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CompletedNCT02559570Updated Jun 19, 2019Results posted

A Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 6-17 Years Who Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation (FC)

A Phase 2 interventional study of Placebo and LIN Dose A in Functional Constipation in Children Ages 6-17 Years, sponsored by Forest Laboratories. Completed at 62 sites in 2 countries. Open to participants aged 6 Years to 17 Years. Per ClinicalTrials.gov, last updated 2019-06-19.

Sponsored by Forest Laboratories · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
173
Allocation
Randomized
Ages
6 Years to 17 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Functional Constipation in Children Ages 6-17 Years

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Keywords

  • Functional constipation in children
  • LINZESS
03

In context

Constipation

1,018 studies on the registry are indexed under Constipation; 139 are open to participants now.

This study's enrollment of 173 is above the median of 80 across 850 interventional studies indexed under Constipation.

Browse Constipation studies →

Lead sponsor

Forest Laboratories is the lead sponsor of 165 studies on the registry; none are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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:
    1. Improvement with defecation
    1. Onset associated with a change in frequency of stool
    1. 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
173 participants (actual)

Study arms

  • Placebo comparator
    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.

    Drug: Placebo

  • Experimental
    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.

    Drug: LIN Dose A

  • Experimental
    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.

    Drug: LIN Dose B

  • Experimental
    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.

    Drug: LIN Dose C

  • Experimental
    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.

    Drug: LIN 145 µg

Interventions

  • DrugPlacebo

    Participants received matching placebo LIN liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

  • DrugLIN Dose A

    Participants received LIN 9 or 18 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

    Also known as: LINZESS

  • DrugLIN Dose B

    Participants received LIN 18 or 36 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

    Also known as: LINZESS

  • DrugLIN Dose C

    Participants received LIN 36 or 72 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

    Also known as: LINZESS

  • DrugLIN 145 µg

    Participants received LIN 145 µg, liquid solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

    Also known as: LINZESS

06

What researchers measure

Primary outcomes

  1. Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period

    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.

    Time frame: Baseline (14-day prior to randomization and up to randomization) to Week 4

Secondary outcomes

  1. Change From Baseline (CFB) in 4-week Daytime Abdominal Pain

    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. LSM and SE were calculated using ANCOVA method.

    Time frame: Baseline (14-day prior to randomization) to Week 4

  2. Change From Baseline (CFB) in 4-week Stool Consistency

    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 by 2 approaches-1) following derivation similar in earlier adult studies, mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period (adult derivation),2) observed weighted average of daily p-BSFS scores during that period. Daily p-BSFS score was average of non-missing morning and/or evening assessments of p-BSFS score from SBMs reported by participants on that specific day. Baseline value was based on values collected 14 days before randomization up to randomization. LSM and SE were calculated using ANCOVA method.

    Time frame: Baseline (14-day prior to randomization and up to randomization) to Week 4

  3. Change From Baseline (CFB) in 4-week of Severity of Straining

    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. Data was derived as adult derivation and weighted average. Scores during 4-week treatment period were calculated following two approaches - (1) following derivation similar in earlier adult studies, as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period (adult derivation) and (2) as observed weighted average of daily straining scores during that period. Daily straining score was the average of non-missing morning and/or evening assessments of straining score from the SBMs reported by the participants on that specific day. LSM and SE were calculated using ANCOVA method.

    Time frame: Baseline (14-day prior to randomization and up to randomization) to Week 4

  4. Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment

    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. LSM and SE were calculated using ANCOVA method.

    Time frame: Baseline (14-day prior to randomization) to Week 4

  5. Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period

    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. LSM and SE were calculated using ANCOVA method.

    Time frame: Baseline (14-day prior to randomization and up to randomization) to Week 4

  6. Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment

    Participants recorded the presence of incontinence episodes in daytime daily since pre-treatment period (14-day prior to randomization) in the evening eDiary for participants randomized following protocol amendment #3. The 4-week daytime fecal incontinence was calculated as the mean of non-missing participant scores reported in the evening eDiary during the Treatment Period. Baseline value was the average of values collected 14 days before randomization. Change from Baseline was calculated as the 4-week fecal incontinence daytime symptoms during the treatment period - fecal incontinence daytime symptoms at baseline. A negative change from Baseline indicates improvement. No data is reported for LIN 145 μg as it was an exploratory arm group.

