1, 18 and 49; Part B: Baseline, Weeks 23, 36 and 49
Parts A and B: Participants Functioning and Well-being Assessed Using Child Health and Illness Profile - Child Edition: Parent Report Form (CHIP-CE:PRF): Global Score
Parent Report Form of CHIP-CE:PRF was administered to provide information on self-esteem \& school functioning. The 5 domains, 12 subdomains covered 76 items: Satisfaction: with health (7items)\& self (4items); Comfort: physical (9items)\& emotional symptoms (9items) \& activity restrictions (4items) due to illness; Resilience: behaviors\& family involvement (8items) in activities likely to enhance health, Social problem-solving (5items),Physical activity (6items); Risk avoidance: behaviors that if not avoided are likely to pose risks to health: Individual risk avoidance (4items), Threats to achievement (10items); Achievement: developmentally appropriate role functioning in school \& with peers: Academic performance (5items), Peer relations (5items). For each domain/subdomain, means were calculated by taking average of each non-missing item in domain/subdomain. Global score was an average of scores for 5 domains. Each item uses a 5-response format (scored 1-5). Higher score=greater health.
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36 and 49
Parts A and B: Behavioral, Social, and Academic Issues Assessed Using Conners 3 Parent Short Form (C3PS): Total Score
The Conners 3 was a focused tool for the assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3PS was completed by a child's parent/guardian and comprised of 45 items with subsets of items related to six content scales: inattention, hyperactivity/impulsivity, executive functioning, learning problems, defiance/aggression and peer relations. The parent rated his/her child on the first 43 items of the C3PS using a 4-point Likert scale (0-3; where 0=not at all true \[never, seldom\] and 3=very much true \[very often, very frequently\]) based on past month; the last 2 items were fill-in-the-blank and do not contribute to the raw score(s). Total scores were evaluated by summing the 43 numeric items, resulting in a range of 0 to 129, where higher score indicated a greater frequency of issues
Time frame: Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36 and 49
Participants took part in the study at 29 investigative sites in Austria, Belgium, Germany, Netherlands, Portugal, Spain and the United States of America from 18 September 2019 to 02 September 2025. A total of 396 participants were screened, of which 288 were randomized and 108 were screen failures.
| Milestone | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Started | 96 | 96 | 96 | 0 | 0 | 0 |
| Treated participants in double-blinded period | 96 | 96 | 95 | 0 | 0 | 0 |
| Completed | 65 | 38 | 35 | 0 | 0 | 0 |
| Not completed | 31 | 58 | 61 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 13 | 18 | 26 | 0 | 0 | 0 |
| Withdrew: Adverse event | 5 | 15 | 8 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 5 | 4 | 5 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 3 | 3 | 2 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 1 | 3 | 0 | 0 | 0 |
| Withdrew: Other | 5 | 17 | 17 | 0 | 0 | 0 |
| Milestone | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 65 | 29 | 32 |
| Treated participants in open-label period | 0 | 0 | 0 | 63 | 28 | 30 |
| Completed | 0 | 0 | 0 | 36 | 18 | 23 |
| Not completed | 0 | 0 | 0 | 29 | 11 | 9 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 17 | 7 | 4 |
| Withdrew: Adverse event | 0 | 0 | 0 | 4 | 1 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 3 | 2 | 0 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 2 | 0 | 0 |
| Withdrew: Other | 0 | 0 | 0 | 1 | 0 | 1 |
| Withdrew: Not treated in open-label period | 0 | 0 | 0 | 2 | 1 | 2 |
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circles for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in milliseconds (msec) ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
| msec | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18: RTI Mean Five-Choice Reaction Time | -7.1 ± 17.76 | -9.2 ± 17.71 | -5.1 ± 17.67 |
| Change at Week 18: RTI Mean Five-Choice Movement Time | 5.3 ± 10.01 | -10.6 ± 9.92 | -2.5 ± 9.94 |
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
| msec | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|
| Change at Week 49: RTI Mean Five-Choice Reaction Time | -41.6 ± 18.22 | 29.2 ± 18.55 |
| Change at Week 49: RTI Mean Five-Choice Movement Time | -18.6 ± 10.94 | 9.5 ± 11.41 |
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
| msec | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Change at Week 49: RTI Mean Five-Choice Reaction Time | -10.43 ± 245.608 | 12.94 ± 108.468 | -18.81 ± 134.074 |
| Change at Week 49: RTI Mean Five-Choice Movement Time | -17.76 ± 114.942 | -8.08 ± 69.442 | -6.69 ± 57.913 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Mean Response Latency was defined as the mean response time on trials where participants responded correctly. Higher time indicated worse performance.
| msec | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Mean Response Latency | -21.8 ± 24.94 | 28.1 ± 24.60 | -21.0 ± 26.61 |
| Change at Week 49 in Mean Response Latency | — | 48.3 ± 26.03 | -27.1 ± 29.38 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Mean Response Latency was defined as the mean response time on trials where participants responded correctly. Higher time indicated worse performance.
| msec | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the RVP Task of the CANTAB: Mean Response Latency | 89.91 ± 303.686 | -82.75 ± 206.987 | -11.49 ± 270.971 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. A' was defined as the standardized score for target sequence detection, ranging from 0-1. Higher score indicated better performance.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in CANTAB A' | 0.014 ± 0.0113 | 0.029 ± 0.0110 | 0.028 ± 0.0119 |
| Change at Week 49 in CANTAB A' | — | 0.021 ± 0.0141 | 0.019 ± 0.0161 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. A' was defined as the standardized score for target sequence detection, ranging from 0-1. Higher score indicated better performance.
| score on a scale | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the RVP Task of the CANTAB: A' | -0.039 ± 0.0992 | 0.030 ± 0.1044 | 0.040 ± 0.1022 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Probability of Hit was defined as proportion of correct sequence responses divided by total number of sequences. Higher rate indicates better performance.
| proportion | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Probability of Hit | -0.012 ± 0.0279 | 0.035 ± 0.0275 | -0.004 ± 0.0288 |
| Change at Week 49 in Probability of Hit | — | 0.019 ± 0.0299 | 0.002 ± 0.0331 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. RVP measured the ability to sustain attention over time and was a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo-random order at a rate of 100 digits per minute in a box at the center of the screen. Participants were to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen. Probability of Hit was defined as proportion of correct sequence responses divided by total number of sequences. Higher rate indicates better performance.
| proportion | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit | 0.003 ± 0.2589 | 0.106 ± 0.2444 | 0.035 ± 0.2107 |
The ability to retain spatial information and manipulate remembered items in working memory was measured with SWM task. Task was self-ordered and assessed the individual's ability to strategize heuristically. The test was a sensitive measure of frontal lobe and executive dysfunction. The test began with a number of colored squares (boxes) shown on the screen. By selecting the boxes and using a process of elimination, the participant should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The outcome measures to be presented for each assessment of the task as follows: Total errors- number of times a box was selected that was certain to not have any tokens, across all trials ranging 0 (very good) to 66 (poor/impaired). Strategy (6 to 8 boxes)- number of times a participant begins a new search pattern from same box they started with previously, ranging 0 to 13. Higher score indicated a very poor strategy.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Total Errors | -4.6 ± 1.14 | -2.4 ± 1.14 | -2.1 ± 1.14 |
| Change at Week 49 in Total Errors | — | -1.0 ± 1.31 | -1.4 ± 1.33 |
| Change at Week 18 in Strategy (6-8) Boxes | -1.0 ± 0.29 | -0.5 ± 0.29 | -0.8 ± 0.29 |
| Change at Week 49 in Strategy (6-8) Boxes | — | -0.5 ± 0.34 | -0.6 ± 0.35 |
The ability to retain spatial information and manipulate remembered items in working memory was measured with SWM task. Task was self-ordered and assessed the individual's ability to strategize heuristically. The test was a sensitive measure of frontal lobe and executive dysfunction. The test began with a number of colored squares (boxes) shown on the screen. By selecting the boxes and using a process of elimination, the participant should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The outcome measures to be presented for each assessment of the task as follows: Total errors- number of times a box was selected that was certain to not have any tokens, across all trials ranging 0 (very good) to 66 (poor/impaired). Strategy (6 to 8 boxes) - number of times a participant begins a new search pattern from same box they started with previously, ranging 0 to 13. Higher score indicated a very poor strategy.
| score on a scale | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Change at Week 49 in Total Errors | 1.37 ± 7.612 | 5.45 ± 9.567 | -2.59 ± 10.870 |
| Change at Week 49 in Strategy (6-8) Boxes | -0.06 ± 2.508 | 0.35 ± 2.720 | 0.45 ± 3.320 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Stop signal reaction time was defined as the estimate of time where an individual can successfully inhibit responses 50 percent (%) of the time. Median reaction time (All Go Trials) was defined as the median reaction time taken across all Go trials within an assessment. Higher time indicated worse performance.
| msec | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Stop Signal Reaction Time | -5.4 ± 11.42 | 6.9 ± 11.35 | -5.3 ± 11.73 |
| Change at Week 49 in Stop Signal Reaction Time | — | 13.5 ± 13.65 | 9.9 ± 14.19 |
| Change at Week 18 in Median Reaction Time | -14.7 ± 14.83 | -24.0 ± 14.52 | -21.1 ± 14.86 |
| Change at Week 49 in Median Reaction Time | — | -5.6 ± 12.22 | -8.1 ± 12.77 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Stop signal reaction time was defined as the estimate of time where an individual can successfully inhibit responses 50% of the time. Median reaction time (All Go Trials) was defined as the median reaction time taken across all Go trials within an assessment. Higher time indicated worse performance.
| msec | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Change at Week 49 in Stop Signal Reaction Time | 22.87 ± 109.371 | 29.54 ± 121.408 | 49.52 ± 87.175 |
| Change at Week 49 in Median Reaction Time | 18.74 ± 127.049 | 41.68 ± 62.902 | -15.26 ± 82.575 |
The neurocognitive function effects of TAK-503 on adolescents and children was evaluated using the CANTAB assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Direction Error (Go Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Go" trial. Direction Error (Stop Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Stop" trial. Missed Trials was defined as the total number of trials which the participant missed. Higher value indicated worse performance.
| number of trials | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Direction Error (Go Trials) | 3.5 ± 2.73 | 2.5 ± 2.71 | 2.5 ± 2.77 |
| Change at Week 49 in Direction Error (Go Trials) | — | 4.0 ± 3.87 | -3.9 ± 3.95 |
| Change at Week 18 in Direction Error (Stop Trials) | 0.5 ± 1.37 | 1.7 ± 1.37 | 0.2 ± 1.40 |
| Change at Week 49 in Direction Error (Stop Trials) | — | 2.3 ± 1.47 | 0.9 ± 1.51 |
| Change at Week 18 in Missed Trials | 7.4 ± 5.14 | -5.4 ± 5.15 | 2.6 ± 5.20 |
| Change at Week 49 in Missed Trials | — | -9.2 ± 5.19 | -4.5 ± 5.25 |
The neurocognitive function effects of TAK-503 on adolescents and children was evaluated using the CANTAB assessments. SST measured response inhibition or control. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone was present, the participant should not respond. Direction Error (Go Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Go" trial. Direction Error (Stop Trials) was defined as the total number of trials where the participant pressed the wrong button to the direction of the arrow stimulus on a "Stop" trial. Missed Trials was defined as the total number of trials which the participant missed. Higher value indicated worse performance.
| number of trials | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Change at Week 49 in Direction Error (Go Trials) | -1.56 ± 21.394 | -1.05 ± 16.564 | -4.14 ± 12.599 |
| Change at Week 49 in Direction Error (Stop Trials) | -1.21 ± 13.557 | -1.60 ± 9.511 | 3.71 ± 10.267 |
| Change at Week 49 in Missed Trials | 3.18 ± 62.096 | 2.95 ± 28.478 | -10.19 ± 42.487 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Percentage of Correct Responses was defined as the percentage of trials during which the participant chose the correct response on the first attempt. Higher rate indicated better performance.
| percentage | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Percentage of Correct Responses | -0.9 ± 1.83 | 3.3 ± 1.79 | 0.4 ± 1.86 |
| Change at Week 49 in Percentage of Correct Responses | — | 1.3 ± 2.05 | -1.2 ± 2.07 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Percentage of Correct Responses was defined as the percentage of trials during which the participant chose the correct response on the first attempt. Higher rate indicated better performance.
| percentage | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the DMS Task of the CANTAB: Percentage of Correct Responses | 7.42 ± 18.419 | -1.50 ± 15.140 | -1.36 ± 17.264 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean Correct Latency was defined as the average time between the presentation of the response stimuli objects and the participants selecting the correct box on their first attempt. Higher time indicated worse performance.
| msec | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 in Mean Correct Latency | -1887.9 ± 577.62 | -1687.3 ± 565.09 | -1076.7 ± 599.67 |
| Change at Week 49 in Mean Correct Latency | — | -1689.5 ± 562.95 | -1342.1 ± 581.26 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean Correct Latency was defined as the average time between the presentation of the response stimuli objects and the participants selecting the correct box on their first attempt. Higher time indicated worse performance.
