Safety and Tolerability Study of SHP465 in Children Aged 4 to 12 Years Diagnosed With Attention-deficit/Hyperactivity Disorder (ADHD)
- Registration Number
- NCT03325894
- Lead Sponsor
- Shire
- Brief Summary
The purpose of the study is to evaluate the long-term safety and tolerability of SHP465 at 6.25 milligram (mg) in children aged 4 to 12 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 141
- Participant is male or female aged 4-12 years inclusive at the time of consent.
- Participant's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (as applicable) by the participant.
- Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (any subtype).
- Participant who is a female and of child-bearing potential must not be pregnant and agree to comply with any applicable contraceptive requirements..
- Participant has an ADHD-RS-5 Child, Home Version Total Score of greater than or equal to (>=) 28 and Clinical Global Impression - Severity of Illness (CGI-S) score >=4 at baseline (Visit 2). Participant is currently not on ADHD therapy, or is not completely satisfied with their current ADHD therapy.
- Participant is required or anticipated to take medications that have central nervous system effects or affect performance. Stable use of bronchodilator inhalers is not exclusionary.
- Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the participant. - Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
- Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy.
- Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
- Participant has a blood pressure measurement >=95th percentile for age, sex, and height at screening (Visit 1) and/or baseline (Visit 2).
- Participant has a height less than or equal to (<=) 5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2).
- Participant has a weight <=5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2).
- Participant has a known history of symptomatic cardiovascular disease, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac conditions placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
- Participant has a history of seizures (other than infantile febrile seizures).
- Participant is taking any medication that is excluded per the protocol.
- Participant had any clinically significant ECG or clinical laboratory abnormalities at the screening (Visit 1) or baseline visit (Visit 2).
- Participant has current abnormal thyroid function, defined as abnormal thyroid-stimulating hormone and thyroxine at the screening or baseline visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
- Participant is currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or currently demonstrating suicidal ideation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SHP465 SHP465 Group A participants who have been rolled-over from antecedent SHP465 studies and Group B participants who will be newly enrolled into the study will receive SHP465 capsule 6.25 mg orally once daily for 360 days.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From start of study drug administration up to follow-up (approximately up to 367 days) An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of investigational product.
Change From Baseline in Pulse Rate at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Change from baseline in pulse rate at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Change From Baseline in Blood Pressure at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at FoTA was reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Change From Baseline in Height at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Height was measured in centimeters (cm) without shoes and with light clothing using a stadiometer. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Change From Baseline in Weight at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Weight was measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product in the current study.
Change From Baseline in Hematology Parameters at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils band form, segmented neutrophils, neutrophils/total cells and platelets were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Leukocytes at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology leukocytes parameter: basophils, eosinophils, lymphocytes, monocytes and neutrophil were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Erythrocytes at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter erythrocytes were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin Concentration at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin concentration were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter erythrocytes mean corpuscular hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Chemistry Parameters (Albumin and Protein) at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in chemistry parameters albumin and protein were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Chemistry Parameters (Blood Urea Nitrogen, Cholesterol, Glucose, Phosphate, Potassium, Sodium and Urate) at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in chemistry parameters blood urea nitrogen, cholesterol, glucose, phosphate, potassium, sodium and urate were studies. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Chemistry Parameters (Bilirubin and Creatinine) at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in chemistry parameters bilirubin and creatinine were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Thyrotropin at Early Termination/ Day 360 Baseline, Early termination/Day 360 Change from baseline in thyrotropin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Thyroxine,Free at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in thyroxine,free were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Urinalysis (Specific Gravity) at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in urine specific gravity were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Hematocrit at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter hematocrit were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Hemoglobin at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter hemoglobin were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Hematology Parameters (Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume) at Early Termination/ Day 360 Baseline, Early termination/Day 360 Change from baseline in hematology parameter erythrocytes mean corpuscular volume and mean platelet volume were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Chemistry Parameters at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in chemistry parameter alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, and lactate dehydrogenase were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Urobilinogen at Early Termination/Day 360 Baseline, Early termination/Day 360 Change from baseline in urobilinogen were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Urine Potential of Hydrogen (pH) at Early Termination/Day 360 Baseline, Early Termination/Day 360 Change from baseline in urine pH were reported. Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Change From Baseline in Heart Rate at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Heart rate was measured by Electrocardiogram (ECG). ECG was performed using the central ECG provider's equipment and was send to the central ECG provider electronically. Change from baseline in heart rate at FoTA were reported. FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product.
Change From Baseline in Electrocardiogram Parameters at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) ECG was performed using the central ECG provider's equipment and was sent to the central ECG provider electronically to measure PR, RR, QRS , QT, QTcB and QTcF intervals. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date).Group A baseline was the baseline of the antecedent studies. Group B baseline was the average of all valid ECG measurements as the last assessment obtained before the first dose of investigational product.
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) FoTA (up to 330 days) PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. The assessment was done by the nature of the responses, not by a numbered scale. Participants analyzed for number of times woke up per night category were only the participants who responded as yes for the woke up during the night category in this outcome measure. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product.
Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) FoTA (up to 330 days) PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time awake per night and length of time to fall asleep per night was assessed at FoTA.