    Time frame: Baseline (14-day prior to randomization) to Week 4

07

Results

Posted May 14, 2019

Participant flow

Participant flow — Overall Study
MilestonePlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µg
Started4136413916
Completed3934393614
Not completed22232
Withdrew: Adverse event02010
Withdrew: Withdrawal of consent00121
Withdrew: Lost to follow-up10000
Withdrew: Protocol violation10001
Withdrew: Other miscellaneous reasons00100

Outcome measures

SecondaryChange From Baseline (CFB) in 4-week Daytime Abdominal Pain

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. LSM and SE were calculated using ANCOVA method.

Time frame:
Baseline (14-day prior to randomization) to Week 4
Reported as:
Least squares mean · score on a scale
Change From Baseline (CFB) in 4-week Daytime Abdominal Pain
score on a scalePlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
Change From Baseline (CFB) in 4-week Daytime Abdominal Pain-0.291 ± 0.102-0.333 ± 0.108-0.289 ± 0.102-0.171 ± 0.103
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.7789 · Least squares mean difference: -0.042 · 95% CI -0.335 to 0.252ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.9930 · Least squares mean difference: 0.001 · 95% CI -0.282 to 0.284ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.4107 · Least squares mean difference: 0.120 · 95% CI -0.167 to 0.408ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
PrimaryChange From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period

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.

Time frame:
Baseline (14-day prior to randomization and up to randomization) to Week 4
Reported as:
Least squares mean · SBMs/week
Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period
SBMs/weekPlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period2.000 ± 0.3941.412 ± 0.4221.814 ± 0.3972.364 ± 0.403
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.3097 · Least squares mean difference: -0.588 · 95% CI -1.729 to 0.552ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.7384 · Least squares mean difference: -0.186 · 95% CI -1.286 to 0.913ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.5188 · Least squares mean difference: 0.364 · 95% CI -0.748 to 1.477ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
SecondaryChange From Baseline (CFB) in 4-week Stool Consistency

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 by 2 approaches-1) following derivation similar in earlier adult studies, mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period (adult derivation),2) observed weighted average of daily p-BSFS scores during that period. Daily p-BSFS score was average of non-missing morning and/or evening assessments of p-BSFS score from SBMs reported by participants on that specific day. Baseline value was based on values collected 14 days before randomization up to randomization. LSM and SE were calculated using ANCOVA method.

Time frame:
Baseline (14-day prior to randomization and up to randomization) to Week 4
Reported as:
Least squares mean · score on a scale
Change From Baseline (CFB) in 4-week Stool Consistency
score on a scalePlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
CFB at Week 4 (Adult derivation)0.690 ± 0.1740.641 ± 0.1770.652 ± 0.1741.046 ± 0.172
CFB at Week 4 (Weighted average)0.668 ± 0.1670.606 ± 0.1700.594 ± 0.1660.930 ± 0.165
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.8426 · Least squares mean difference: -0.050 · 95% CI -0.543 to 0.444ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.8770 · Least squares mean difference: -0.038 · 95% CI -0.525 to 0.448ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.1502 · Least squares mean difference: 0.356 · 95% CI -0.131 to 0.842ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.7949 · Least squares mean difference: -0.062 · 95% CI -0.535 to 0.410ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.7543 · Least squares mean difference: -0.074 · 95% CI -0.540 to 0.392ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.2676 · Least squares mean difference: 0.262 · 95% CI -0.204 to 0.728ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
SecondaryChange From Baseline (CFB) in 4-week of Severity of Straining

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. Data was derived as adult derivation and weighted average. Scores during 4-week treatment period were calculated following two approaches - (1) following derivation similar in earlier adult studies, as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period (adult derivation) and (2) as observed weighted average of daily straining scores during that period. Daily straining score was the average of non-missing morning and/or evening assessments of straining score from the SBMs reported by the participants on that specific day. LSM and SE were calculated using ANCOVA method.

