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)
A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide in Pediatric Participants, Ages 6 to 17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) and of Linaclotide Versus Placebo in Pediatric Participants With Functional Constipation (FC)
2 other identifiers
interventional
438
13 countries
114
Brief Summary
The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (72 μg daily) in comparison with placebo in pediatric participants, 6 to 17 years of age, who fulfill modified Rome III Criteria for child/adolescent FC. The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (145 μg or 290 μg daily) in pediatric participants 7 to 17 years of age, who fulfill the Rome III criteria for child/adolescent IBS and modified Rome III criteria for child/adolescent FC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2019
Longer than P75 for phase_3
114 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2019
CompletedFirst Posted
Study publicly available on registry
July 19, 2019
CompletedStudy Start
First participant enrolled
October 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 20, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
May 29, 2024
CompletedResults Posted
Study results publicly available
November 26, 2024
CompletedNovember 26, 2024
October 1, 2024
4.6 years
July 17, 2019
October 31, 2024
October 31, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Functional Constipation (FC) Participants: Change From Baseline in 12-week SBM (Spontaneous Bowel Movement) Frequency Rate (SBMs/Week) During the Study Intervention Period
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.
Baseline, up to 12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks APS (Abdominal Pain and SBM) + 2 Responder Rate
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.
12 Weeks
Secondary Outcomes (6)
Functional Constipation (FC) Participants: Change From Baseline in 12-week Stool Consistency During the Study Intervention Period
Baseline, up to 12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week SBM Frequency Rate (SBMs/Week) During the Study Intervention Period
Baseline, up to 12 Weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week Abdominal Pain During the Study Intervention Period
Baseline, up to 12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: Change From Baseline in 12-week Stool Consistency During the Study Intervention Period
Baseline, up to 12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks SBM + 2 Responder Rate
12 weeks
- +1 more secondary outcomes
Study Arms (4)
FC Participants: Placebo
EXPERIMENTALPlacebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.
FC Participants: Linaclotide 72 μg
EXPERIMENTALLinaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
IBS-C Participants: Linaclotide 145 μg
EXPERIMENTALLinaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.
IBS-C Participants: Linaclotide 290 μg
EXPERIMENTALLinaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal
Interventions
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)
Eligibility Criteria
You may qualify if:
- Male and female participants must be ages 6 to 17 years (FC participants) or ages 7 to 17 years (IBS-C participants) (inclusive) at the time the participant provides assent for the study and parent/guardian/legally authorized representative (LAR) has provided signed consent;
- Participant weighs ≥18 kg at the time the participant provides assent and the parent/guardian/LAR has provided signed consent;
- Participants who meet the 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, participant meets one or more of the following criteria at least once per week for at least 2 months before the screening visit:
- a. History of retentive posturing or excessive volitional stool retention; b. History of painful or hard BMs; c. History of large diameter stools that may obstruct the toilet; d. Presence of a large fecal mass in the rectum; e. At least 1 episode of fecal incontinence per week
- For IBS-C participants only: Participant meets Rome III criteria for child/adolescent IBS: At least once per week for at least 2 months before the Screening Visit, the participant 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:
- Improvement with defecation;
- Onset associated with a change in frequency of stool;
- Onset associated with a change in form (appearance) of stool;
- For IBS-C participants only: Participant has an average daytime abdominal pain score of ≥ 1 (at least "a tiny bit") during the 14 days before Visit 3;
- Participant is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol- permitted rescue medicine;
- Participant has an average of fewer than 3 SBMs per week during the 14 days before the randomization day and up to the randomization (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day). 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 parent/guardian/LAR or caregiver is compliant with eDiary requirements by completing both the morning and evening assessments for 10 out of the 14 days immediately preceding the Randomization Visit;
- Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Randomization Visit prior to dosing;
- Female participants who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception;
- +3 more criteria
You may not qualify if:
- For FC participants only: Participant meets Rome III criteria for Child/Adolescent 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:
- Improvement with defecation
- Onset associated with a change in frequency of stool
- 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 (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day);
- Participant has a history of non-retentive fecal incontinence;
- Participant has (a) fecal impaction at Visit 2 after failing outpatient clean-out during the Screening Period or (b) fecal impaction at Visit 3;
