Attention Deficit Hyperactivity Disorder (ADHD)Phase 1NCT03327402
Safety, Tolerability and Pharmacokinetics of SHP465 in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)
A Phase 1 study testing SHP465 in people with Attention Deficit Hyperactivity Disorder (ADHD), run by Shire at 8 sites in United States.
Trial summary
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of SHP465 in children aged 4 to 5 years with ADHD after multiple daily doses of 6.25 milligram (mg) SHP465 Read more about this study
- Who is it for?
- Ages 4 to 5 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder (ADHD)
- What is being tested?
- SHP465
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 8 sitesUnited States
- Study dates
- 13 Mar 2018to 5 Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female aged 4-5 years inclusive at the time of consent with a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and has undergone nonpharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior nonpharmacological treatment, based on the investigator's judgment or has never taken ADHD medication or has taken ADHD medication with unacceptable efficacy and/or tolerability.
- Participant's parent/legally authorized representative (LAR) must sign the informed consent form, and there must be documentation of assent (if applicable) and is willing and able to fully comply with all of the testing and requirements defined in the protocol.
- Participant during the screening period:
- Has a total score of ADHD-RS-5 >=28 for boys and >=24 for girls. ii. Has a Clinical Global Impressions-Severity of Illness (CGI-S) score >=4. iii.Functions at an age-appropriate level intellectually, as determined by the investigator.
- Participant has the ability to take investigational product by either swallowing the capsule whole or sprinkling the capsule contents in applesauce and ingesting the entire mixture immediately without chewing.
- Participant has lived with the same parent/LAR for at least 6 months.
Who cannot join
- Prior enrollment or participation in the study.
- Documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
- Participant cannot swallow a pill and/or applesauce, or has an allergy to applesauce.
- Participant is currently taking or has taken ADHD medication with acceptable efficacy and tolerability.
- Participant has taken ADHD medication within 7 days prior to the administration of investigational product.
- Participant has used any medication (including over-the-counter, herbal, or homeopathic preparations) within 30 days prior to the administration of investigational product or 5 half-lives, whichever is longer, with the exception of the following:
Show all 25Show fewer
- Thyroid medication ii. Intermittent use of nonsteroidal anti-inflammatory drugs or acetaminophen iii. As needed use of a beta-agonists inhaler for mild asthma or exercise induced bronchospasm iv. Over-the-counter nonsedating antihistamines for allergies. v. Participant has continuously used oral corticosteroids >=7 days in 3 months prior to investigational product dosing. If continuous use was less than (<) 7 days, 1 month of washout prior to dosing of investigational product is required.
- Within 30 days prior to the administration of investigational product (IP):
- Participant has used an IP.
- If the elimination half-life of the previous study's IP was less than 6 days, then the last dose of the previous IP should be 30 days prior to the first dose of SHP465.
- If the elimination half-life of the previous study's IP was greater than 6 days, then the last dose of the previous IP should be 5 half-lives prior to the dose of SHP465.
- Glaucoma.
- Known family history of sudden cardiac death or ventricular arrhythmia.
- 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.
- Any clinically significant ECG or clinically significant laboratory abnormalities at the first screening visit based on the investigator's judgment. A single retest of laboratory parameters is allowed based on the investigator's judgment.
- Marfan's syndrome.
- Blood pressure >= 95th percentile for age, sex, and height at the screening visit.
- Height and weight <= 5th percentile for age and sex at the first screening visit.
- Current abnormal thyroid function test results, defined as abnormal thyroid-stimulating hormone, thyroxine (T4), and tri-iodothyronine (T3) at the first screening visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
- History of seizures (other than infantile febrile seizures).
- Current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder including but not limited to any of the following comorbid Axis I disorders and Axis II disorders.
- Currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or is currently demonstrating active suicidal ideation.
- History of physical, sexual, or emotional abuse.
- Primary sleep disorder (eg, sleep apnea, narcolepsy).