| msec | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Correct Latency | 54.16 ± 4671.916 | 1216.36 ± 7274.953 | -1724.85 ± 4113.023 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean choices to correct was defined as the mean number of choices that the participant made on each trial, including the correct choice. Higher number of choices indicated worse performance.
| number of choices | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) |
|---|---|---|---|
| Change at Week 18 in Mean Choices to Correct | 0.036 ± 0.0357 | -0.051 ± 0.0350 | 0.005 ± 0.0364 |
| Change at Week 49 in Mean Choices to Correct | — | -0.019 ± 0.0427 | 0.050 ± 0.0429 |
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD was evaluated using the CANTAB cognitive assessments. DMS measured both simultaneous matching and short-term visual memory. The participant was shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample. Mean choices to correct was defined as the mean number of choices that the participant made on each trial, including the correct choice. Higher number of choices indicated worse performance.
| number of choices | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Choices to Correct | -0.168 ± 0.3588 | 0.020 ± 0.3290 | 0.028 ± 0.3224 |
The stage of puberty or sexual maturation was evaluated for each participant according to Tanner staging. The Tanner stage for genitals (male, stages I-V), breasts (females, stages I-V), and pubic hair (both sexes, stages I-V) was documented. Tanner staging was self-assessed. Self-assessment in this study was defined as participants or parents indicating which drawing of the scale corresponds to participants sexual maturation stage at the time of the specific visit.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Male (Genitals): Baseline — Stage I | 15 | 12 | 17 | 7 | 0 | 4 |
| Male (Genitals): Baseline — Stage II | 14 | 15 | 13 | 12 | 0 | 4 |
| Male (Genitals): Baseline — Stage III | 11 | 10 | 7 | 5 | 10 | 1 |
| Male (Genitals): Baseline — Stage IV | 13 | 14 | 10 | 8 | 1 | 5 |
| Male (Genitals): Baseline — Stage V | 3 | 5 | 9 | 4 | 4 | 3 |
| Male (Genitals): Week 18 — Stage I | 7 | 3 | 11 | — | — | — |
| Male (Genitals): Week 18 — Stage II | 14 | 10 | 10 | — | — | — |
| Male (Genitals): Week 18 — Stage III | 7 | 17 | 7 | — | — | — |
| Male (Genitals): Week 18 — Stage IV | 9 | 9 | 11 | — | — | — |
| Male (Genitals): Week 18 — Stage V | 4 | 2 | 5 | — | — | — |
| Male (Genitals): Week 49 — Stage I | — | 2 | 6 | 2 | 0 | 0 |
| Male (Genitals): Week 49 — Stage II | — | 3 | 8 | 5 | 0 | 5 |
| Male (Genitals): Week 49 — Stage III | — | 11 | 3 | 5 | 3 | 2 |
| Male (Genitals): Week 49 — Stage IV | — | 8 | 7 | 6 | 5 | 4 |
| Male (Genitals): Week 49 — Stage V | — | 4 | 3 | 3 | 3 | 2 |
| Male (Pubic Hair): Baseline — Stage I | 17 | 13 | 17 | 8 | 0 | 5 |
| Male (Pubic Hair): Baseline — Stage II | 14 | 14 | 13 | 11 | 1 | 3 |
| Male (Pubic Hair): Baseline — Stage III | 9 | 12 | 7 | 7 | 9 | 2 |
| Male (Pubic Hair): Baseline — Stage IV | 13 | 12 | 10 | 5 | 1 | 5 |
| Male (Pubic Hair): Baseline — Stage V | 3 | 5 | 9 | 5 | 4 | 2 |
| Male (Pubic Hair): Week 18 — Stage I | 8 | 3 | 11 | — | — | — |
| Male (Pubic Hair): Week 18 — Stage II | 14 | 12 | 10 | — | — | — |
| Male (Pubic Hair): Week 18 — Stage III | 8 | 16 | 8 | — | — | — |
| Male (Pubic Hair): Week 18 — Stage IV | 7 | 8 | 11 | — | — | — |
| Male (Pubic Hair): Week 18 — Stage V | 5 | 2 | 4 | — | — | — |
| Male (Pubic Hair): Week 49 — Stage I | — | 2 | 6 | 3 | 0 | 1 |
| Male (Pubic Hair): Week 49 — Stage II | — | 4 | 7 | 4 | 0 | 4 |
| Male (Pubic Hair): Week 49 — Stage III | — | 11 | 5 | 6 | 6 | 2 |
| Male (Pubic Hair): Week 49 — Stage IV | — | 7 | 7 | 5 | 2 | 4 |
| Male (Pubic Hair): Week 49 — Stage V | — | 4 | 2 | 3 | 3 | 2 |
| Female (Breast): Baseline — Stage I | 10 | 14 | 13 | 6 | 0 | 2 |
| Female (Breast): Baseline — Stage II | 4 | 9 | 4 | 2 | 1 | 1 |
| Female (Breast): Baseline — Stage III | 12 | 4 | 7 | 7 | 5 | 1 |
| Female (Breast): Baseline — Stage IV | 4 | 9 | 9 | 4 | 2 | 4 |
| Female (Breast): Baseline — Stage V | 10 | 4 | 6 | 8 | 5 | 5 |
| Female (Breast): Week 18 — Stage I | 7 | 6 | 8 | — | — | — |
| Female (Breast): Week 18 — Stage II | 2 | 6 | 2 | — | — | — |
| Female (Breast): Week 18 — Stage III | 7 | 6 | 6 | — | — | — |
| Female (Breast): Week 18 — Stage IV | 4 | 8 | 8 | — | — | — |
| Female (Breast): Week 18 — Stage V | 9 | 4 | 6 | — | — | — |
| Female (Breast): Week 49 — Stage I | — | 4 | 6 | 3 | 0 | 0 |
| Female (Breast): Week 49 — Stage II | — | 4 | 2 | 3 | 0 | 0 |
| Female (Breast): Week 49 — Stage III | — | 3 | 2 | 2 | 4 | 1 |
| Female (Breast): Week 49 — Stage IV | — | 3 | 5 | 4 | 1 | 3 |
| Female (Breast): Week 49 — Stage V | — | 5 | 7 | 8 | 4 | 7 |
| Female (Pubic Hair): Baseline — Stage I | 11 | 15 | 13 | 7 | 0 | 2 |
| Female (Pubic Hair): Baseline — Stage II | 4 | 7 | 4 | 1 | 3 | 1 |
| Female (Pubic Hair): Baseline — Stage III | 10 | 4 | 7 | 7 | 3 | 2 |
| Female (Pubic Hair): Baseline — Stage IV | 7 | 11 | 9 | 3 | 2 | 3 |
| Female (Pubic Hair): Baseline — Stage V | 8 | 3 | 6 | 9 | 5 | 5 |
| Female (Pubic Hair): Week 18 — Stage I | 8 | 7 | 8 | — | — | — |
| Female (Pubic Hair): Week 18 — Stage II | 1 | 7 | 2 | — | — | — |
| Female (Pubic Hair): Week 18 — Stage III | 7 | 2 | 6 | — | — | — |
| Female (Pubic Hair): Week 18 — Stage IV | 4 | 12 | 8 | — | — | — |
| Female (Pubic Hair): Week 18 — Stage V | 9 | 2 | 6 | — | — | — |
| Female (Pubic Hair): Week 49 — Stage I | — | 4 | 5 | 3 | 0 | 0 |
| Female (Pubic Hair): Week 49 — Stage II | — | 4 | 3 | 4 | 0 | 0 |
| Female (Pubic Hair): Week 49 — Stage III | — | 2 | 3 | 1 | 3 | 1 |
| Female (Pubic Hair): Week 49 — Stage IV | — | 5 | 4 | 3 | 2 | 3 |
| Female (Pubic Hair): Week 49 — Stage V | — | 4 | 7 | 9 | 4 | 7 |
Weight was measured in kg using a calibrated scale.
