Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Sequential, Ascending, Multidose Study to Evaluate the Safety and Efficacy of Linaclotide in Pediatric Participants (Age 2 to 5 Years) with Functional Constipation
Summary
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EudraCT number |
2019-002126-75 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Nov 2021
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First version publication date |
04 Nov 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LIN-MD-67
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04110145 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Allergan
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Sponsor organisation address |
1st Floor, Marlow International, The Parkway, Marlow Buckinghamshire, United Kingdom, SL7 1YL
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Public contact |
Therapeutic Area, Head, Allergan, 001 714-246-4500, IR-CTRegistration@Allergan.com
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Scientific contact |
Therapeutic Area, Head, Allergan, 001 714-246-4500, IR-CTRegistration@Allergan.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000927-PIP01-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Apr 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study was to evaluate the dose response, safety, and efficacy of linaclotide when compared with placebo in pediatric participants, 2 to 5 years of age, with Functional Constipation.
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Oct 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 35
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Worldwide total number of subjects |
35
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
35
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participants were randomized in a 3:1 ratio to receive ascending dose of linaclotide Cohorts 1-3 (18/36/72 μg) to determine the highest dose to be safe or placebo and in a 5:1 ratio for the Final Cohort (72 μg) safe dose or placebo. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Double-Blind Treatment Period (4 weeks)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1 (Linaclotide 18 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 18 microgram (μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 18 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Cohort 2 (Linaclotide 36 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Cohort 3 (Linaclotide 72 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Final Cohort (Linaclotide 72 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Placebo Pooled | ||||||||||||||||||||||||||||||
Arm description |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matching linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal).
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Period 2
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Period 2 title |
Post-treatment Period (1 week)
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1 (Linaclotide 18 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 18 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 18 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Cohort 2 (Linaclotide 36 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal)
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Arm title
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Cohort 3 (Linaclotide 72 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Final Cohort (Linaclotide 72 μg) | ||||||||||||||||||||||||||||||
Arm description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal).
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Arm title
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Placebo Pooled | ||||||||||||||||||||||||||||||
Arm description |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matching linaclotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal).
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 1 participant in the Cohort 3 (Linaclotide 72 μg) arm group completed Period 1 but did not participate in Period 2. |
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 1 (Linaclotide 18 μg)
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Reporting group description |
Linaclotide 18 microgram (μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2 (Linaclotide 36 μg)
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Reporting group description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 3 (Linaclotide 72 μg)
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Reporting group description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Final Cohort (Linaclotide 72 μg)
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Reporting group description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Pooled
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Reporting group description |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1 (Linaclotide 18 μg)
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Reporting group description |
Linaclotide 18 microgram (μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Cohort 2 (Linaclotide 36 μg)
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Reporting group description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Cohort 3 (Linaclotide 72 μg)
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Reporting group description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Final Cohort (Linaclotide 72 μg)
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Reporting group description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Placebo Pooled
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Reporting group description |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. | ||
Reporting group title |
Cohort 1 (Linaclotide 18 μg)
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Reporting group description |
Linaclotide 18 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Cohort 2 (Linaclotide 36 μg)
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Reporting group description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Cohort 3 (Linaclotide 72 μg)
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Reporting group description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Final Cohort (Linaclotide 72 μg)
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Reporting group description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||
Reporting group title |
Placebo Pooled
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Reporting group description |
Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. |
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End point title |
Change from Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/week) During the Study Intervention Period of Each Cohort [1] | ||||||||||||||||||||||||||||||||||||
End point description |
A SBM was defined as a bowel movement (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. Each day caregiver recorded the number of SBMs in the last 24 hours in an electronic diary(eDiary). 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. Modified-intent-to-treat (mITT) Population included all Randomized Population who received at least 1 dose of double-blind study intervention and who had at least 1 postbaseline entry on BM characteristic assessments that determine occurrences of SBMs.
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End point type |
Primary
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End point timeframe |
Baseline (14 days prior to randomization) to Day 29
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in 4-week Stool Consistency Reported by the Caregiver During the Study Intervention Period of Each Cohort [2] | ||||||||||||||||||||||||||||||||||||
End point description |
The caregiver rated and recorded in an eDiary the consistency of the stool for each bowel movement using the Bristol Stool Form 7-point scale where: 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; 7=Watery, no solid pieces. Entirely liquid. Baseline value was based on values collected 14 days before randomization up to randomization. A participant’s stool consistency score for the treatment period was the average of the nonmissing consistency scores from the BMs recorded by the caregiver during the 4-week treatment period. mITT Population. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Primary
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End point timeframe |
Baseline (14 days prior to randomization) to Day 29
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in 4-week Straining Reported by the Caregiver During the Study Intervention Period of Each Cohort [3] | ||||||||||||||||||||||||||||||||||||
End point description |
The caregiver rated and recorded in an eDiary the amount of straining they observed when the child passed the BM (1=Not at all; 2=Yes a little; 3=Yes a lot; 99=I don’t know). Baseline value was based on values collected 14 days before randomization up to randomization. A participant’s straining score for the treatment period was the average of the nonmissing straining scores from the BMs recorded by the caregiver during the 4-week treatment period. A negative change from Baseline indicates improvement. mITT Population included all Randomized Population who received at least 1 dose of double-blind study intervention and who had at least 1 postbaseline entry on BM characteristic assessments that determine occurrences of SBMs. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Primary
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End point timeframe |
Baseline (14 days prior to randomization) to Day 29
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Days with Fecal Incontinence During the Study Intervention Period (for Participants who have Acquired Toileting Skills During the Daytime and Nighttime or Acquired Toileting Skills During Daytime Only) Within Each Cohort [4] | ||||||||||||||||||||||||
End point description |
Each day the caregiver recorded in an eDiary if the child had a bowel movement accident (Yes; No; I don’t know). The percentage of days with fecal incontinence for the treatment period was the average of the nonmissing incidences of fecal incontinence recorded by the caregiver during the 4-week treatment period. mITT Population included all Randomized Population who received at least 1 dose of double-blind study intervention and who had at least 1 postbaseline entry on BM characteristic assessments that determine occurrences of SBMs. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Primary
|
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End point timeframe |
29 days
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [5] | ||||||||||||||||||||||||||||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease. A serious adverse event (SAE) is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that begins or worsens after receiving study drug. Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind study intervention.
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End point type |
Primary
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End point timeframe |
First dose of study drug intervention to within 1 week of last dose (Up to 45 days)
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses are reported for this endpoint. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
First dose of study drug intervention to within 1 week of last dose (Up to 45 days)
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Adverse event reporting additional description |
All-Cause Mortality: All randomized participants. Serious Adverse Events and Other Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind study intervention.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Cohort 2 (Linaclotide 36 μg)
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Reporting group description |
Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 1 (Linaclotide 18 μg)
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Reporting group description |
Linaclotide 18 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Final Cohort (Linaclotide 72 μg)
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Reporting group description |
Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Pooled
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Reporting group description |
Matching placebo once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 3 (Linaclotide 72 μg)
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Reporting group description |
Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 May 2020 |
The purpose of Global Protocol Amendment 1 was to include an assessment of modified Rome III criteria at the end of treatment as an ‘other’ efficacy endpoint, to include a fecal impaction assessment prior to randomization and dosing, and to provide additional clarification and updates to the LIN-MD-67 protocol (dated 01 May 2019); European Union (EU) sites would not be included in the study; Information was provided on study conduct during the novel coronavirus pandemic; Appendix: Liver Safety was added. |
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Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |