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, A Multicenter, Randomized, Double-blind, Placebo-controlled Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 7-17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) (ie, Fulfill Rome III Criteria for Child/Adolescent IBS and Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 101
- 试验地点
- 47
- 主要终点
- Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of linaclotide for the treatment of Irritable Bowel syndrome with Constipation (IBS-C), in children age 7-17 years.
This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Patients age 7-11 will receive oral liquid or oral solid capsule and patients 12-17 will receive solid oral capsule formulation. Children ages 7-11 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 IBS-C.
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
- 7 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient weighs at least 18 kg (39.7 lbs)
- •Patient meets Rome III criteria for child/adolescent IBS: at least once per week for at least 2 months before Screening Visit, the patient 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:
- •a) Improvement with defecation
- •b) Onset associated with a change in frequency of stool
- •c) Onset associated with a change in form (appearance) of stool
- •Patient meets modified Rome III criteria for child/adolescent Functional Constipation (FC): For at least 2 months before the Screening Visit, the patient 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 fecal mass in the rectum
- •d) History of large diameter stools that may obstruct the toilet
- •Patient is willing to discontinue any laxatives used before the Pretreatment Visit in favor of the protocol-permitted rescue medicine
- •Patient 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
- •Patient or parent/guardian/LAR or caregiver is compliant with 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
- •Patient 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
- •Patient has required manual disimpaction anytime prior to randomization or disimpaction during in-patient hospitalization within one year prior to randomization
- •Patient is unable to tolerate the placebo during rhe Screening Period
研究组 & 干预措施
Linaclotide Dose A
Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast.
Dose A: 18 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg
Dose A: 36 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg
Dose A: 36 micrograms solid oral capsule in children 12-17 years of age
干预措施: Linaclotide Dose A (Drug)
Linaclotide Dose B
Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast.
Dose B: 36 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg
Dose B: 72 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg
Dose B: 72 micrograms solid oral capsule in children 12-17 years of age
干预措施: Linaclotide Dose B (Drug)
Linaclotide Dose C
Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast.
Dose C: 72 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg
Dose C: 145 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg
Dose C: 145 micrograms solid oral capsule in children 12-17 years of age
干预措施: Linaclotide Dose C (Drug)
Linaclotide Approved Adult Dose
Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast.
Approved Adult Dose: 290 micrograms solid oral capsule in children 12-17 years of age
干预措施: Linaclotide Approved Adult Dose (Drug)
Matching Placebo
Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast
Placebo liquid oral solution or placebo solid oral capsule in children 7-11 years of age
Placebo solid oral capsule in children 12-17 years of age
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period
时间窗: Baseline (14 days 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.
次要结局
- Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms(Baseline (14 days prior to randomization) to week 4)
- Change From Baseline in 4-week Stool Consistency(Baseline (14 days prior to randomization and up to randomization) to week 4)
- Change From Baseline in 4-week Severity of Straining(Baseline (14 days prior to randomization and up to randomization) to week 4)
- Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment(Baseline (14 days prior to randomization) to week 4)
- Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)(Baseline (14 days prior to randomization and up to randomization) to week 4)