| kg | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 46.87 ± 17.002 | 46.35 ± 16.410 | 46.09 ± 15.979 | 47.06 ± 16.989 | 47.79 ± 11.854 | 51.17 ± 16.625 |
| Change at Week 18 | 1.40 ± 2.114 | 1.13 ± 1.822 | 0.42 ± 2.540 | — | — | — |
| Change at Week 49 | — | 3.09 ± 3.515 | 1.67 ± 3.423 | 3.05 ± 3.140 | 2.86 ± 2.872 | 3.21 ± 3.898 |
A calibrated stadiometer was used for all height measurements and was measured in centimeter (cm).
| cm | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 151.09 ± 15.843 | 150.77 ± 18.462 | 149.69 ± 17.467 | 151.39 ± 16.459 | 151.98 ± 15.550 | 153.62 ± 16.792 |
| Change at Week 18 | 1.54 ± 1.756 | 1.42 ± 1.505 | 1.25 ± 1.434 | — | — | — |
| Change at Week 49 | — | 2.63 ± 2.838 | 2.71 ± 2.219 | 2.74 ± 2.469 | 3.07 ± 3.099 | 3.52 ± 3.243 |
BMI was a measure of body fat based on height and weight. BMI = (weight in kg x10,000)/(height in cm\^2).
| kilograms per meter square (kg/m^2) | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 19.90 ± 3.908 | 19.78 ± 3.566 | 19.90 ± 3.473 | 19.91 ± 3.773 | 20.41 ± 2.472 | 21.07 ± 3.198 |
| Change at Week 18 | 0.25 ± 0.752 | 0.18 ± 0.688 | -0.11 ± 1.099 | — | — | — |
| Change at Week 49 | — | 0.71 ± 1.063 | 0.09 ± 1.362 | 0.68 ± 1.452 | 0.43 ± 0.890 | 0.43 ± 1.498 |
Vital signs assessments included pulse rate (beats/minutes), supine and standing BP (millimeters of mercury \[mmHg\]), oral or tympanic temperature (degrees Celsius \[C\]), and respiratory rate (breaths per minute). The number of participants was calculated based on number of participants with non-missing results for a given parameter at Baseline and at least 1 post-Baseline assessment.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Pulse Rate: <=50 Beats/minute | 2 | 10 | 0 | 2 | 1 | 2 |
| Pulse Rate: >=100 Beats/minute | 36 | 29 | 38 | 9 | 7 | 5 |
| Supine BP (Systolic): <90 [6-12 years] or <100 mmHg [13-17 years] | 21 | 34 | 14 | 17 | 6 | 5 |
| Supine BP (Systolic): >120 [6-12 years] or >140 mmHg [13-17 years] | 5 | 16 | 9 | 4 | 0 | 1 |
| Supine BP (Diastolic): <50 [6-12 years] or <60 mmHg [13-17 years] | 21 | 27 | 15 | 16 | 4 | 5 |
| Supine BP (Diastolic): >80 [6-12 years] or >90 mmHg [13-17 years] | 8 | 14 | 9 | 6 | 1 | 0 |
| Standing BP (Systolic): >130 mmHg | 3 | 10 | 4 | 1 | 0 | 1 |
| Standing BP (Diastolic): >95 mmHg | 2 | 1 | 5 | 1 | 0 | 0 |
| Temperature | 0 | 0 | 0 | 0 | 0 | 0 |
| Respiratory Rate | 0 | 0 | 0 | 0 | 0 | 0 |
The heart rate (HR), PR interval, QRS interval, and QT interval were measured from all ECGs and the QTcB and QTcF were assessed.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Parts A and B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 1 | 1 | 0 | 0 | 0 | 0 |
An Adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product or medicinal product or any existing event that worsened in either intensity or frequency following exposure to the investigational product or medicinal product. TEAEs were defined as AEs whose onset occurs, severity worsens, or intensity increases after receiving the blinded trial intervention and up to 3 days after the last dose of double-blind trial medication.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 36 | 60 | 58 | 30 | 8 | 13 |
Psychiatric symptoms were measured by the BPRS-C. The 21 items were grouped across 7 scales: Behavior Problems \[Questions 1 to 3\], Depression \[Questions 4 to 6\], Thinking Disturbance \[Questions 7 to 9\], Psychomotor Excitation \[Questions 10 to 12\], Withdrawal \[Questions 13 to 15\], Anxiety \[Questions 16 to 18\] and Organicity \[Questions 19 to 21\]. Each of the 21 items was rated on a 7-point severity Likert scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6). A total score was calculated by summing the values across the 21 items, ranging from 0 to 126. Higher scores indicated higher severity.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 | -3.0 ± 1.06 | -3.1 ± 1.05 | -3.1 ± 1.06 |
| Change at Week 49 | — | -6.0 ± 0.94 | -4.4 ± 0.99 |
Psychiatric symptoms were measured by the BPRS-C. The 21 items were grouped across 7 scales: Behavior Problems \[Questions 1 to 3\], Depression \[Questions 4 to 6\], Thinking Disturbance \[Questions 7 to 9\], Psychomotor Excitation \[Questions 10 to 12\], Withdrawal \[Questions 13 to 15\], Anxiety \[Questions 16 to 18\] and Organicity \[Questions 19 to 21\]. Each of the 21 items was rated on a 7-point severity Likert scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6). A total score was calculated by summing the values across the 21 items, ranging from 0 to 126. Higher scores indicated higher severity.
