Trial · Interventional

TerminatedPhase 2Results postedRegistry data

A Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 7-17 Years, With Irritable Bowel Syndrome With Constipation

Short name LIN-MD-63

NCTNCT02559817Other idLIN-MD-63

Open at ClinicalTrials.govAsk about this trial

This trial was stopped early.

The registry gives no reason.

Results were posted for this trial.

Overview

Status: Terminated
Phase: Phase 2
Enrollment: 101 participants (actual)
Sponsor: Forest Laboratories · Industry
Design: Randomized · Quadruple masking
Countries: 2 countries
United States, Canada
Start: 1 Nov 2015
Primary completion: 30 Aug 2019
Completion: 30 Aug 2019
First posted: 24 Sept 2015 (estimated)
Last update posted: 28 Dec 2020
Conditions: Irritable Bowel Syndrome With Constipation

Timeline

1 trial · 1 stopped early · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

201520162017201820192020

Ph 2
LIN-MD-63
NCT02559817
1 Nov 2015 to 30 Aug 2019
Terminated
Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Linaclotide Dose ADrug
Linaclotide Dose BDrug
Linaclotide Dose CDrug
Linaclotide Approved Adult DoseDrug
Matching PlaceboDrug

Arms5

Experimental
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
Experimental
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
Experimental
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
Experimental
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
Placebo comparator
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

Primary outcomes1

Outcomes the sponsor listed as primary.

Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period
Time frame · Baseline (14 days prior to randomization and up to randomization) to week 4
Registry description
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.

Secondary outcomes(5)

Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms
Time frame · Baseline (14 days prior to randomization) to week 4
Registry description
The abdominal pain score was measured using 5-point scale. Participants answered the questions, How much did your tummy hurt as: 0=none, 1=a tiny bit, 2=a little, 3=some, and 4=a lot. The 4-week daytime abdominal pain was calculated as the average of nonmissing scores in evening eDiary during the Treatment Period with higher value indicating greater symptom severity. Baseline value was the average of non-missing values collected 14 days before randomization. Change from Baseline was calculated as the daytime abdominal pain score during the 4-week treatment period (i.e. average of non-missing daytime scores during 4-week treatment period) - daytime abdominal pain score at baseline. A negative change from Baseline indicates improvement.
Change From Baseline in 4-week Stool Consistency
Time frame · Baseline (14 days prior to randomization and up to randomization) to week 4
Registry description
Participants used 7-point pediatric Bristol Stool Form (p-BSFS) scale to rate stool consistency for each BM in morning and evening eDiary where 1=small hard lumps or balls like pebbles,2=fat sausage shape but lumpy and hard,3=a sausage but with cracks on it,4=sausage or snake, smooth and soft,5=chicken nuggets, soft smooth blobs,6=oatmeal, fluffy mushy pieces,7=milkshake, watery. Scores in 4-week treatment period were calculated as mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period. Baseline value was based on values collected 14 days before randomization up to randomization.
Change From Baseline in 4-week Severity of Straining
Time frame · Baseline (14 days prior to randomization and up to randomization) to week 4
Registry description
Severity of straining was scored on 5-point scale for question-When you pooped, how hard did you push? The score ranges from 0= not hard at all,1= I pushed a tiny bit hard,2= I pushed a little hard,3= I pushed hard,4= I pushed very hard with higher scores indicating more severe straining. Participants recorded degree of straining for each BM in morning and evening eDiary. Scores during 4-week treatment period were calculated as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period.
Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment
Time frame · Baseline (14 days prior to randomization) to week 4
Registry description
Participants recorded their assessment of abdominal bloating in the evening eDiary. Participants answered the question: How big and full did your tummy feel? on a scale, where: 0=none, 1=a tiny bit, 2=a little, 3=medium or 4=very, with a higher score indicating more severe bloating. Baseline value was the average of values collected 14 days before randomization. The 4-week daytime abdominal bloating symptoms were calculated as the average of non-missing scores reported in the evening eDiary during the treatment period. Change from Baseline was calculated as the 4-week daytime abdominal bloating score during the treatment period - daytime abdominal bloating score at baseline. A negative change from Baseline indicates improvement.
Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)
Time frame · Baseline (14 days prior to randomization and up to randomization) to week 4
Registry description
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. A CSBM was an SBM that was associated with a sense of complete evacuation. Participants recorded their assessment of the sensation of incomplete evacuation for each BM in the morning and evening eDiary. The 4-week overall CSBM frequency rate was calculated as \[total number of CSBMs in the analysis period/number of days in the analysis period\]\*7). Baseline value was based on values collected 14 days before randomization and up to randomization. Change from Baseline was calculated as the CSBM frequency rate during the 4-week treatment period - CSBM frequency rate at baseline. A positive change from Baseline indicates improvement.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (14 days prior to randomization and up to randomization) to week 4

Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period

Group	Value (Spontaneous Bowel Movements per Week)	Spread
Matching Placebo	1.447	1.376
Linaclotide Dose A	1.991	2.349
Linaclotide Dose B	2.298	2.634
Linaclotide Dose C	2.678	2.774
Linaclotide Approved Adult Dose	3.222	2.194

Secondary and other outcome results(5)

Secondary outcomeMean· Baseline (14 days prior to randomization) to week 4

Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms

Group	Value (Units on a Scale)	Spread
Matching Placebo	-0.654	0.789
Linaclotide Dose A	-0.709	0.977
Linaclotide Dose B	-0.565	0.861
Linaclotide Dose C	-0.648	0.948
Linaclotide Approved Adult Dose	-1.192	1.032

Secondary outcomeMean· Baseline (14 days prior to randomization and up to randomization) to week 4

Change From Baseline in 4-week Stool Consistency

Group	Value (Units on a Scale)	Spread
Matching Placebo	0.653	0.949
Linaclotide Dose A	1.200	1.068
Linaclotide Dose B	1.502	1.272
Linaclotide Dose C	2.054	1.349
Linaclotide Approved Adult Dose	1.345	0.813

Secondary outcomeMean· Baseline (14 days prior to randomization and up to randomization) to week 4

Change From Baseline in 4-week Severity of Straining

Group	Value (Units on a Scale)	Spread
Matching Placebo	-0.576	0.915
Linaclotide Dose A	-0.782	1.187
Linaclotide Dose B	-0.859	0.993
Linaclotide Dose C	-1.222	0.972
Linaclotide Approved Adult Dose	-1.236	1.042

Secondary outcomeMean· Baseline (14 days prior to randomization) to week 4

Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment

Group	Value (Units on a Scale)	Spread
Matching Placebo	-0.438	0.754
Linaclotide Dose A	-0.486	0.974
Linaclotide Dose B	-0.515	0.992
Linaclotide Dose C	-0.440	0.823
Linaclotide Approved Adult Dose	-0.595	1.284

Secondary outcomeMean· Baseline (14 days prior to randomization and up to randomization) to week 4

Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)

Group	Value (CSBMs per Week)	Spread
Matching Placebo	0.825	1.211
Linaclotide Dose A	0.644	1.029
Linaclotide Dose B	1.167	1.822
Linaclotide Dose C	1.721	2.292
Linaclotide Approved Adult Dose	2.358	2.199

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Matching PlaceboTaken once daily each evening, at least 30 minutes before their evening meal, 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	0 / 19	1 / 19	3 / 19
Linaclotide Dose ATaken once daily each evening, at least 30 minutes before their evening meal, 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	0 / 29	1 / 29	6 / 29
Linaclotide Dose BTaken once daily each evening, at least 30 minutes before their evening meal, 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	0 / 21	0 / 21	5 / 21
Linaclotide Dose CTaken once daily each evening, at least 30 minutes before their evening meal,, 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	0 / 24	0 / 24	3 / 24
Linaclotide Approved Adult DoseTaken once daily each evening, at least 30 minutes before their evening meal, 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	0 / 8	0 / 8	1 / 8

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2024

4 results

Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.

Di Lorenzo et al. 2024Journal of pediatric gastroenterology and nutritioncited by 5

PMID 38504394DOI 10.1002/jpn3.12103PUB-38504394

Full text at the publisher4 results

Publisher page See results (4)

Eligibility

Who could join, as posted.

Sex: All
Age: from 7 Years up to 17 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * 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 Exclusion Criteria: * 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

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