Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS) (HYP01)

Rachel G. Greenberg, MD, MB, MHS

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Placebo; Drug: Guanfacine Hydrochloride Immediate Release

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT06042257

Pro00111256

HHSN275201800003I (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 6 to 12 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 2 patient groups, including a placebo group

Guanfacine Hydrochloride Immediate Release

Active Comparator group

Description:

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.

Treatment:

Drug: Guanfacine Hydrochloride Immediate Release

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo