guanfacine for hyperactivity in children with down syndrome (hypebegone_ds)

Conditions: Hyperactivity in Children With Down Syndrome; Impulsivity in Children With Down Syndrome

Summary: the purpose of this study is to determine efficacy of guanfacine immediate release (gir) for the treatment of hyperactivity/impulsivity and inattention in children 6-12 years of age with down syndrome (ds) after 8 weeks of treatment.

this is a randomized, double-blind, placebo-controlled flexibly dosed trial of guanfacine immediate release (gir) in children with down syndrome (ds) and symptoms of hyperactivity, inattention, and impulsivity. participants will undergo a screening period of up to 29 days. eligible participants meeting study criteria will be randomized 2:1 gir or placebo. there are a total of up to 4 in person visits (screening, baseline, at week 4, and at week 8). participants will receive gir or placebo for up to 8 weeks. weekly dose escalation will be determined via a telephone assessment at weeks 1-3 and weeks 4-7. unmasking of participant and site staff will occur at the week 8, in-person visit. after unmasking, participants who were randomized to receive gir will be given the option to 1) remain on gir and to transition to open-label gir per standard of care or 2) taper off of gir. a telephone safety assessment will be conducted for all participants, at 5 (+2) days after final study product administration. blood specimens will be collected at the week 4 and week 8 visits for pharmacokinetic (pk) analyses and lab assessments. participants will be asked to keep a daily study diary and will complete study measures at screening/baseline, week 4 and week 8. parents/caregivers will need to complete the study diary during the bridge/taper period for those who are in the gir arm.

Eligibility criteria:
inclusion: 1. parent/legal guardian can understand the consent process and is willing to provide informed consent/hipaa authorization prior to the conduct of any study-related procedures. when applicable, the minor participant is willing to provide assent. 2. participant has clinical diagnosis of non-mosaic ds. 3. participant is between 6 and 12 years of age (inclusive) at time of consent. 4. participant weight is ≥ 25 kg. 5. participant has clinically significant symptoms of hyperactivity, inattention and impulsivity manifested as minimum scores of the following rating scales within 30 days of randomization: 1. a minimum score of 18 on the parent-reported abc-h subscale, and 2. a minimum score of moderate or greater (≥ 4) on the clinician reported clinical global impression severity (cgi-s) score specific to hyperactivity, inattention and impulsivity behaviors. 6. participant has co-morbid medical screening and clearance to proceed with a non-stimulant medication trial with gir within 30 days of randomization. 7. participant is willing and able to comply with study procedures, including adherence to medication dosing schedule. exclusion: 1. participant has received guanfacine (any formulation) within 30 days of randomization. 2. participant has received any of the following concomitant medication classes within 30 days of randomization: 1. strong cyp3a4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole) 2. strong cyp3a4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and st. john's wort) 3. participant has a psychiatric comorbidity, such as major depressive disorder, bipolar disorder, obsessive-compulsive disorder, or a psychotic disorder, that requires a pharmacological treatment other than guanfacine 4. for participants ≥ 8 years old at the time of consent, participant has a history of suicidality or positive screen on ask suicide-screening questions (asq) tool. 5. participant is currently in or plans to participate in another interventional study. 6. participant has a known hypersensitivity to guanfacine. 7. participant has had a previous guanfacine treatment failure, as determined by their primary treating physician. 8. participant has had a change in another medication intended to treat symptoms of hyperactivity, inattention, and impulsivity within the last 2 weeks. 9. participant has had a seizure within the last 6 months. 10. participant has had a change in their anti-convulsant dose within the last 4 weeks. 11. participant has a cardiac-related condition including: 1. significant symptomatic bradycardia; 2. 2nd degree or 3rd degree (complete) heart block; 3. baseline heart rate (hr) or systolic blood pressure (bp) \> 2 standard deviations (sd) below mean for age as determined by medical examination; 4. history of aborted sudden cardiac death, unexplained syncope or near syncope, or historical use of a pacemaker as determined by medical history will require clearance by cardiology prior to enrollment; 5. known history of congenital heart disease which requires ongoing care for monitoring or management will require clearance by cardiology prior to enrollment. 12. participant has a history of untreated severe obstructive sleep apnea defined as obstructive apnea hypopnea index (oahi) ≥ 10 events per hour or aortic regurgitation (ar). participants with an oahi index \> 10/hr are eligible if managed with continuous positive airway pressure (cpap). 13. participant has untreated thyroid disease. 14. participant has a known hepatic impairment defined as aspartate aminotransferase (ast) or alanine aminotransferase (alt) \> 2x the upper limit of normal (uln) for age. 15. participant has known impending or renal failure defined as: 1. anuria diagnosed within 12 hours prior to enrollment; 2. requiring renal replacement therapy. 16. participant is pregnant. 17. participant has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study.

Keywords: hyperactivity impulsivity inattention