- Eating disorder.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio Pediatric Research Assn Inc
Dayton, Ohio, 45414
Qualmedica Research, LLC
Evansville, Indiana, 47715
Preferred Research Partners
Little Rock, Arkansas, 72211
Professional Psychiatric Services (PPS)
Mason, Ohio, 45040
Clinical Neuroscience Solutions Inc
Memphis, Tennessee, 38119
Coastal Pediatric Associates
Mt. Pleasant, South Carolina, 29464
Clinical Neuroscience Solutions Inc
Orlando, Florida, 32801
About this study
Official title: A Phase 1 Open-label Study of the Safety, Tolerability, and Pharmacokinetics of d- and l-Amphetamine After Multiple Daily Doses of SHP465 6.25 mg Administered in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of SHP465 in children aged 4 to 5 years with ADHD after multiple daily doses of 6.25 milligram (mg) SHP465
- Being tested
- SHP465
- Keywords
- SHP465, ADHD, Hyperactivity
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Spasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHP465Drug
SHP465 capsule will be administered at a dose of 6.25 mg, orally once daily for 4 weeks. SHP465 is comprised of sulfate salts of dextroamphetamine and amphetamine, with dextroamphetamine saccharate and amphetamine aspartate monohydrate, which provide a composite enantiomer ratio of 3:1 d-amphetamine to l-amphetamine.
| Study group | Role | What they receive |
|---|---|---|
| SHP465 | Experimental | Participants will receive SHP465 capsule at a dose of 6.25 mg, orally once daily for 4 weeks. Receives: Drug: SHP465 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Drug Concentration (Cmax) Occurred at the Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Plasma Dextroamphetamine (d-Amphetamine) and Plasma Levoamphetamine (l-Amphetamine)
Maximum plasma drug concentration occurred at time of maximum observed concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Trough Plasma Drug Concentration Ctrough at Steady State (Ctrough,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Trough plasma drug concentration (predose concentrations collected at steady state) of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Predose on Day 1 and Day 28 and at 24 hours (Day 29) postdose on Day 28
Time to Reach Maximum Observed Plasma Drug Concentration (Tmax) During Dosing Interval of Plasma d-Amphetamine and Plasma l-Amphetamine
Time to reach maximum observed plasma drug concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area Under the Concentration-Time Curve From Time Zero to the Last Timepoint (AUC0-t) During Sample Collection of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve from time zero to the last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area Under the Concentration-Time Curve From Time Zero Predose to Five Hours Postdose (AUC0-5) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration time curve from time zero predose to five hours postdose of plasma d-amphetamine and plasma d-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5 hours Postdose on Day 7
Area Under the Concentration Time Curve From Time Five Hours to the Last Timepoint (AUC5-t) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration time curve from time five hours to the time of last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area Under the Concentration-Time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve from time of dosing to the last measurable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area Under the Concentration-Time Curve Over the Dosing Interval (24 Hours) at Steady State (AUCtau,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve over the dosing interval (24 hours) at steady state of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Terminal Rate Constant (Lambda z) of Plasma d-Amphetamine and Plasma l-Amphetamine
Terminal Rate Constant of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Total Body Clearance (CL/F) for Extravascular Administration of Plasma d-Amphetamine and Plasma l-Amphetamine
Apparent total clearance of the plasma drug concentration of plasma d- amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Terminal Half-life (t1/2) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time required for the plasma drug concentration to reach half of its original value of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Apparent Volume of Distribution (Vss/F) at Steady State of Plasma d-Amphetamine and Plasma l-Amphetamine
Apparent volume of distribution at steady state of plasma d-amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had 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 (IP) and no later than 3 days following the last dose of IP.
Measured: From start of study drug administration up to follow-up (up to 5 weeks)
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE.
Measured: From start of study drug administration up to follow-up (up to 5 weeks)
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.
Measured: From start of study drug administration up to follow-up (up to 5 weeks)
Change From Baseline in Height at Final On-Treatment Assessment
Height (in centimeters) was measured using a stadiometer with the participant standing on a flat surface without shoes and with the chin parallel to the floor. Final on-treatment assessment (FoTA) was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Change From Baseline in Weight at Final On-Treatment Assessment
Weight (in kilograms) was measured using a calibrated scale. Participant should be in light clothes and without shoes. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
Clinical laboratory tests included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE.
Measured: From start of study drug administration up to follow-up (up to 5 weeks)
Number of Participants With Overall Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Length of Time Awake Per Night Assessed by PSQ at Final On-Treatment Assessment
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Length of Time to Fall Asleep Per Night Assessed by PSQ at Final On-Treatment Assessment
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Length of Time Sleeping Per Night Assessed by PSQ at Final On-Treatment Assessment
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment
The CSHQ was a validated, retrospective, parent-reported sleep screening tool. The questionnaire consisted of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. Each item receives a score from 1 (meaning the problem occurs rarely) to 3 (meaning the problem usually occurs); therefore, a higher score is the worse outcome. Scale ranges are as follows: Bedtime Resistance: 6 to 18, Sleep Onset Delay: 1 to 3, Sleep Duration: 3 to 9, Sleep Anxiety: 4 to 12, Night Wakings: 3 to 9, Parasomnias: 7 to 21, Disordered Breathing: 3 to 9, Daytime Sleepiness: 8 to 24, and Total Disturbance (items from all scales): 33 to 99. A negative value indicated less sleep disturbance.
Measured: FoTA (up to Day 30)
Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Final On-Treatment Assessment
C-SSRS was a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts (suicidal ideation) and suicidal behaviors during the assessment period needed to be determine if a suicide-related thought or behavior were occurred. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Measured: FoTA (up to Day 30)
Secondary outcomes (6)
Observed Analyte Concentration at 12 Hours After Dose Administration (C12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 12 hours after dose administration were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 12 hours (Day 8) Postdose on Day 7
Observed Analyte Concentration at 16 Hours After Dose Administration (C16) of Plasma d-Amphetamine and Plasma l- Amphetamine
Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 16 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 16 hours (Day 8) Postdose on Day 7
Observed Analyte Concentration at 24 Hours After Dose Administration (C24) of Plasma d-Amphetamine and Plasma l- Amphetamine
Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 24 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 24 hours (Day 8) Postdose on Day 7
Area Under the Concentration-Time Curve From Time Five Hours to Twelve Hours Postdose (AUC5-12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve from time five hours to twelve hours postdose (AUC5-12) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 5, 8, 12 hours Postdose on Day 7
Area Under the Concentration-Time Curve From Time Twelve Hours to Sixteen Hours Postdose (AUC12-16) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve from time twelve hours to sixteen hours postdose (AUC12-16) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 12, 16 hours Postdose on Day 7
Area Under the Concentration-Time Curve From Time Sixteen Hours to Twenty-Four Hours Postdose (AUC16-24) of Plasma d-Amphetamine and Plasma l-Amphetamine
Area under the concentration-time curve from time sixteen hours to twenty-four hours postdose (AUC16-24) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Measured: Week 4: 16, 24 hours (Day 8) Postdose on Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start13 Mar 2018
- Primary completion5 Oct 2018
- Study completion5 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity Disorder (ADHD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03327402
- Sponsor's protocol ID
- SHP465-112
- Status last verified
- May 2021
- First submitted
- 27 Oct 2017
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Ilic K, Kugler AR, Yan B, McNamara N. Pharmacokinetics, Safety, and Tolerability of SHP465 Mixed Amphetamine Salts After Administration of Multiple Daily Doses in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2022 Jan;36(1):71-81. doi: 10.1007/s40263-021-00870-5. Epub 2021 Nov 26.
PubMed 34826114
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label Study of the Safety, Tolerability, and Pharmacokinetics of d- and l-Amphetamine After Multiple Daily Doses of SHP465 6.25 mg Administered in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT03327402
- Acronym / sponsor ID
- SHP465-112
- Keywords
- SHP465, ADHD, Hyperactivity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2018 (actual)
- Primary completion
- 5 Oct 2018 (actual)
- Study completion
- 5 Oct 2018 (actual)
- First posted
- 31 Oct 2017 (actual)
- Results
- Posted 29 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of SHP465 in children aged 4 to 5 years with ADHD after multiple daily doses of 6.25 milligram (mg) SHP465
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SHP465 | Experimental | Drug: SHP465Participants will receive SHP465 capsule at a dose of 6.25 mg, orally once daily for 4 weeks. |
Who may qualify
- Ages
- 4 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male or female aged 4-5 years inclusive at the time of consent with a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and has undergone nonpharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior nonpharmacological treatment, based on the investigator's judgment or has never taken ADHD medication or has taken ADHD medication with unacceptable efficacy and/or tolerability.
- Participant's parent/legally authorized representative (LAR) must sign the informed consent form, and there must be documentation of assent (if applicable) and is willing and able to fully comply with all of the testing and requirements defined in the protocol.
- Participant during the screening period:
- Participant has the ability to take investigational product by either swallowing the capsule whole or sprinkling the capsule contents in applesauce and ingesting the entire mixture immediately without chewing.
- Participant has lived with the same parent/LAR for at least 6 months.
Key exclusion criteria (25 listed)
- Prior enrollment or participation in the study.
- Documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
- Participant cannot swallow a pill and/or applesauce, or has an allergy to applesauce.
- Participant is currently taking or has taken ADHD medication with acceptable efficacy and tolerability.
- Participant has taken ADHD medication within 7 days prior to the administration of investigational product.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHP465SHP465 capsule will be administered at a dose of 6.25 mg, orally once daily for 4 weeks. SHP465 is comprised of sulfate salts of dextroamphetamine and amphetamine, with dextroamphetamine saccharate and amphetamine aspartate monohydrate, which provide a composite enantiomer ratio of 3:1 d-amphetamine to l-amphetamine. | Drug | SHP465 |
Primary outcome
Maximum Plasma Drug Concentration (Cmax) Occurred at the Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Plasma Dextroamphetamine (d-Amphetamine) and Plasma Levoamphetamine (l-Amphetamine)
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Maximum plasma drug concentration occurred at time of maximum observed concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Trough Plasma Drug Concentration Ctrough at Steady State (Ctrough,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Predose on Day 1 and Day 28 and at 24 hours (Day 29) postdose on Day 28
Trough plasma drug concentration (predose concentrations collected at steady state) of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time to Reach Maximum Observed Plasma Drug Concentration (Tmax) During Dosing Interval of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Time to reach maximum observed plasma drug concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Area Under the Concentration-Time Curve From Time Zero to the Last Timepoint (AUC0-t) During Sample Collection of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area under the concentration-time curve from time zero to the last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Area Under the Concentration-Time Curve From Time Zero Predose to Five Hours Postdose (AUC0-5) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5 hours Postdose on Day 7
Area under the concentration time curve from time zero predose to five hours postdose of plasma d-amphetamine and plasma d-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Area Under the Concentration Time Curve From Time Five Hours to the Last Timepoint (AUC5-t) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area under the concentration time curve from time five hours to the time of last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Area Under the Concentration-Time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area under the concentration-time curve from time of dosing to the last measurable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Area Under the Concentration-Time Curve Over the Dosing Interval (24 Hours) at Steady State (AUCtau,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Area under the concentration-time curve over the dosing interval (24 hours) at steady state of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Terminal Rate Constant (Lambda z) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Terminal Rate Constant of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Total Body Clearance (CL/F) for Extravascular Administration of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Apparent total clearance of the plasma drug concentration of plasma d- amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Terminal Half-life (t1/2) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Time required for the plasma drug concentration to reach half of its original value of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Apparent Volume of Distribution (Vss/F) at Steady State of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7
Apparent volume of distribution at steady state of plasma d-amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (up to 5 weeks)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had 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 (IP) and no later than 3 days following the last dose of IP.
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Time frame: From start of study drug administration up to follow-up (up to 5 weeks)
Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
Time frame: From start of study drug administration up to follow-up (up to 5 weeks)
12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.
