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SHP465

Phase 3

Attention Deficit Hyperactivity Disorder (ADHD) | Small molecule | Psychiatry |Takeda Pharmaceutical Company Limited|Trials Updated: Jun 8, 2021

SHP465 development status

Highest phase Phase 3
Registered trials 4 across 1 sponsor since Jun 2015

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials5
Total Enrollment679

FDA Designations

No designations recorded

SHP465 clinical trials

SHP465 · 5 trials · 1 indication

Phase 3 3Phase 1 2
NCT03325881Efficacy and Safety of SHP465 at 6.25 mg in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-12 YearsAttention Deficit Hyperactivity Disorder (ADHD)
COMPLETED89 Analytics
NCT02604407Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)Attention Deficit Hyperactivity Disorder (ADHD)
COMPLETED275 Analytics
NCT02466425Safety and Efficacy Study of SHP465 in Children and Adolescents Aged 6-17 Years With Attention-Deficit Hyperactivity Disorder (ADHD)Attention Deficit Hyperactivity Disorder (ADHD)
COMPLETED264 Analytics
PHASE3COMPLETED
Efficacy and Safety of SHP465 at 6.25 mg in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-12 Years
Attention Deficit Hyperactivity Disorder (ADHD)Unlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)
Attention Deficit Hyperactivity Disorder (ADHD)Unlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study of SHP465 in Children and Adolescents Aged 6-17 Years With Attention-Deficit Hyperactivity Disorder (ADHD)
Attention Deficit Hyperactivity Disorder (ADHD)Unlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Week 4
Baseline, Week 4

Clinician administered ADHD-RS-5, child, home version total score were analyzed. ADHD-RS-5 consisted 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 was 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 were grouped into 2 subscales: hyperactivity or impulsivity (9 items) and inattentiveness (9 items). Higher total scores indicated higher impairment and lower scores indicated no impairment. Least square (LS) mean was calculated based on restricted maximum likelihood (REML) method of estimation and utilized an unstructured covariance type.

Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4)
Baseline, Visit 6 (Week 4)

The ADHD-RS was developed to measure the behaviors of children with Attention deficit hyperactivity disorder (ADHD). The adult ADHD-RS with prompts consists of 18 items designated to reflect current symptomatology of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher score = more severe symptoms.The scale is subdivided into 2 subscales of 9 symptoms each: hyperactivity/impulsivity and inattentiveness. Adult prompts are included with the ADHD-RS to create a semistructured measurement that allows the clinician to probe the extent, frequency, breadth, severity, and consequences of these symptoms to ascertain impairment in an adult population.

Change From Baseline in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score at Visit 6 (Week 4)
Baseline, Visit 6 (Week 4)

The ADHD-RS-IV consists of 18 items designed to reflect current symptomatology of ADHD based on diagnostic and statistical manual of mental disorders, fourth edition - text revision (DSM-IV-TR) 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 (even-numbered items 2-18) and inattentiveness (odd-numbered items 1-17). Higher score = more severe symptoms.

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)
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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).

Maximum Observed Drug Concentration (Cmax) of Dextroamphetamine (d-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Maximum concentration occurring at time of maximum observed concentration of d-amphetamine during a dosing interval.

Maximum Observed Drug Concentration (Cmax) for Levoamphetamine (l-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Maximum observed concentration of l-amphetamine during a dosing interval.

Time to Reach Maximum Observed Drug Concentration (Tmax) of Dextroamphetamine (d-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Time to reach maximum observed drug concentration of d-amphetamine during a dosing interval.

Time to Reach Maximum Observed Drug Concentration (Tmax) of Levoamphetamine (l-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Time to reach maximum observed drug concentration of l-amphetamine during a dosing interval.

Area Under the Curve From Zero to Infinity (AUC0-infinity) of Dextroamphetamine (d-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

AUC0-infinity was calculated using the observed value of the last non-zero concentration of d-amphetamine in plasma.

Area Under the Curve From Zero to Infinity (AUC0-infinity) of Levoamphetamine (l-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

AUC0-infinity was calculated using the observed value of the last non-zero concentration of l-amphetamine in plasma.

Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Dextroamphetamine (d-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Area under the curve from the time of dosing to the last measurable concentration of d-amphetamine in plasma.

Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Levoamphetamine (l-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Area under the curve from the time of dosing to the last measurable concentration of l-amphetamine in plasma.

Terminal Half-life (t½) of Dextramphetamine (d-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Terminal half-life is the time measured for the plasma concentration of d-amphetamine to decrease by one half.

Terminal Half-life (t½) of Levoamphetamine (l-amphetamine) in Plasma
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Terminal half-life is the time measured for the plasma concentration of l-amphetamine to decrease by one half.

Total Body Clearance for Extravascular Administration (CL/F) of Dextroamphetamine (d-amphetamine)
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Total body clearance for extravascular administration of d-amphetamine divided by the fraction of dose absorbed.

Total Body Clearance for Extravascular Administration (CL/F) of Levoamphetamine (l-amphetamine)
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Total body clearance for extravascular administration of l-amphetamine divided by the fraction of dose absorbed.

Volume of Distribution After Extravascular Administration (Vz/F) of Dextroamphetamine (d-amphetamine)
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Volume of distribution for d-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed.

Volume of Distribution After Extravascular Administration (Vz/F) of Levoamphetamine (l-amphetamine)
Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose

Volume of distribution for l-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed.

Secondary Endpoints

Clinical Global Impression of Improvement (CGI-I) at Week 4
Week 4
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
From start of study drug administration up to follow-up (Week 5)
Number of Participants With Clinically Significant Change in Vital Signs Were Reported as Adverse Event (AE)
From start of study drug administration up to follow-up (Week 5)
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
SHP465EXPERIMENTALParticipants will be randomized to receive SHP465 capsule 6.25 milligram (mg) orally once daily for 4 weeks.
PlaceboPLACEBO_COMPARATORParticipant will receive placebo matching to SHP465 capsule orally once daily for 4 weeks.
SHP465 12.5 mgEXPERIMENTALSubjects will receive SHP465 12.5 mg
SHP465 37.5 mgEXPERIMENTALSubjects will receive SHP465 titrated up to 37.5 mg
SHP465 25 mgEXPERIMENTALA single dose of SHP465 25 mg for Subjects aged 13-17 years

Interventions

NameTypeDescription
SHP465DRUGSHP465 capsule 6.25 mg orally once daily for 4 weeks
PlaceboDRUGPlacebo matching to SHP465 capsule orally once daily for 4 weeks
SHP465 12.5mg capsules (one capsule daily)DRUGone capsule daily
SHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily)DRUGOne capsule daily
SHP465 12.5mgDRUG -
SHP465 25mgDRUG -
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Eligibility Criteria

Age Range6 Years to 12 Years
SexALL
Healthy VolunteersNo
Study Sites41

Inclusion Criteria: * Participant is male or female aged 6-12 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. * Partici...

Countries:United States
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Frequently asked questions about SHP465

What is SHP465 used for?

SHP465 is being developed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). It is a small molecule therapeutic candidate studied in children, adolescents, and adults with ADHD. Takeda Pharmaceutical Company Limited is developing the asset, which has completed five clinical trials in this indication.

Who is developing SHP465?

SHP465 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company has sponsored five completed clinical trials of SHP465 in ADHD, including Phase 1 and Phase 3 studies conducted in the United States.

What phase is SHP465 in?

SHP465 has completed Phase 3 clinical development for ADHD. Five trials have been completed, including Phase 3 efficacy and safety studies in children aged 6 to 12 years and in adults aged 18 to 55 years, as well as Phase 1 pharmacokinetic and safety studies.

What clinical trials is SHP465 in?

SHP465 has been studied in five completed trials, including NCT03327402, a Phase 1 safety and pharmacokinetic study in children aged 4 to 5 years; NCT03325881, a Phase 3 efficacy and safety trial in children aged 6 to 12 years; NCT02604407, a Phase 3 study in adults aged 18 to 55 years; and NCT02578030, a Phase 1 pharmacokinetic study in children and adolescents aged 6 to 17 years.