Guanfacine for Hyperactivity in Children With Down Syndrome (HYPEbeGONE_DS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 15
- 主要终点
- Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
研究概览
简要总结
The primary 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.
详细描述
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. Participant data will be collected via a daily study diary and study measures completed 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
A masked investigational pharmacist or designee will dispense study product according to randomization treatment assignments. All other site staff as well as participants and parents/legal guardians will also be masked for up to 8 weeks while the study participant is receiving study product.
Participants, parents/legal guardians, site staff, and study administrators will be unmasked at the 8 week study visit.
Emergency unmasking may occur at any time throughout the study in the event that knowledge of the actual treatment is absolutely essential for further management of the participant.
入排标准
- 年龄范围
- 6 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •Participant has clinical diagnosis of non-mosaic DS.
- •Participant is between 6 and 12 years of age (inclusive) at time of consent.
- •Participant weight is ≥ 25 kg.
- •Participant has clinically significant symptoms of hyperactivity, inattention and impulsivity manifested as minimum scores of the following rating scales within 30 days of randomization:
- •A minimum score of 18 on the parent-reported ABC-H subscale, AND
- •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.
- •Participant has co-morbid medical screening and clearance to proceed with a non-stimulant medication trial with GIR within 30 days of randomization.
- •Participant is willing and able to comply with study procedures, including adherence to medication dosing schedule.
排除标准
- •Participant has received guanfacine (any formulation) within 30 days of randomization.
- •Participant has received any of the following concomitant medication classes within 30 days of randomization:
- •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)
- •Strong CYP3A4 inducers (e.g., avasimibe, carbamazepine, phenytoin, rifampin, and St. John's wort)
- •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
- •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.
- •Participant is currently in or plans to participate in another interventional study.
- •Participant has a known hypersensitivity to guanfacine.
- •Participant has had a previous guanfacine treatment failure, as determined by their primary treating physician.
- •Participant has had a change in another medication intended to treat symptoms of hyperactivity, inattention, and impulsivity within the last 2 weeks.
- •Participant has had a seizure within the last 6 months.
- •Participant has had a change in their anti-convulsant dose within the last 4 weeks.
- •Participant has a cardiac-related condition including:
- •Significant symptomatic bradycardia;
- •2nd degree or 3rd degree (complete) heart block;
- •Baseline heart rate (HR) or systolic blood pressure (BP) > 2 standard deviations (SD) below mean for age as determined by medical examination;
- •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;
- •Known history of congenital heart disease which requires ongoing care for monitoring or management will require clearance by cardiology prior to enrollment.
- •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).
- •Participant has untreated thyroid disease.
- •Participant has a known hepatic impairment defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN) for age.
- •Participant has known impending or renal failure defined as:
- •Anuria diagnosed within 12 hours prior to enrollment;
- •Requiring renal replacement therapy.
- •Participant is pregnant.
- •Participant has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study.
研究组 & 干预措施
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.
干预措施: Guanfacine Hydrochloride Immediate Release (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core
时间窗: 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.
次要结局
- Change in parent-rated ABC-H (Aberrant Behavior Checklist-Hyperactivity) subscale core(Baseline to Week 4)
- Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 4(Baseline to Week 4)
- Safety of GIR (guanfacine immediate release)(Baseline through Week 8)
- Proportion of participants with a CGI-I (Clinical Global Impression-Improvement) score of 2 or better at Week 8(Baseline to Week 8)
研究者
Rachel G. Greenberg, MD, MB, MHS
Associate Professor of Pediatrics
Duke University