A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children, Ages 6 to 17 Years, Who Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation (FC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 173
- 试验地点
- 61
- 主要终点
- Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period
研究概览
简要总结
The purpose of this study was to evaluate dose response of the safety and efficacy of linaclotide for the treatment of functional constipation (FC), in children age 6-17 years. This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Participants age 6-11 years will receive oral liquid formulation and participants 12-17 years will receive solid oral capsule or liquid oral solution.
Children ages 6-11 years meeting the entry criteria will be randomized to 1 of 3 doses of linaclotide or placebo for 4 weeks. Children ages 12-17 years meeting the entry criteria will be randomized to 1 of 4 doses of linaclotide or placebo for 4 weeks.
This 4-week study will assess the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of FC.
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)
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
- •Participant weighs at least 18 kg (kilograms) (39.7 lbs)
- •Participant meets modified Rome III criteria for child/adolescent FC: For at least 2 months before the Screening Visit, the participant has had 2 or fewer defecations (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) in the toilet per week. In addition, at least once per week, patient meets 1 or more of the following:
- •a) History of retentive posturing or excessive volitional stool retention
- •b) History of painful or hard bowel movements (BMs)
- •c) Presence of a large faecal mass in the rectum
- •d) History of large diameter stools that may obstruct the toilet
- •e) At least one episode of fecal incontinence per week
- •Participant is willing to discontinue any laxatives used before the Pretreatment Visit in favor of the protocol-permitted rescue medicine
- •Participant has an average of fewer than 3 spontaneous BMs (SBMs) per week during the 14 days before the randomization day and up to the randomization. An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM
- •Participant or participant/guardian/legally authorized representative (LAR) or caregiver is compliant with electronic diary (eDiary) by completing both the morning and evening assessments for 10 out of the 14 days immediately preceding the Randomization Visit
排除标准
- •Participant meets Rome III criteria for Child/Adolescent irritable bowel syndrome (IBS): At least once per week for at least 2 months before the Screening Visit, the participant has experienced abdominal discomfort (an uncomfortable sensation not described as pain) or pain associated with 2 or more of the following at least 25% of the time:
- •Improvement with defecation
- •Onset associated with a change in frequency of stool
- •Onset associated with a change in form (appearance) of stool
- •Participant reports having more than 1 loose, mushy stool (eDiary-recorded stool consistency of 6 on the Pediatric Bristol Stool Form Scale [p-BSFS]) or any watery stool (eDiary-recorded stool consistency of 7 on the p-BSFS) with any SBM that occurred in the absence of laxative use on the calendar day of the BM or the calendar day before the BM during the 14 days before the randomization day and up to the randomization
- •Select medical history or conditions that may be related to other causes of constipation or may interfere with safety and efficacy analyses
- •Participant has required manual or hospital-based disimpassion any time prior to randomization
- •Participant is unable to tolerate the placebo during the Screening Period
研究组 & 干预措施
Placebo
Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age.
干预措施: Placebo (Drug)
LIN Dose A (9 ug or 18 ug)
Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.
干预措施: LIN Dose A (Drug)
LIN Dose B (18 ug or 36 ug)
Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.
干预措施: LIN Dose B (Drug)
LIN Dose C (36 ug or 72 ug)
Participants aged 6 to 11 years with weight 18 to <35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.
干预措施: LIN Dose C (Drug)
LIN 145 µg
Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.
干预措施: LIN 145 µg (Drug)
结局指标
主要结局
Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period
时间窗: Baseline (14-day prior to randomization and up to randomization) to Week 4
SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. SBM rate was defined as SBMs/week during the 4-week Treatment period. Participants recorded the occurrence of BMs and use of rescue medication, morning and evening, daily in an eDiary since pretreatment period. The SBM frequency rate (SBMs/week) during the analysis period for each participant were calculated as \[(total number of SBMs in the analysis period/number of days in the analysis period)\*7\]. Baseline value was based on values collected 14 days before randomization up to randomization. Change from Baseline was calculated as the SBM frequency rate during the 4-week treatment period - SBM frequency rate at baseline. A positive change from Baseline indicates improvement. Least squares mean (LSM) and standard error (SE) were calculated using analysis of covariance (ANCOVA) method.
次要结局
- Change From Baseline (CFB) in 4-week of Severity of Straining(Baseline (14-day prior to randomization and up to randomization) to Week 4)
- Change From Baseline (CFB) in 4-week Daytime Abdominal Pain(Baseline (14-day prior to randomization) to Week 4)
- Change From Baseline (CFB) in 4-week Stool Consistency(Baseline (14-day prior to randomization and up to randomization) to Week 4)
- Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment(Baseline (14-day prior to randomization) to Week 4)
- Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period(Baseline (14-day prior to randomization and up to randomization) to Week 4)
- Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment(Baseline (14-day prior to randomization) to Week 4)