A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Efficacy and Safety of Plecanatide in Children and Adolescents Age 6 to <18 Years of Age With Functional Constipation (FC)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency at Week 8
研究概览
简要总结
The goal of this clinical trial is to learn if plecanatide can treat functional constipation in children and adolescents aged 6 to less than 18 years. It will also learn about the safety and pharmacokinetics of plecanatide in this population. The main questions it aims to answer are:
- Does plecanatide increase the number of spontaneous bowel movements compared to placebo after 8 weeks of treatment?
- What medical problems do participants experience when taking plecanatide? Researchers will compare low-dose plecanatide and high-dose plecanatide to placebo to see if plecanatide improves bowel movement frequency, stool consistency, and constipation-related symptoms.
Participants will:
- Complete a screening period with daily electronic diary entries to record bowel movements, symptoms, and rescue medication use
- Take plecanatide or placebo by mouth once daily for 8 weeks
- Continue daily electronic diary entries throughout the study
- Attend clinic visits for physical exams, laboratory tests, and assessments of symptoms and safety
- Provide blood samples for pharmacokinetic and safety evaluations
- Complete questionnaires about constipation symptoms and quality of life
详细描述
This Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of plecanatide administered orally once daily in pediatric participants with functional constipation (FC). Approximately 180 participants will be enrolled at up to 30 investigational sites in the United States and randomized in a 1:1:1 ratio to receive low-dose plecanatide, high-dose plecanatide, or matching placebo. Randomization will be stratified by age group (6 to 11 years and 12 to less than 18 years) and sex.
Background and Rationale Functional constipation is a common condition in children and adolescents and is characterized by infrequent bowel movements, hard stool consistency, and associated symptoms such as straining and abdominal discomfort. Available treatment options in the pediatric population are limited, and there remains a need for additional therapies.
Plecanatide is an orally administered guanylate cyclase-C (GC-C) agonist that acts locally in the gastrointestinal tract to increase intestinal fluid secretion and transit. Clinical studies in adults with chronic idiopathic constipation have demonstrated improvements in bowel movement frequency and stool consistency, as well as an acceptable safety profile. The current study is designed to evaluate plecanatide in a pediatric population using a weight-based dosing approach intended to achieve exposure levels comparable to those associated with efficacy in adults.
Study Design The study consists of three periods: a Screening/Baseline Period, an 8-week Treatment Period, and a Post-treatment Follow-up Period. The total duration of participation is approximately 14 weeks (98 days).
During the Screening/Baseline Period (up to 28 days), participants and/or caregivers complete daily assessments using an electronic diary (eDiary) to record bowel movements, stool characteristics, and constipation-related symptoms. Data from the eDiary are used to establish baseline values and confirm eligibility prior to randomization.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study in which participants, investigators, study site personnel, and outcome assessors are unaware of treatment assignments. Matching placebo tablets are identical in appearance to active study drug to maintain the blind. Randomization codes are generated and maintained by an interactive web-based randomization system. Treatment assignments will be unblinded only after database lock, unless unblinding is required for participant safety in a medical emergency.
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female children and adolescents aged 6 to <18 years at time of consent.
- •Diagnosis of functional constipation (FC) based on Rome IV criteria for children/adolescents.
- •Participant and/or legally authorized representative able to provide informed consent/assent.
- •Participant/caregiver willing and able to comply with study procedures, including electronic diary (eDiary).
- •Completion of ≥5 out of 7 daily diary entries during each of the 2 baseline weeks.
- •Stable diet for at least 14 days prior to screening.
- •Females of childbearing potential must use highly effective contraception and have negative pregnancy tests.
排除标准
- •Weight <15 kg at screening/randomization.
- •History of anorectal malformations, neurological deficits, or anatomical abnormalities affecting bowel function.
- •Use of prohibited medications within 15 days prior to randomization (e.g., anticholinergics, 5-HT agents, opioids, other laxatives).
- •Use of any laxatives other than study-provided Dulcolax®.
- •Pregnant or breastfeeding participants.
- •Active eating disorder within the past 6 months.
- •Clinically significant medical conditions (hepatic, renal, gastrointestinal, endocrine, infectious) that may interfere with study.
- •Known hypersensitivity to plecanatide.
- •History of drug or alcohol abuse within 12 months.
- •Participation in another clinical trial within 30 days.
- •Non-compliance with eDiary requirements (<5/7 entries per week).
- •Use of rescue medication more than 2 days per week during baseline.
- •≥3 spontaneous bowel movements (SBMs) per week during baseline.
研究组 & 干预措施
Placebo
Participants will receive matching placebo orally once daily for 8 weeks.
干预措施: Placebo (Drug)
Low Dose Plecanatide
Participants will receive weight-based low-dose plecanatide administered orally once daily for 8 weeks.
干预措施: plecanatide (Drug)
High Dose Plecanatide
Participants will receive weight-based high-dose plecanatide orally once daily for 8 weeks.
干预措施: plecanatide (Drug)
结局指标
主要结局
Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency at Week 8
时间窗: Baseline to week 8
Spontaneous bowel movements (SBMs) are defined as bowel movements that occur without the use of rescue medication within the preceding 24 hours. Weekly SBM frequency will be calculated based on daily electronic diary entries. The endpoint is the change from baseline in the number of SBMs per week at Week 8.
次要结局
- Proportion of Participants Who Are SBM Responders at Week 8(week 8)
- Change From Baseline in Weekly Complete Spontaneous Bowel Movement (CSBM) Frequency at Week 8(Baseline to week 8)
- Change From Baseline in Stool Consistency as Measured by the Bristol Stool Form Scale (BSFS) at Week 8(Baseline to week 8)
- Time to First Spontaneous Bowel Movement (SBM)(up to 8 weeks)
- Use of Rescue Medication Over 8 Weeks(Baseline and Weeks 1 through 8)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(Up to 10 weeks)