Change From Baseline in Height at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
Height (in centimeters) was measured using a stadiometer with the participant standing on a flat surface without shoes and with the chin parallel to the floor. Final on-treatment assessment (FoTA) was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Change From Baseline in Weight at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
Weight (in kilograms) was measured using a calibrated scale. Participant should be in light clothes and without shoes. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
Time frame: From start of study drug administration up to follow-up (up to 5 weeks)
Clinical laboratory tests included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE.
Number of Participants With Overall Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Length of Time Awake Per Night Assessed by PSQ at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Length of Time to Fall Asleep Per Night Assessed by PSQ at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Length of Time Sleeping Per Night Assessed by PSQ at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected 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 while on IP (on or before 2 days after the last dose date).
Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
The CSHQ was a validated, retrospective, parent-reported sleep screening tool. The questionnaire consisted of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. Each item receives a score from 1 (meaning the problem occurs rarely) to 3 (meaning the problem usually occurs); therefore, a higher score is the worse outcome. Scale ranges are as follows: Bedtime Resistance: 6 to 18, Sleep Onset Delay: 1 to 3, Sleep Duration: 3 to 9, Sleep Anxiety: 4 to 12, Night Wakings: 3 to 9, Parasomnias: 7 to 21, Disordered Breathing: 3 to 9, Daytime Sleepiness: 8 to 24, and Total Disturbance (items from all scales): 33 to 99. A negative value indicated less sleep disturbance.
Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Final On-Treatment Assessment
Time frame: FoTA (up to Day 30)
C-SSRS was a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts (suicidal ideation) and suicidal behaviors during the assessment period needed to be determine if a suicide-related thought or behavior were occurred. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
6 secondary outcomes
Observed Analyte Concentration at 12 Hours After Dose Administration (C12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: 12 hours (Day 8) Postdose on Day 7
Observed Analyte Concentration at 16 Hours After Dose Administration (C16) of Plasma d-Amphetamine and Plasma l- Amphetamine
Time frame: Week 4: 16 hours (Day 8) Postdose on Day 7
Observed Analyte Concentration at 24 Hours After Dose Administration (C24) of Plasma d-Amphetamine and Plasma l- Amphetamine
Time frame: Week 4: 24 hours (Day 8) Postdose on Day 7
Area Under the Concentration-Time Curve From Time Five Hours to Twelve Hours Postdose (AUC5-12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: 5, 8, 12 hours Postdose on Day 7
Area Under the Concentration-Time Curve From Time Twelve Hours to Sixteen Hours Postdose (AUC12-16) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: 12, 16 hours Postdose on Day 7
Area Under the Concentration-Time Curve From Time Sixteen Hours to Twenty-Four Hours Postdose (AUC16-24) of Plasma d-Amphetamine and Plasma l-Amphetamine
Time frame: Week 4: 16, 24 hours (Day 8) Postdose on Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34826114Ilic K, Kugler AR, Yan B, McNamara N. Pharmacokinetics, Safety, and Tolerability of SHP465 Mixed Amphetamine Salts After Administration of Multiple Daily Doses in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2022 Jan;36(1):71-81. doi: 10.1007/s40263-021-00870-5. Epub 2021 Nov 26.
- Individual participant dataSharing planned: 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.
Related trials for Attention Deficit Hyperactivity Disorder (ADHD)
Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
ADHD
Not yet recruitingPhase 2
Lisdexamfetamine For the Treatment of Conduct Disorder in Children
Conduct Disorder
RecruitingObservational study
Augmenting Parent Management Training for Child Temper Outbursts Using a Digital Tool
Disruptive Behavior Disorders, Conduct Disorder
Recruiting
Micronutrient Supplementation and Chronotherapy in Children With ADHD
Attention Deficit Hyperactivity Disorder (ADHD)
RecruitingPhase 3
Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol (FOCUS-2)
ADHD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SHP465 in people with Attention Deficit Hyperactivity Disorder (ADHD), run by Shire at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Plasma Drug Concentration (Cmax) Occurred at the Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Plasma Dextroamphetamine (d-Amphetamine) and Plasma Levoamphetamine (l-Amphetamine) (time frame: Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03327402, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.