| score on a scale | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Total Score: Baseline | 11.7 ± 8.86 | 10.6 ± 7.85 | 9.9 ± 9.25 |
| Total Score: Week 23 | 13.2 ± 13.41 | 5.1 ± 4.53 | 8.5 ± 7.33 |
| Total Score: Week 36 | 8.2 ± 7.29 | 5.4 ± 4.14 | 7.7 ± 7.42 |
| Total Score: Week 49 | 7.2 ± 6.87 | 4.2 ± 2.59 | 8.6 ± 9.55 |
The C-SSRS was a structured tool used to assess SI and behavior. A maximum of 19 items were completed as follows: 7 items were required, a potential 10 additional items were completed upon a positive response to a required item, and 2 items were completed if suicide or suicide-like behavior was observed during the interview. Suicidal ideation, including intensity of ideation, behavior, \& attempts with actual/potential lethality. Categories have binary responses (yes/no) \& include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Score of 1 or higher= suicidal ideation/behavior. Only non-zero categories were reported.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Wish to be Dead | 0 | 1 | 0 | 0 | 0 | 0 |
| Non-specific Active Suicidal Thoughts | 0 | 0 | 0 | 1 | 0 | 0 |
| Active SI with Any Methods (Not Plan) Without Intent to Act | 0 | 0 | 0 | 1 | 0 | 0 |
| Active SI with Some Intent to Act, Without Specific Plan | 0 | 0 | 0 | 1 | 0 | 0 |
| Active SI with Specific Plan and Intent | 0 | 0 | 0 | 1 | 0 | 0 |
| Actual Attempt | 0 | 0 | 0 | 1 | 0 | 0 |
| Interrupted Attempts | 0 | 0 | 0 | 1 | 0 | 0 |
| Preparatory Acts or Behavior | 0 | 0 | 0 | 1 | 0 | 0 |
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline — Normal | 83 | 85 | 83 | 54 | 28 | 30 |
| Baseline — Mild | 8 | 6 | 6 | 5 | 0 | 0 |
| Baseline — Moderate | 1 | 2 | 1 | 3 | 0 | 0 |
| Baseline — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline — Missing | 0 | 0 | 1 | 0 | 0 | 0 |
| Week 18 — Normal | 59 | 59 | 62 | — | — | — |
| Week 18 — Mild | 5 | 3 | 4 | — | — | — |
| Week 18 — Moderate | 1 | 4 | 2 | — | — | — |
| Week 18 — Severe | 0 | 2 | 0 | — | — | — |
| Week 18 — Missing | 0 | 0 | 0 | — | — | — |
| Week 23 — Normal | — | — | — | 47 | 25 | 26 |
| Week 23 — Mild | — | — | — | 4 | 0 | 0 |
| Week 23 — Moderate | — | — | — | 3 | 0 | 1 |
| Week 23 — Severe | — | — | — | 0 | 0 | 0 |
| Week 23 — Missing | — | — | — | 0 | 0 | 0 |
| Week 36 — Normal | — | — | — | 41 | 23 | 22 |
| Week 36 — Mild | — | — | — | 5 | 0 | 2 |
| Week 36 — Moderate | — | — | — | 0 | 0 | 1 |
| Week 36 — Severe | — | — | — | 0 | 0 | 0 |
| Week 36 — Missing | — | — | — | 0 | 0 | 0 |
| Week 49 — Normal | — | 67 | 70 | 39 | 23 | 23 |
| Week 49 — Mild | — | 4 | 3 | 3 | 1 | 3 |
| Week 49 — Moderate | — | 5 | 2 | 2 | 0 | 2 |
| Week 49 — Severe | — | 0 | 0 | 0 | 0 | 0 |
| Week 49 — Missing | — | 0 | 1 | 0 | 0 | 0 |
| Week 50 — Normal | — | — | — | 38 | 22 | 24 |
| Week 50 — Mild | — | — | — | 0 | 1 | 1 |
| Week 50 — Moderate | — | — | — | 0 | 0 | 1 |
| Week 50 — Severe | — | — | — | 0 | 0 | 0 |
| Week 50 — Missing | — | — | — | 0 | 0 | 0 |
| Week 51 — Normal | — | — | — | 37 | 23 | 23 |
| Week 51 — Mild | — | — | — | 1 | 0 | 1 |
| Week 51 — Moderate | — | — | — | 0 | 0 | 1 |
| Week 51 — Severe | — | — | — | 0 | 0 | 0 |
| Week 51 — Missing | — | — | — | 0 | 0 | 0 |
| Week 52 — Normal | — | — | — | 38 | 23 | 23 |
| Week 52 — Mild | — | — | — | 0 | 0 | 1 |
| Week 52 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 52 — Severe | — | — | — | 0 | 0 | 0 |
| Week 52 — Missing | — | — | — | 0 | 0 | 0 |
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline — Normal | 84 | 82 | 83 | 56 | 26 | 28 |
| Baseline — Mild | 6 | 6 | 7 | 6 | 1 | 2 |
| Baseline — Moderate | 2 | 5 | 1 | 0 | 1 | 0 |
| Baseline — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline — Missing | 0 | 0 | 0 | 0 | 0 | 0 |
| Week 18 — Normal | 57 | 58 | 62 | — | — | — |
| Week 18 — Mild | 8 | 6 | 6 | — | — | — |
| Week 18 — Moderate | 0 | 3 | 0 | — | — | — |
| Week 18 — Severe | 0 | 1 | 0 | — | — | — |
| Week 18 — Missing | 0 | 0 | 0 | — | — | — |
| Week 23 — Normal | — | — | — | 47 | 25 | 26 |
| Week 23 — Mild | — | — | — | 4 | 0 | 0 |
| Week 23 — Moderate | — | — | — | 3 | 0 | 1 |
| Week 23 — Severe | — | — | — | 0 | 0 | 0 |
| Week 23 — Missing | — | — | — | 0 | 0 | 0 |
| Week 36 — Normal | — | — | — | 43 | 22 | 23 |
| Week 36 — Mild | — | — | — | 1 | 1 | 2 |
| Week 36 — Moderate | — | — | — | 1 | 0 | 0 |
| Week 36 — Severe | — | — | — | 0 | 0 | 0 |
| Week 36 — Missing | — | — | — | 1 | 0 | 0 |
| Week 49 — Normal | — | 64 | 70 | 34 | 21 | 25 |
| Week 49 — Mild | — | 6 | 4 | 6 | 2 | 2 |
| Week 49 — Moderate | — | 6 | 2 | 4 | 1 | 1 |
| Week 49 — Severe | — | 0 | 0 | 0 | 0 | 0 |
| Week 49 — Missing | — | 0 | 0 | 0 | 0 | 0 |
| Week 50 — Normal | — | — | — | 36 | 22 | 25 |
| Week 50 — Mild | — | — | — | 2 | 1 | 1 |
| Week 50 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 50 — Severe | — | — | — | 0 | 0 | 0 |
| Week 50 — Missing | — | — | — | 0 | 0 | 0 |
