Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Extended-release Guanfacine Hydrochloride; Atomoxetine Hydrochloride; Placebo Comparator
Intervention description: Tablet, once daily, optimised dose (1mg to 7mg based on age and weight), 6-week maintenance duration on optimised dose.; Capsule, once daily, optimised dose (10mg to 100mg based on weight), 8-9-weeks maintenance duration on optimised dose; Placebo
Intervention MeSH terms: Guanfacine; Atomoxetine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 338.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: ADHD

Summary:

      For children and adolescents, how does SPD503 compare to placebo for the treatment of
      Attention-Deficit/Hyperactivity Disorder (ADHD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, aged 6 17 years at the time of consent/assent at Screening (Visit 1).

          2. Subject's parent or legally authorised representative (LAR) must provide signature of
             informed consent, and there must be documentation of assent (if applicable) by the
             subject indicating that the subject is aware of the investigational nature of the
             study and the required procedures and restrictions in accordance with the
             International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidance
             E6, and applicable regulations before completing any study related procedures at
             Screening (Visit 1).

          3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text
             Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, combined sub-type,
             hyperactive/impulsive sub-type, or inattentive sub-type based on a detailed
             psychiatric evaluation using the Kiddie Schedule for Affective Disorders and
             Schizophrenia - Present and Lifetime version (K-SADS-PL).

          4. Subject has a minimum ADHD-RS-IV total score of 32 at Baseline (Visit 2).

          5. Subject has a minimum CGI-S score of 4 at Baseline (Visit 2).

          6. Subject is functioning at an age-appropriate level intellectually, as judged by the
             Investigator.

          7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with
             the study procedures and restrictions defined in this protocol.

          8. Subject is able to swallow intact tablets and capsules.

          9. Subject who is a female of child-bearing potential (FOCP), defined as greater than or
             equal to 9 years of age or <9 years of age and is menarchal, must have a negative
             serum beta Human Chorionic Gonadotropin (hCG) pregnancy test at Screening (Visit 1)
             and a negative urine pregnancy test at Baseline (Visit 2) and agree to comply with any
             applicable contraceptive requirements of the protocol.

         10. Subject has supine and standing blood pressure (BP) measurement within the 95th
             percentile for age, sex, and height

        Exclusion Criteria:

          1. Subject has a current, controlled (requiring a prohibited medication or behavioural
             modification program) or uncontrolled, co-morbid psychiatric diagnosis [except
             oppositional defiant disorder (ODD)], including any severe co-morbid Axis II disorders
             or severe Axis I disorders such as post traumatic stress disorder (PTSD), bipolar
             illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder
             (OCD), substance abuse disorder, or other symptomatic manifestations or lifetime
             history of bipolar illness, psychosis or conduct disorder that, in the opinion of the
             Investigator, contraindicate treatment with SPD503 or STRATTERA or confound efficacy
             or safety assessments.

          2. Subject is well-controlled on their current medication, with acceptable tolerability,
             and the parent/caregiver does not object to the current medication.

          3. Subject has any condition or illness including a clinically significant abnormal
             Screening (Visit 1) laboratory values which, in the opinion of the Investigator,
             represents an inappropriate risk to the subject and/or could confound the
             interpretation of the study. Mild stable asthma treated without the use of beta-2
             agonist is not exclusionary.

          4. Subject has a known history or presence of structural cardiac abnormalities,
             cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities,
             syncope, tachycardia, cardiac conduction problems (eg, clinically significant heart
             block or QT interval prolongation), exercise-related cardiac events including syncope
             and pre syncope, or clinically significant bradycardia.

          5. Subject has a known family history of sudden cardiac death, ventricular arrhythmia, or
             QT prolongation.

          6. Subjects with orthostatic hypotension or a known history of hypertension.

          7. Subject has glaucoma.

          8. Subject has clinically significant ECG findings as judged by the Investigator with
             consideration of the central ECG laboratory's interpretation.

          9. Subject has a history of a seizure disorder (other than a single childhood febrile
             seizure occurring before the age of 3 years) or the presence of a serious tic disorder
             including Tourette's Syndrome.

         10. Current use of any prohibited medication or other medications, including monoamine
             oxidase inhibitors, herbal supplements, that affect BP or heart rate potent CYP2D6
             inhibitors, medications known to prolong the QT/QTc interval, medications that lower
             seizure threshold, pressor agents, beta-2 agonists, medications that affect
             noradrenaline, medications that have central nervous system (CNS) effects or affect
             cognitive performance, such as sedating antihistamines and decongestant
             sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use
             of sedating medications [ie, antihistamines]) in violation of the protocol specified
             washout criteria at Baseline (Visit 2).

         11. Subject has a history of alcohol or other substance abuse or dependence, as defined by
             DSM-IV (with the exception of nicotine) within the last 6 months.

         12. Subject has taken another investigational product within 30 days prior to Baseline
             (Visit 2).

         13. Subject is significantly overweight based on Center for Disease Control and Prevention
             Body Mass Index (BMI)-for-age gender specific charts at the Screening (Visit 1).
             Significantly overweight is defined as a BMI >95th percentile.

         14. Children aged 6 12 years with a body weight of less than 25kg or adolescents aged 13
             17 years with a body weight of less than 34kg or greater than 91kg at Screening (Visit
             1).

         15. Subject has a known or suspected allergy, hypersensitivity, or clinically significant
             intolerance to guanfacine hydrochloride or atomoxetine hydrochloride, or any
             components found in SPD503 or STRATTERA.

         16. Clinically important abnormality on drug and alcohol screen (excluding the subject's
             current ADHD stimulant if applicable) at Screening (Visit 1)

         17. Subject is female and is pregnant or currently lactating.

         18. Subject failed screening or was previously enrolled in this study.

         19. Subject 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 is currently
             demonstrating active suicide ideation. Subjects with intermittent passive suicidal
             ideation are not necessarily excluded based on the assessment of the Investigator.

         20. History of failure to respond to an adequate trial of an α2-agonist or atomoxetine
             hydrochloride for the treatment of ADHD (consisting of an appropriate dose and
             adequate duration of therapy in the opinion of the investigator).

         21. Subjects with renal or hepatic insufficiency.