Time frame:
Baseline (14-day prior to randomization and up to randomization) to Week 4
Reported as:
Least squares mean · score on a scale
Change From Baseline (CFB) in 4-week of Severity of Straining
score on a scalePlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
CFB at Week 4 (Adult derivation)-0.657 ± 0.145-0.710 ± 0.150-0.778 ± 0.147-0.893 ± 0.145
CFB at Week 4 (Weighted average)-0.656 ± 0.143-0.710 ± 0.149-0.769 ± 0.145-0.855 ± 0.143
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.7997 · Least squares mean difference: -0.053 · 95% CI -0.465 to 0.359ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.5602 · Least squares mean difference: -0.121 · 95% CI -0.530 to 0.288ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.2529 · Least squares mean difference: -0.236 · 95% CI -0.641 to 0.170ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.7923 · Least squares mean difference: -0.054 · 95% CI -0.461 to 0.352ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.5802 · Least squares mean difference: -0.113 · 95% CI -0.517 to 0.290ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.3263 · Least squares mean difference: -0.199 · 95% CI -0.600 to 0.201ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
SecondaryChange From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment

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. LSM and SE were calculated using ANCOVA method.

Time frame:
Baseline (14-day prior to randomization) to Week 4
Reported as:
Least squares mean · score on a scale
Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment
score on a scalePlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment-0.314 ± 0.104-0.266 ± 0.110-0.287 ± 0.104-0.275 ± 0.105
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.7507 · Least squares mean difference: 0.048 · 95% CI -0.252 to 0.349ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.8505 · Least squares mean difference: 0.028 · 95% CI -0.262 to 0.317ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.7933 · Least squares mean difference: 0.039 · 95% CI -0.254 to 0.332ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
SecondaryChange From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period

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. LSM and SE were calculated using ANCOVA method.

Time frame:
Baseline (14-day prior to randomization and up to randomization) to Week 4
Reported as:
Least squares mean · CSBMs/week
Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period
CSBMs/weekPlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period1.240 ± 0.3080.815 ± 0.3281.005 ± 0.3091.320 ± 0.314
Statistical analysis
  • Placebo vs LIN Dose A (9 ug or 18 ug) · ANCOVA · p = 0.3461 · Least squares mean difference: -0.425 · 95% CI -1.313 to 0.463ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose B (18 ug or 36 ug) · ANCOVA · p = 0.5892 · Least squares mean difference: -0.235 · 95% CI -1.095 to 0.624ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
  • Placebo vs LIN Dose C (36 ug or 72 ug) · ANCOVA · p = 0.8560 · Least squares mean difference: 0.080 · 95% CI -0.789 to 0.949ANCOVA model was applied with treatment arm groups (linaclotide doses A, B, and C, and placebo) and age group (6 to 11 years of age and 12 to 17 years of age) as factors and baseline value as covariate.
SecondaryChange From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment

Participants recorded the presence of incontinence episodes in daytime daily since pre-treatment period (14-day prior to randomization) in the evening eDiary for participants randomized following protocol amendment #3. The 4-week daytime fecal incontinence was calculated as the mean of non-missing participant scores reported in the evening eDiary during the Treatment Period. Baseline value was the average of values collected 14 days before randomization. Change from Baseline was calculated as the 4-week fecal incontinence daytime symptoms during the treatment period - fecal incontinence daytime symptoms at baseline. A negative change from Baseline indicates improvement. No data is reported for LIN 145 μg as it was an exploratory arm group.

Time frame:
Baseline (14-day prior to randomization) to Week 4
Reported as:
Mean · incontinence episodes
Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment
incontinence episodesPlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)
Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment-0.028 ± 0.081-0.025 ± 0.083-0.009 ± 0.0670.170 ± 0.298

Adverse events

Collected over From first dose of study treatment up to Day 30 after the last dose for serious adverse events (SAEs) and from first dose up to Day 1 after the last dose for other adverse events. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/41 (0%)0/41 (0%)3/41 (7.3%)
LIN Dose A (9 ug or 18 ug)0/36 (0%)1/36 (2.8%)1/36 (2.8%)
LIN Dose B (18 ug or 36 ug)0/41 (0%)0/41 (0%)3/41 (7.3%)
LIN Dose C (36 ug or 72 ug)0/39 (0%)0/39 (0%)10/39 (25.6%)
LIN 145 µg0/16 (0%)1/16 (6.3%)4/16 (25%)
Most frequent serious events
Most frequent serious events
EventPlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µg
VomitingGastrointestinal disorders0/410/360/410/391/16
Suicidal ideationPsychiatric disorders0/411/360/410/390/16
Most frequent other events
Most frequent other events
EventPlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µg
DiarrhoeaGastrointestinal disorders0/411/363/414/392/16
HeadacheNervous system disorders1/411/360/414/390/16
Viral sinusitisInfections and infestations0/410/360/410/391/16
Alanine aminotransferase increasedInvestigations1/410/360/410/391/16
Aspartate aminotransferase increasedInvestigations1/410/360/410/391/16
VomitingGastrointestinal disorders1/411/360/410/391/16
FaecalomaGastrointestinal disorders0/410/360/412/390/16

Baseline characteristics

Safety population included all participants in the randomized population who took at least 1 dose of double-blind study treatment.

Age, Continuous
Age, Continuous(years)PlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µgTotal
Mean10.7 (6 to 17)10.9 (6 to 16)11.0 (6 to 17)11.3 (6 to 17)14.7 (12 to 17)11.3 (6 to 17)
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µgTotal
Female20172523893
Male21191616880
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µgTotal
White3029322911131
Black or African American10798438
Asian000011
American Indian or Alaska Native000101
Multiple100102
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µgTotal
Hispanic or Latino87129440
Not Hispanic or Latino3329293012133
Spontaneous Bowel Movement (SBM) Frequency Rate
Spontaneous Bowel Movement (SBM) Frequency Rate(SBMs/week)PlaceboLIN Dose A (9 ug or 18 ug)LIN Dose B (18 ug or 36 ug)LIN Dose C (36 ug or 72 ug)LIN 145 µgTotal
Mean1.248 (0.00 to 2.90)1.462 (0.00 to 2.90)1.307 (0.00 to 2.90)1.324 (0.00 to 2.90)1.810 (0.00 to 4.83)1.376 (0.00 to 4.83)
08

