Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)

Overview

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.

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: November 2025

Detailed Description

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 drug diary and will complete study measures at screening/baseline, Week 4 and Week 8.

Interventions

• Drug: Guanfacine Hydrochloride Immediate Release
  • 0.5 mg capsules
• Drug: Placebo
  • Matching placebo capsule

Arms, Groups and Cohorts

• Active Comparator: Guanfacine Hydrochloride Immediate Release
  • Eligible participants will receive GIR for up to 8 weeks. The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.
• Placebo Comparator: Placebo
  • Eligible participants will receive Placebo for up to 8 weeks.The treatment period will consist of study product administration from day 0 through day 56 with a masked dose-escalation period from day 0 through day 49.

Clinical Trial Outcome Measures

Primary Measures

• Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
  • Time Frame: Baseline to Week 8
  • Change from baseline to Week 8 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient’s behavior in last 4 weeks.

Secondary Measures

• Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
  • Time Frame: Baseline to Week 4
  • Change from baseline to Week 4 of the ABC-H subscale score. The ABC-H is a subscale of the ABC. Each of the 16 items is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score range is 0 to 48, where a higher score indicates endorsement of greater hyperactivity. Rating based on patient’s behavior in last 4 weeks.
• Proportion of participants with a CGI-I score of 2 or better at Week 4
  • Time Frame: Baseline to Week 4
  • CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient’s illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
• Proportion of participants with a CGI-I score of 2 or better at Week 8
  • Time Frame: Baseline to Week 8
  • CGI-I specific to hyperactivity, inattention and impulsivity behaviors. The CGI-I is a seven-point scale that requires the clinician to assess how much the patient’s illness has improved or worsened relative to a baseline state at the beginning of the intervention. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.
• Safety of GIR (guanfacine immediate release)
  • Time Frame: Baseline through Week 8
  • Number of participants with adverse events (AEs), serious adverse events (SAEs), or events of special interest (ESIs).

Participating in This Clinical Trial

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 seizure within the last 6 months. 9. Participant has had a change in their anti-convulsant dose within the last 4 weeks. 10. 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. 11. 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). 12. Participant has untreated thyroid disease. 13. Participant has a known hepatic impairment defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN) for age. 14. Participant has known impending or renal failure defined as: 1. Anuria diagnosed within 12 hours prior to enrollment; 2. Requiring renal replacement therapy. 15. Participant is pregnant. 16. Participant has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study.

Gender Eligibility: All

Minimum Age: 6 Years

Maximum Age: 12 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • Rachel G. Greenberg, MD, MB, MHS
• Collaborator
  • The Emmes Company, LLC
• Provider of Information About this Clinical Study
  • Sponsor-Investigator: Rachel G. Greenberg, MD, MB, MHS, Associate Professor of Pediatrics – Duke University
• Overall Official(s)
  • Rachel Greenberg, Principal Investigator, DCRI
• Overall Contact(s)
  • Elena Soler, 919- 668-8503, elena.soler@duke.edu