| Week 51 — Normal | — | — | — | 37 | 22 | 24 |
| Week 51 — Mild | — | — | — | 1 | 1 | 1 |
| Week 51 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 51 — Severe | — | — | — | 0 | 0 | 0 |
| Week 51 — Missing | — | — | — | 0 | 0 | 0 |
| Week 52 — Normal | — | — | — | 36 | 23 | 23 |
| Week 52 — Mild | — | — | — | 1 | 0 | 1 |
| Week 52 — Moderate | — | — | — | 1 | 0 | 0 |
| Week 52 — Severe | — | — | — | 0 | 0 | 0 |
| Week 52 — Missing | — | — | — | 0 | 0 | 0 |
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline — Normal | 89 | 87 | 86 | 54 | 28 | 30 |
| Baseline — Mild | 2 | 4 | 5 | 5 | 0 | 0 |
| Baseline — Moderate | 1 | 2 | 0 | 3 | 0 | 0 |
| Baseline — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Week 18 — Normal | 62 | 62 | 61 | — | — | — |
| Week 18 — Mild | 2 | 3 | 6 | — | — | — |
| Week 18 — Moderate | 1 | 3 | 1 | — | — | — |
| Week 18 — Severe | 0 | 0 | 0 | — | — | — |
| Week 23 — Normal | — | — | — | 50 | 21 | 23 |
| Week 23 — Mild | — | — | — | 2 | 4 | 3 |
| Week 23 — Moderate | — | — | — | 2 | 0 | 1 |
| Week 23 — Severe | — | — | — | 0 | 0 | 0 |
| Week 36 — Normal | — | — | — | 45 | 22 | 24 |
| Week 36 — Mild | — | — | — | 1 | 1 | 1 |
| Week 36 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 36 — Severe | — | — | — | 0 | 0 | 0 |
| Week 49 — Normal | — | 71 | 72 | 39 | 23 | 26 |
| Week 49 — Mild | — | 4 | 3 | 4 | 1 | 1 |
| Week 49 — Moderate | — | 1 | 1 | 1 | 0 | 1 |
| Week 49 — Severe | — | 0 | 0 | 0 | 0 | 0 |
| Week 50 — Normal | — | — | — | 35 | 22 | 24 |
| Week 50 — Mild | — | — | — | 3 | 1 | 2 |
| Week 50 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 50 — Severe | — | — | — | 0 | 0 | 0 |
| Week 51 — Normal | — | — | — | 35 | 22 | 23 |
| Week 51 — Mild | — | — | — | 1 | 1 | 2 |
| Week 51 — Moderate | — | — | — | 2 | 0 | 0 |
| Week 51 — Severe | — | — | — | 0 | 0 | 0 |
| Week 52 — Normal | — | — | — | 34 | 23 | 24 |
| Week 52 — Mild | — | — | — | 4 | 0 | 0 |
| Week 52 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 52 — Severe | — | — | — | 0 | 0 | 0 |
UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of TAK-503 such as Asthenia/Lassitude/lncreased Fatiguability, Sleepiness/Sedation, Increased Duration of Sleep, and Orthostatic Dizziness were queried. Each side effect was categorized for severity, ranging from 0 (Normal) to 3 (Severe).
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline — Normal | 88 | 92 | 89 | 61 | 28 | 30 |
| Baseline — Mild | 2 | 1 | 2 | 1 | 0 | 0 |
| Baseline — Moderate | 2 | 0 | 0 | 0 | 0 | 0 |
| Baseline — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Week 18 — Normal | 63 | 62 | 65 | — | — | — |
| Week 18 — Mild | 2 | 6 | 2 | — | — | — |
| Week 18 — Moderate | 0 | 0 | 1 | — | — | — |
| Week 18 — Severe | 0 | 0 | 0 | — | — | — |
| Week 23 — Normal | — | — | — | 52 | 23 | 27 |
| Week 23 — Mild | — | — | — | 0 | 1 | 0 |
| Week 23 — Moderate | — | — | — | 2 | 1 | 0 |
| Week 23 — Severe | — | — | — | 0 | 0 | 0 |
| Week 36 — Normal | — | — | — | 45 | 22 | 23 |
| Week 36 — Mild | — | — | — | 0 | 1 | 2 |
| Week 36 — Moderate | — | — | — | 1 | 0 | 0 |
| Week 36 — Severe | — | — | — | 0 | 0 | 0 |
| Week 49 — Normal | — | 69 | 75 | 41 | 23 | 27 |
| Week 49 — Mild | — | 5 | 1 | 3 | 1 | 1 |
| Week 49 — Moderate | — | 2 | 0 | 0 | 0 | 0 |
| Week 49 — Severe | — | 0 | 0 | 0 | 0 | 0 |
| Week 50 — Normal | — | — | — | 37 | 22 | 26 |
| Week 50 — Mild | — | — | — | 0 | 1 | 0 |
| Week 50 — Moderate | — | — | — | 1 | 0 | 0 |
| Week 50 — Severe | — | — | — | 0 | 0 | 0 |
| Week 51 — Normal | — | — | — | 37 | 22 | 25 |
| Week 51 — Mild | — | — | — | 0 | 1 | 0 |
| Week 51 — Moderate | — | — | — | 1 | 0 | 0 |
| Week 51 — Severe | — | — | — | 0 | 0 | 0 |
| Week 52 — Normal | — | — | — | 38 | 22 | 24 |
| Week 52 — Mild | — | — | — | 0 | 1 | 0 |
| Week 52 — Moderate | — | — | — | 0 | 0 | 0 |
| Week 52 — Severe | — | — | — | 0 | 0 | 0 |
The PDSS was a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions were based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions were scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS was derived by summing the values from the 8 questions and ranged from 0 (never sleepy) to 32 (always sleepy), with higher scores representing greater severity of excessive sleepiness.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine |
|---|---|---|---|
| Change at Week 18 | -2.0 ± 0.56 | -1.8 ± 0.56 | -0.8 ± 0.56 |
| Change at Week 49 | — | -2.0 ± 0.67 | -1.7 ± 0.67 |
The PDSS was a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions were based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions were scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS was derived by summing the values from the 8 questions and ranged from 0 (never sleepy) to 32 (always sleepy), with higher scores representing greater severity of excessive sleepiness.
| score on a scale | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|
| Baseline | 13.2 ± 4.79 | 15.5 ± 4.69 | 15.1 ± 3.56 |
| Week 23 | 13.5 ± 6.12 | 13.3 ± 5.68 | 14.6 ± 4.02 |
| Week 36 | 12.2 ± 5.72 | 12.9 ± 4.16 | 13.3 ± 5.12 |
| Week 49 | 12.5 ± 5.27 | 14.6 ± 5.25 | 13.8 ± 3.76 |
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). Total score was obtained from summing the scores of each item and ranged from 0 to 54. Higher score indicated a worse outcome.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 39.8 ± 8.12 | 39.4 ± 8.29 | 40.0 ± 7.89 | 31.6 ± 12.02 | 24.1 ± 10.08 | 24.6 ± 11.80 |
| Week 18 | 31.3 ± 12.10 | 21.4 ± 9.19 | 21.6 ± 9.26 | — | — | — |
| Week 49 | — | 17.1 ± 6.91 | 17.2 ± 8.54 | 19.3 ± 11.74 | 13.0 ± 4.22 | 16.7 ± 10.11 |
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The ADHD-RS-5 subscale scores ranged from 0 to 27. Higher score indicated a worse outcome.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 21.6 ± 4.17 | 21.5 ± 4.24 | 21.9 ± 4.12 | 17.0 ± 6.55 | 13.0 ± 4.97 | 13.7 ± 6.06 |
| Week 18 | 16.9 ± 6.35 | 11.7 ± 4.78 | 12.4 ± 5.14 | — | — | — |
| Week 49 | — | 9.2 ± 4.41 | 9.7 ± 5.28 | 9.7 ± 6.26 | 7.4 ± 2.78 | 10.3 ± 5.47 |
The ADHD-RS-5 was used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. The ADHD-RS-5 was based on the diagnostic criteria for ADHD as described in the DSM-5 and consisted of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale was scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The ADHD-RS-5 subscale scores ranged from 0 to 27. Higher score indicated a worse outcome.
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 18.2 ± 6.08 | 17.9 ± 6.18 | 18.1 ± 6.26 | 14.6 ± 7.02 | 11.1 ± 6.19 | 10.9 ± 6.65 |
| Week 18 | 14.3 ± 7.29 | 9.6 ± 5.77 | 9.2 ± 5.58 | — | — | — |
| Week 49 | — | 7.9 ± 4.02 | 7.5 ± 5.20 | 9.6 ± 6.31 | 5.6 ± 3.00 | 6.4 ± 5.50 |
Global clinical measurement of ADHD improvement as measured by CGI-I using the Clinical Global Impression-Severity (CGI-S) to establish baseline. The CGI-S was administered to assess the severity of mental illness at baseline. The CGI-I was administered to assess any improvement in symptoms and to guide the clinician on dosing adjustments. The CGI-I was scored on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher score indicated worst improvement.
| Participants | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Week 1 — Very Much Improved | 0 | 2 | 0 | — | — | — |
| Week 1 — Much Improved | 0 | 5 | 5 | — | — | — |
| Week 1 — Minimally Improved | 22 | 23 | 26 | — | — | — |
| Week 1 — No Change | 55 | 46 | 49 | — | — | — |
| Week 1 — Minimally Worse | 5 | 3 | 4 | — | — | — |
| Week 1 — Much Worse | 1 | 0 | 0 | — | — | — |
| Week 1 — Very Much Worse | 0 | 0 | 0 | — | — | — |
| Week 1 — Not Assessed | 0 | 0 | 0 | — | — | — |
| Week 18 — Very Much Improved | 4 | 13 | 11 | — | — | — |
| Week 18 — Much Improved | 14 | 29 | 26 | — | — | — |
| Week 18 — Minimally Improved | 13 | 16 | 22 | — | — | — |
| Week 18 — No Change | 32 | 10 | 12 | — | — | — |
| Week 18 — Minimally Worse | 3 | 2 | 0 | — | — | — |
| Week 18 — Much Worse | 0 | 1 | 1 | — | — | — |
| Week 18 — Very Much Worse | 0 | 0 | 0 | — | — | — |
| Week 18 — Not Assessed | 0 | 0 | 0 | — | — | — |
| Week 23 — Very Much Improved | — | — | — | 15 | 14 | 6 |
| Week 23 — Much Improved | — | — | — | 18 | 9 | 14 |
| Week 23 — Minimally Improved | — | — | — | 14 | 1 | 6 |
| Week 23 — No Change | — | — | — | 3 | 0 | 0 |
| Week 23 — Minimally Worse | — | — | — | 1 | 0 | 0 |
| Week 23 — Much Worse | — | — | — | 0 | 0 | 0 |
| Week 23 — Very Much Worse | — | — | — | 0 | 0 | 0 |
| Week 23 — Not Assessed | — | — | — | 0 | 0 | 0 |
| Week 36 — Very Much Improved | — | — | — | 12 | 11 | 8 |
| Week 36 — Much Improved | — | — | — | 22 | 11 | 13 |
| Week 36 — Minimally Improved | — | — | — | 9 | 0 | 3 |
| Week 36 — No Change | — | — | — | 3 | 0 | 2 |
| Week 36 — Minimally Worse | — | — | — | 0 | 0 | 0 |
| Week 36 — Much Worse | — | — | — | 0 | 0 | 0 |
| Week 36 — Very Much Worse | — | — | — | 0 | 0 | 0 |
| Week 36 — Not Assessed | — | — | — | 0 | 0 | 0 |
| Week 49 — Very Much Improved | — | 19 | 13 | 16 | 12 | 5 |
| Week 49 — Much Improved | — | 21 | 18 | 15 | 8 | 14 |
| Week 49 — Minimally Improved | — | 5 | 14 | 4 | 0 | 3 |
| Week 49 — No Change | — | 1 | 4 | 3 | 0 | 1 |
| Week 49 — Minimally Worse | — | 0 | 0 | 0 | 0 | 0 |
| Week 49 — Much Worse | — | 1 | 0 | 0 | 0 | 0 |
| Week 49 — Very Much Worse | — | 0 | 0 | 0 | 0 | 0 |
| Week 49 — Not Assessed | — | 0 | 0 | 0 | 0 | 1 |
Parent Report Form of CHIP-CE:PRF was administered to provide information on self-esteem \& school functioning. The 5 domains, 12 subdomains covered 76 items: Satisfaction: with health (7items)\& self (4items); Comfort: physical (9items)\& emotional symptoms (9items) \& activity restrictions (4items) due to illness; Resilience: behaviors\& family involvement (8items) in activities likely to enhance health, Social problem-solving (5items),Physical activity (6items); Risk avoidance: behaviors that if not avoided are likely to pose risks to health: Individual risk avoidance (4items), Threats to achievement (10items); Achievement: developmentally appropriate role functioning in school \& with peers: Academic performance (5items), Peer relations (5items). For each domain/subdomain, means were calculated by taking average of each non-missing item in domain/subdomain. Global score was an average of scores for 5 domains. Each item uses a 5-response format (scored 1-5). Higher score=greater health.