Length of Time Sleeping Per Night Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment (FoTA) FoTA (up to 330 days) PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collects data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date). Group A baseline was the baseline of the antecedent studies. Group B baseline was the last value collected before the first dose of investigational product. Length of time sleeping per night was assessed at FoTA.
Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment (FoTA) FoTA (up to 330 days) CSHQ was a tool designed to screen for the most common sleep problems in children and consisted of 33 items for scoring and several extra items intended to provide administrators with other potentially useful information about respondents. The instrument evaluates the 8 different subscales: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. A 3-point scale was used for rating: "usually" if the sleep behavior occurs 5 to 7 times per week, "sometimes" for 2 to 4 times per week, and "rarely" for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.
Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 330 Day 330 C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The number of participants with postive response in suicidal ideation and suicidal behavior were reported.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Clinician-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Final On-Treatment Assessment (FoTA) Baseline, FoTA (up to 330 days) Clinician administered ADHD-RS-5, child, home version total score were analyzed. ADHD-RS-5 consists of 18 items designed to reflect current symptomatology of ADHD based on diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items may be grouped into 2 subscales: hyperactivity/impulsivity (9 items) and inattentiveness (9 items). Higher total scores indicated higher impairment and lower scores indicated no impairment. FoTA was defined as the last valid assessment obtained after Baseline and whilst on investigational product (on or before 2 days after the last dose date).
Clinical Global Impression of Improvement (CGI-I) at Final On-Treatment Assessment (FoTA) FoTA (up to 330 days) CGI-I scale was performed to rate the improvement of a participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). FoTA was defined as the last valid assessment obtained after baseline and whilst on investigational product (on or before 2 days after the last dose date).
Trial Locations
- Locations (45)
PEWMD, PA, ARCSM, PLLC, PRP, Inc.
🇺🇸Little Rock, Arkansas, United States
Neuroscientific Insights
🇺🇸Rockville, Maryland, United States
Neurobehavioral Medicine Group
🇺🇸Bloomfield Hills, Michigan, United States
Alivation Research, LLC.
🇺🇸Lincoln, Nebraska, United States
Advanced Research Center
🇺🇸Anaheim, California, United States
Riverside Medical Clinic
🇺🇸Riverside, California, United States
One Health Research Clinic, Inc.
🇺🇸Norcross, Georgia, United States
Psychiatric Associates
🇺🇸Overland Park, Kansas, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Acevedo Medical Group
🇺🇸Miami, Florida, United States
Pharmacology Research, LLC
🇺🇸Miami, Florida, United States
Harmonex Neuroscience Research
🇺🇸Dothan, Alabama, United States
Power MD Clinical Research Institute
🇺🇸Hialeah, Florida, United States
Buford Family Practice
🇺🇸Buford, Georgia, United States
Advanced Clinical Research, Inc
🇺🇸Meridian, Idaho, United States
Conventions Psychiatry and Counseling
🇺🇸Naperville, Illinois, United States
Kentucky Pediatric/Adult Research
🇺🇸Bardstown, Kentucky, United States
Qualmedica Research LLC, DBA Pedia Research
🇺🇸Owensboro, Kentucky, United States
St Charles Psychiatric Associates
🇺🇸Saint Charles, Missouri, United States
Professional Psychiatric Services
🇺🇸Mason, Ohio, United States
Rainbow Research, Inc.
🇺🇸Barnwell, South Carolina, United States
Ohio Pediatric Research Association
🇺🇸Dayton, Ohio, United States
Family Practice Center of Wadsworth, INC.
🇺🇸Wadsworth, Ohio, United States
Coastal Pediatric Associates
🇺🇸Mount Pleasant, South Carolina, United States
Houston Clinical Trials, LLC
🇺🇸Houston, Texas, United States
El Campo Clinical Trials
🇺🇸El Campo, Texas, United States
Children's Clinic
🇺🇸League City, Texas, United States
VA South Psychiatric & Family Services
🇺🇸Petersburg, Virginia, United States
Family Psychiatry of the Woodlands
🇺🇸The Woodlands, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Mid-Columbia Research
🇺🇸Richland, Washington, United States
Northwest Clinical Research Center
🇺🇸Bellevue, Washington, United States
Care Research Center
🇺🇸Doral, Florida, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Memphis, Tennessee, United States
Scientific Clinical Research, Inc.
🇺🇸North Miami, Florida, United States
GA Psychiatric Services, LLC.
🇺🇸Atlanta, Georgia, United States
Peninsula Research Associates - CRN
🇺🇸Rolling Hills, California, United States
Institute for Behavioral Medicine
🇺🇸Smyrna, Georgia, United States
Pediatric Medical Associates
🇺🇸Sacramento, California, United States
Clinical Associates of Orlando, Llc
🇺🇸Orlando, Florida, United States
Triangle Neuropsychiatry
🇺🇸Durham, North Carolina, United States
IPS Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Access Clinical Trials, Inc.
🇺🇸Nashville, Tennessee, United States
University of Texas
🇺🇸San Antonio, Texas, United States
Pedia Research, LLC
🇺🇸Evansville, Indiana, United States