Study locations

62 sites
  • HealthStar Research, LLC
    Hot Springs, Arkansas 71913, United States
  • Applied Research Center of Arkansas
    Little Rock, Arkansas 72212, United States
  • Advanced Research Center
    Anaheim, California 92805, United States
  • Kindred Medical Institute for Clinical Trials, LLC
    Corona, California 92879, United States
  • WCCT Global, LLC
    Costa Mesa, California 92626, United States
  • Ark Clinical Research
    Long Beach, California 90806, United States
  • ACTCA, Inc
    Los Angeles, California 90017, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90017, United States
  • Orange County Research Institute
    Ontario, California 91762, United States
  • Center for Clinical Trials, LLC
    Paramount, California 90723, United States
  • UCSD Rady Children's Hospital
    San Diego, California 92123, United States
  • University of California at San Francisco
    San Francisco, California 94143, United States
  • Ventura Clinical Trials
    Ventura, California 93003, United States
  • Colorado Springs Health Partners, HCP-Clinical Research, LLC
    Colorado Springs, Colorado 80922, United States
  • Nova Southeastern University
    Fort Lauderdale, Florida 33314, United States
  • Homestead Research Institute
    Homestead, Florida 33030, United States
  • RM Medical Research
    Homestead, Florida 33030, United States
  • Advanced Medical Research Center
    Miami, Florida 33135, United States
  • SCORE Physician Alliance, LLC
    Saint Petersburg, Florida 33710, United States
  • Children's Center for Digestive Health Care LLC
    Atlanta, Georgia 30342, United States
  • Sleepcare Clinical Research Institute
    Stockbridge, Georgia 30281, United States
  • Riley Hospital for Children at Indiana University Health
    Indianapolis, Indiana 46202, United States
  • Heartland Research Associates, LLC
    Wichita, Kansas 67205, United States
  • Kentucky Pediatric/ Adult Research
    Bardstown, Kentucky 40004, United States
  • Kosair Children's Hospital - Pediatric Clinical Research Unit
    Louisville, Kentucky 40202, United States
  • Michael W. Simon, MD, PSC
    Nicholasville, Kentucky 40356, United States
  • Willis-Knighton Physician Network
    Shreveport, Louisiana 71118, United States
  • University of Maryland Children's Hospital
    Baltimore, Maryland 21201, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University Of Minnesota
    Minneapolis, Minnesota 55455, United States
  • GI Associates and Endoscopy Center
    Jackson, Mississippi 39232, United States
  • Craig A. Speigel, MD
    Bridgeton, Missouri 63044, United States
  • Midwest Children Health Research Institute
    Lincoln, Nebraska 68505, United States
  • Midwest Children Health Research Institute
    Lincoln, Nebraska 68516, United States
  • Goryeb Children's Hospital
    Morristown, New Jersey 07962, United States
  • Columbia University Medical Center and Morgan Stanley
    New York, New York 10032, United States
  • Asheboro Research Associates
    Asheboro, North Carolina 27203, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599, United States
  • Capital Pediatrics and Adolescent Center PLLC
    Raleigh, North Carolina 27609, United States
  • Ohio Pediatric Research Association
    Dayton, Ohio 45414, United States
  • IPS Research Company
    Oklahoma City, Oklahoma 73103, United States
  • Pediatric Care Specialists
    Johnstown, Pennsylvania 15904, United States
  • St. Christopher's Hospital for Children
    Philadelphia, Pennsylvania 19134, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Preferred Primary Care Physicians, Inc.
    Pittsburgh, Pennsylvania 15236, United States
  • Frontier Clinical Research, LLC
    Scottdale, Pennsylvania 15683, United States
  • Montgomery Medical Inc.
    Smithfield, Pennsylvania 15478, United States
  • Rhode Island Hospital
    Providence, Rhode Island 02903, United States
  • Coastal Pediatric Research
    Charleston, South Carolina 29414, United States
  • Coastal Pediatrics Associates
    Mount Pleasant, South Carolina 29464, United States
  • Cook Children's Medical Center
    Fort Worth, Texas 76104, United States
  • Texas Children's Hospital/Baylor College Medicine
    Houston, Texas 77030, United States
  • Houston Clinical Research Associates
    Houston, Texas 77090, United States
  • Sun Research Institute
    San Antonio, Texas 78215, United States
  • Southwest Children's Research Associates, P.A.
    San Antonio, Texas 78229, United States
  • ClinPoint Trials
    Waxahachie, Texas 75165, United States
  • Foothill Family Clinic South / J. Lewis Research, Inc.
    Salt Lake City, Utah 84121, United States
  • Pediatric Specialists of Virginia
    Fairfax, Virginia 22031, United States
  • Virginia Tech Carilion School of Medicine Pediatric
    Roanoke, Virginia 24013, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • Stollery Children's Hospital
    Edmonton, Alberta T6G 2B7, Canada
  • Children's Hospital of Western Ontario
    London, Ontario N6A 4G5, Canada
09

References and documents

Study documents

  • Study protocol · May 16, 2017
  • Statistical analysis plan · Jun 28, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02559570
Lead sponsor
Forest Laboratories
Collaborators
Ironwood Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Sep 24, 2015
Start date
Nov 3, 2015
Primary completion
Apr 20, 2018
Completion
May 29, 2018
Results posted
May 14, 2019
Last update
Jun 19, 2019

Study contacts

Taryn Weissman
study director · Allergan, LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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