| score on scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 3.49 ± 0.351 | 3.58 ± 0.275 | 3.56 ± 0.357 | 3.53 ± 0.405 | 3.78 ± 0.263 | 3.87 ± 0.304 |
| Week 18 | 3.52 ± 0.372 | 3.74 ± 0.293 | 3.81 ± 0.243 | — | — | — |
| Week 23 | — | — | — | 3.70 ± 0.399 | 3.97 ± 0.225 | 3.78 ± 0.308 |
| Week 36 | — | — | — | 3.69 ± 0.387 | 3.99 ± 0.264 | 3.88 ± 0.300 |
| Week 49 | — | 3.83 ± 0.229 | 3.89 ± 0.313 | 3.78 ± 0.387 | 3.98 ± 0.379 | 3.88 ± 0.287 |
The Conners 3 was a focused tool for the assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3PS was completed by a child's parent/guardian and comprised of 45 items with subsets of items related to six content scales: inattention, hyperactivity/impulsivity, executive functioning, learning problems, defiance/aggression and peer relations. The parent rated his/her child on the first 43 items of the C3PS using a 4-point Likert scale (0-3; where 0=not at all true \[never, seldom\] and 3=very much true \[very often, very frequently\]) based on past month; the last 2 items were fill-in-the-blank and do not contribute to the raw score(s). Total scores were evaluated by summing the 43 numeric items, resulting in a range of 0 to 129, where higher score indicated a greater frequency of issues
| score on a scale | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| Baseline | 66.3 ± 16.78 | 63.7 ± 17.52 | 66.0 ± 17.41 | 58.9 ± 24.87 | 40.9 ± 14.35 | 48.9 ± 13.71 |
| Week 18 | 59.8 ± 24.94 | 44.2 ± 16.90 | 45.7 ± 13.57 | — | — | — |
| Week 23 | — | — | — | 43.2 ± 24.92 | 38.2 ± 10.81 | 45.9 ± 14.74 |
| Week 36 | — | — | — | 36.9 ± 23.82 | 34.0 ± 8.89 | 43.4 ± 18.00 |
| Week 49 | — | 34.7 ± 14.12 | 35.0 ± 16.72 | 35.5 ± 20.32 | 35.0 ± 12.01 | 47.2 ± 18.57 |
Collected over Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow up (Week 53). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Double-Blinded Period (Part A): Placebo | 0/96 (0%) | 0/96 (0%) | 27/96 (28.1%) |
| Double-Blinded Period (Part A): TAK-503 | 0/96 (0%) | 0/96 (0%) | 50/96 (52.1%) |
| Double-Blinded Period (Part A): Atomoxetine | 0/95 (0%) | 0/95 (0%) | 49/95 (51.6%) |
| Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | 0/63 (0%) | 1/63 (1.6%) | 25/63 (39.7%) |
| Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | 0/28 (0%) | 0/28 (0%) | 8/28 (28.6%) |
| Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) | 0/30 (0%) | 0/30 (0%) | 12/30 (40%) |
| Event | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| AppendicitisInfections and infestations | 0/96 | 0/96 | 0/95 | 1/63 | 0/28 | 0/30 |
| Event | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Open-Label Period (Part B): Part A (Placebo) - Part B (TAK-503) | Open-Label Period (Part B): Part A (TAK-503) - Part B (TAK-503) | Open-Label Period (Part B): Part A (Atomoxetine) - Part B (TAK-503) |
|---|---|---|---|---|---|---|
| SomnolenceNervous system disorders | 8/96 | 20/96 | 8/95 | 11/63 | 3/28 | 2/30 |
| HeadacheNervous system disorders | 6/96 | 14/96 | 12/95 | 6/63 | 1/28 | 2/30 |
| FatigueGeneral disorders | 3/96 | 10/96 | 5/95 | 9/63 | 1/28 | 1/30 |
| NauseaGastrointestinal disorders | 1/96 | 3/96 | 12/95 | 0/63 | 0/28 | 0/30 |
| Decreased appetiteMetabolism and nutrition disorders | 3/96 | 5/96 | 11/95 | 0/63 | 0/28 | 1/30 |
| Abdominal painGastrointestinal disorders | 0/96 | 3/96 | 3/95 | 1/63 | 0/28 | 3/30 |
| NasopharyngitisInfections and infestations | 1/96 | 3/96 | 3/95 | 0/63 | 1/28 | 3/30 |
| DizzinessNervous system disorders | 6/96 | 7/96 | 9/95 | 5/63 | 1/28 | 0/30 |
| Abdominal pain upperGastrointestinal disorders | 4/96 | 5/96 | 8/95 | 1/63 | 0/28 | 0/30 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 0/96 | 7/96 | 2/95 | 1/63 | 0/28 | 1/30 |
The double-blind safety set included all randomized participants in Study Part A who received \>=1 intervention dose.
| Age, Continuous(years) | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Total |
|---|---|---|---|---|
| Mean | 11.4 ± 3.06 | 11.1 ± 3.24 | 11.1 ± 3.11 | 11.2 ± 3.13 |
| Sex: Female, Male(Participants) | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Total |
|---|---|---|---|---|
| Female | 40 | 40 | 39 | 119 |
| Male | 56 | 56 | 56 | 168 |
| Ethnicity (NIH/OMB)(Participants) | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Total |
|---|---|---|---|---|
| Hispanic or Latino | 37 | 39 | 36 | 112 |
| Not Hispanic or Latino | 59 | 57 | 59 | 175 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Double-Blinded Period (Part A): Placebo | Double-Blinded Period (Part A): TAK-503 | Double-Blinded Period (Part A): Atomoxetine | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 1 | 1 |
| Asian | 0 | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 0 | 1 |
| Black or African American | 30 | 35 | 31 | 96 |
| White | 64 | 58 | 59 | 181 |
| More than one race | 0 | 2 | 3 | 5 |
| Unknown or Not Reported | 1 | 1 | 0 | 2 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting information: Study protocol, Sap, Icf, Csr
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Attention Deficit Disorder with Hyperactivity→
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