Trial Outcomes & Findings for Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC) (NCT NCT04026113)

Last Updated: 2024-11-26

Results Overview

An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the bowel movement (BM) or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) were measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

438 participants

Primary outcome timeframe

Baseline, up to 12 weeks

Results posted on

2024-11-26

Participant Flow

The study was conducted at 64 sites, in 7 countries.

Participants were randomized in a 1:1 ratio for 12 weeks during the double-blind (DB) study intervention period: * FC participants received either linaclotide 72 μg or placebo * IBS-C participants received either linaclotide 145 μg or 290 μg Participants were considered to have completed the study after the DB and Post-Intervention periods. However, the Post-Intervention period was not required for those who enrolled into an open-label, long-term safety study after completing the DB period.

Participant milestones

Participant milestones
Measure	FC Participants: Placebo Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 145 μg Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 290 μg Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Double-Blind Treatment Period (12 Weeks) STARTED	164	166	55	53
Double-Blind Treatment Period (12 Weeks) Randomized and Treated	164	164	55	53
Double-Blind Treatment Period (12 Weeks) COMPLETED	145	148	52	46
Double-Blind Treatment Period (12 Weeks) NOT COMPLETED	19	18	3	7
Post-Intervention Period (1 Week) STARTED	66	75	20	20
Post-Intervention Period (1 Week) COMPLETED	65	75	19	20
Post-Intervention Period (1 Week) NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	FC Participants: Placebo Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 145 μg Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 290 μg Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Double-Blind Treatment Period (12 Weeks) Lack of Efficacy	1	2	0	1
Double-Blind Treatment Period (12 Weeks) Withdrawal by Subject	7	5	1	5
Double-Blind Treatment Period (12 Weeks) Lost to Follow-up	4	0	1	0
Double-Blind Treatment Period (12 Weeks) Physician Decision	1	1	1	0
Double-Blind Treatment Period (12 Weeks) Other, not specified	4	3	0	1
Double-Blind Treatment Period (12 Weeks) Adverse Event	2	2	0	0
Double-Blind Treatment Period (12 Weeks) Non-compliance with study drug	0	4	0	0
Double-Blind Treatment Period (12 Weeks) Protocol Violation	0	1	0	0
Post-Intervention Period (1 Week) Other, not specified	1	0	1	0

Baseline Characteristics

Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FC Participants: Placebo n=164 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=166 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 145 μg n=55 Participants Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 290 μg n=53 Participants Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	Total n=438 Participants Total of all reporting groups
Age, Customized 6-11 years	91 Participants n=5 Participants	92 Participants n=7 Participants	22 Participants n=5 Participants	21 Participants n=4 Participants	226 Participants n=21 Participants
Age, Customized 12-17 years	73 Participants n=5 Participants	74 Participants n=7 Participants	33 Participants n=5 Participants	32 Participants n=4 Participants	212 Participants n=21 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	96 Participants n=7 Participants	31 Participants n=5 Participants	34 Participants n=4 Participants	247 Participants n=21 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	70 Participants n=7 Participants	24 Participants n=5 Participants	19 Participants n=4 Participants	191 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	77 Participants n=5 Participants	72 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	185 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	87 Participants n=5 Participants	94 Participants n=7 Participants	36 Participants n=5 Participants	36 Participants n=4 Participants	253 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Black or African American	45 Participants n=5 Participants	42 Participants n=7 Participants	13 Participants n=5 Participants	14 Participants n=4 Participants	114 Participants n=21 Participants
Race (NIH/OMB) White	114 Participants n=5 Participants	116 Participants n=7 Participants	40 Participants n=5 Participants	35 Participants n=4 Participants	305 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, up to 12 weeks

Population: Modified Intent-to-Treat Population: all randomized participants who received at least 1 dose of double-blind study intervention. Participants with analysis values at both baseline and postbaseline during the specified time period.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=164 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=164 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Functional Constipation (FC) Participants: Change From Baseline in 12-week SBM (Spontaneous Bowel Movement) Frequency Rate (SBMs/Week) During the Study Intervention Period	1.050 SBMs Standard Error 0.187	2.220 SBMs Standard Error 0.187

PRIMARY outcome

Timeframe: 12 Weeks

6/12 weeks APS + 2 responder=participant who meets the weekly APS + 2 responder criteria ≥6 of the 12 weeks of the intervention period. Weekly APS +2 responder=participant who has an increase of ≥2 in the SBM weekly rate from baseline, AND a decrease of ≥30% in mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain and BM characteristics that determine occurrences of SBMs were measured by using an eDiary completed twice daily (AM and PM). Assessments of abdominal pain were measured using a 5-point scale where 0=none and 4=a lot. A participant's abdominal pain score=mean of the non-missing abdominal pain scores during the specified period. Responder rate=percentage of participants who were 6/12 weeks APS + 2 responders. A participant had to have ≥4 completed diary days in the analysis week to be considered a responder for that week and was otherwise considered a non-responder for that week.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=53 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=47 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks APS (Abdominal Pain and SBM) + 2 Responder Rate	22.6 percentage of participants	23.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, up to 12 weeks

Stool consistency was measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal pediatric Bristol Stool Form Scale (p-BSFS): Type 1: Looks like small hard lumps or balls, like pebbles; Type 2: Looks like fat sausage shape but lumpy and hard; Type 3: Looks like a sausage but with cracks on it; Type 4: Looks like a sausage or snake, smooth and soft; Type 5: Looks like chicken nuggets, soft smooth blobs; Type 6: Looks like oatmeal, fluffy mushy pieces; Type 7: Looks like a milkshake, watery. A participant's p-BSFS score for the study intervention period was the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=132 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=135 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Functional Constipation (FC) Participants: Change From Baseline in 12-week Stool Consistency During the Study Intervention Period	0.685 units on a scale Standard Error 0.078	1.108 units on a scale Standard Error 0.077

SECONDARY outcome

Timeframe: Baseline, up to 12 Weeks

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. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) were measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device. A participant's SBMs/week for the study intervention period was the average of the non-missing SBMs/week reported by the participant during the 12-week study intervention period.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=53 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=47 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week SBM Frequency Rate (SBMs/Week) During the Study Intervention Period	2.347 SBMs/week Standard Deviation 3.3335	2.747 SBMs/week Standard Deviation 2.8861

SECONDARY outcome

Timeframe: Baseline, up to 12 weeks

Assessments of abdominal pain were measured twice daily, once in the morning and once in the evening eDiary, using a 5-point scale where a score of 0 indicates no abdominal pain scores and a score of 4 indicates a lot of abdominal pain. Assessments of abdominal pain were measured using a 5-point scale where '0' indicates no abdominal pain and '4' indicates a lot of abdominal pain. The participant's abdominal pain score was derived as the mean of the non-missing morning and evening abdominal pain scores during the specified period.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=53 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=47 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week Abdominal Pain During the Study Intervention Period	-0.837 units on a scale Standard Deviation 0.9313	-0.837 units on a scale Standard Deviation 0.8809

SECONDARY outcome

Timeframe: Baseline, up to 12 weeks

Stool consistency was measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery. A participant's p-BSFS score for the study intervention period was the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=47 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=39 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week Stool Consistency During the Study Intervention Period	0.979 units on a scale Standard Deviation 1.2900	1.358 units on a scale Standard Deviation 1.1288

SECONDARY outcome

Timeframe: 12 weeks

A 6/12 weeks SBM + 2 responder is a participant that meets the weekly SBM + 2 responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly SBM +2 responder is a participant who has an increase of at least 2 in the SBM weekly rate from baseline, Assessments of BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) were measured by using an eDiary completed twice daily (morning and evening). Responder rate is presented as the percentage of participants who were 6/12 weeks SBM + 2 responders.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=53 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=47 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks SBM + 2 Responder Rate	30.2 percentage of participants	29.8 percentage of participants

SECONDARY outcome

Timeframe: 12 Weeks

A 6/12 weeks abdominal pain responder is a participant that meets the weekly abdominal pain responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly abdominal pain responder is a participant who has a decrease of at least 30% in the mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain were measured by using an eDiary completed twice daily (morning and evening) and were measured using a 5-point scale where '0' indicates no abdominal pain and '4' indicates a lot of abdominal pain. The participant's abdominal pain score was derived as the mean of the non-missing abdominal pain scores during the specified period. Responder rate is presented as the percentage of participants who were 6/12 weeks abdominal pain responders.

Outcome measures

Outcome measures
Measure	FC Participants: Placebo n=53 Participants Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Linaclotide 72 μg n=47 Participants Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks Abdominal Pain Responder	49.1 percentage of participants	42.6 percentage of participants

Adverse Events

FC Participants: Linaclotide 72 μg

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

FC Participants: Placebo

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

IBS-C Participants: Linaclotide 145 μg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

IBS-C Participants: Linaclotide 290 μg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	FC Participants: Linaclotide 72 μg n=166 participants at risk Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Placebo n=164 participants at risk Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 145 μg n=55 participants at risk Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 290 μg n=53 participants at risk Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Gastrointestinal disorders DIARRHOEA	0.60% 1/166 • Number of events 1 • Up to 13 weeks All randomized participants	0.00% 0/164 • Up to 13 weeks All randomized participants	0.00% 0/55 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants
Gastrointestinal disorders FAECALOMA	0.60% 1/166 • Number of events 1 • Up to 13 weeks All randomized participants	0.00% 0/164 • Up to 13 weeks All randomized participants	0.00% 0/55 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants
Psychiatric disorders SUICIDAL IDEATION	0.00% 0/166 • Up to 13 weeks All randomized participants	0.61% 1/164 • Number of events 1 • Up to 13 weeks All randomized participants	0.00% 0/55 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants
Psychiatric disorders SUICIDE ATTEMPT	0.00% 0/166 • Up to 13 weeks All randomized participants	1.2% 2/164 • Number of events 2 • Up to 13 weeks All randomized participants	0.00% 0/55 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants

Other adverse events

Other adverse events
Measure	FC Participants: Linaclotide 72 μg n=166 participants at risk Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	FC Participants: Placebo n=164 participants at risk Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 145 μg n=55 participants at risk Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	IBS-C Participants: Linaclotide 290 μg n=53 participants at risk Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
Gastrointestinal disorders ABDOMINAL PAIN	0.60% 1/166 • Number of events 1 • Up to 13 weeks All randomized participants	1.2% 2/164 • Number of events 2 • Up to 13 weeks All randomized participants	3.6% 2/55 • Number of events 2 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants
Gastrointestinal disorders CONSTIPATION	0.60% 1/166 • Number of events 1 • Up to 13 weeks All randomized participants	0.00% 0/164 • Up to 13 weeks All randomized participants	3.6% 2/55 • Number of events 2 • Up to 13 weeks All randomized participants	0.00% 0/53 • Up to 13 weeks All randomized participants
Gastrointestinal disorders DIARRHOEA	3.6% 6/166 • Number of events 6 • Up to 13 weeks All randomized participants	1.8% 3/164 • Number of events 3 • Up to 13 weeks All randomized participants	7.3% 4/55 • Number of events 4 • Up to 13 weeks All randomized participants	7.5% 4/53 • Number of events 4 • Up to 13 weeks All randomized participants
Infections and infestations COVID-19	2.4% 4/166 • Number of events 4 • Up to 13 weeks All randomized participants	3.0% 5/164 • Number of events 5 • Up to 13 weeks All randomized participants	3.6% 2/55 • Number of events 2 • Up to 13 weeks All randomized participants	1.9% 1/53 • Number of events 1 • Up to 13 weeks All randomized participants

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place