- Participant has required manual disimpaction any time prior to randomization;
- Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding \[rectal bleeding or heme-positive stool\], iron-deficiency anemia, or any unexplained anemia, or weight loss) and systemic signs of infection or colitis, or any neoplastic process;
- Participant has a history of drug or alcohol abuse;
- Participant has any of the following conditions:
- Celiac disease, or positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy;
- Cystic fibrosis;
- Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to the Screening Visit;
- Down's syndrome or any other chromosomal disorder;
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
- Ironwood Pharmaceuticals, Inc.collaborator
Study Sites (115)
Central Research Associates /ID# 233124
Birmingham, Alabama, 35205, United States
G & L Research, LLC /ID# 233139
Foley, Alabama, 36535, United States
The Center for Clinical Trials Inc. /ID# 232755
Saraland, Alabama, 36571, United States
HealthStar Research of Hot Springs PLLC /ID# 232757
Hot Springs, Arkansas, 71913, United States
Preferred Research Partners /ID# 233023
Little Rock, Arkansas, 72211, United States
Applied Research Center of Arkansas /ID# 233135
Little Rock, Arkansas, 72212-4187, United States
Advanced Research Center /ID# 233121
Anaheim, California, 92805, United States
Alliance Research Institute /ID# 232754
Bell Gardens, California, 90201, United States
Alliance Research Institute Llc /Id# 232637
Canoga Park, California, 91304, United States
Kindred Medical Institute, LLC /ID# 233042
Corona, California, 92879, United States
Center for Clinical Trials LLC /ID# 232781
Paramount, California, 90723, United States
Medical Ctr for Clin Research /ID# 233004
San Diego, California, 92108, United States
Paragon Rx Clinical Inc /ID# 232752
Santa Ana, California, 92703, United States
Lynn Institute of Denver /ID# 233137
Aurora, Colorado, 80012, United States
Children's National Medical Center /ID# 232655
Washington D.C., District of Columbia, 20010-2916, United States
Prohealth Research Center /ID# 232805
Doral, Florida, 33166, United States
Dolphin Medical Research /ID# 232815
Doral, Florida, 33172, United States
Amedica Research Institute Inc /ID# 232809
Hialeah, Florida, 33013, United States
Nemours Children's Health System /ID# 233127
Jacksonville, Florida, 32207, United States
Elite Clinical Research /ID# 232801
Miami, Florida, 33144, United States
My Preferred Research LLC /ID# 233119
Miami, Florida, 33155, United States
South Miami Medical & Research Group Inc. /ID# 232803
Miami, Florida, 33155, United States
Valencia Medical & Research Center /ID# 232813
Miami, Florida, 33165, United States
Advanced Research for Health Improvement /ID# 233161
Naples, Florida, 34102-5430, United States
Pediatric & Adult Research Center /ID# 232819
Orlando, Florida, 32825, United States
Nemours Children's Hospital /ID# 232919
Orlando, Florida, 32827-7884, United States
Oviedo Medical Research /ID# 232830
Oviedo, Florida, 32765, United States
Treken Primary Care /ID# 232796
Atlanta, Georgia, 30315, United States
Children's Healthcare of Atlanta - Ferry Rd /ID# 233015
Atlanta, Georgia, 30342-1605, United States
Children's Ctr Digestive, US /ID# 233070
Atlanta, Georgia, 30342, United States
River Birch Research Alliance /ID# 233122
Blue Ridge, Georgia, 30513, United States
Clinical Research Institute /ID# 232833
Stockbridge, Georgia, 30281, United States
Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 232940
Stockbridge, Georgia, 30281, United States
Clinical Trials Specialist Inc /ID# 232802
Stone Mountain, Georgia, 30083, United States
Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 232800
Union City, Georgia, 30291, United States
Univ Kansas Med Ctr /ID# 232645
Kansas City, Kansas, 66160, United States
Alliance for Multispecialty Research LLC /ID# 232681
Newton, Kansas, 67114, United States
Michael W. Simon, MD, PSC /ID# 232966
Lexington, Kentucky, 40517, United States
Meridian Research - Baton Rouge /ID# 232954
Baton Rouge, Louisiana, 70806-7631, United States
Virgo Carter Pediatrics /ID# 232693
Silver Spring, Maryland, 20910, United States
MNGI Digestive Health, P. A. /ID# 232920
Minneapolis, Minnesota, 55413-2195, United States
GI associates and Endoscopy Ce /ID# 233123
Flowood, Mississippi, 39232, United States
David M. Headley, MD, P.A. /ID# 233153
Port Gibson, Mississippi, 39150-2024, United States
Private Practice - Dr. Craig Spiegel /ID# 232707
Bridgeton, Missouri, 63044, United States
Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 232783
East Orange, New Jersey, 07018, United States
University of New Mexico /ID# 233011
Albuquerque, New Mexico, 87102-4517, United States
Columbia Univ Medical Center /ID# 233094
New York, New York, 10032-3725, United States
The Children's Hospital at Montefiore /ID# 232638
The Bronx, New York, 10467, United States
Advantage Clinical Trials /ID# 233117
The Bronx, New York, 10468, United States
East Carolina University - Brody School of Medicine /ID# 233062
Greenville, North Carolina, 27834, United States
PMG Research of Piedmont Healthcare-Statesville /ID# 233162
Statesville, North Carolina, 28625, United States
Univ Oklahoma HSC /ID# 233067
Oklahoma City, Oklahoma, 73104, United States
IPS Research Company /ID# 233081
Oklahoma City, Oklahoma, 73106, United States
Frontier Clinical Research, LLC - Scottdale /ID# 233129
Scottdale, Pennsylvania, 15683, United States
Frontier Clinical Research /ID# 233116
Smithfield, Pennsylvania, 15478, United States
Rhode Island Hospital /ID# 233112
Providence, Rhode Island, 02903, United States
Coastal Pediatric Research - West Ashley B /ID# 232816
Charleston, South Carolina, 29414, United States
Coastal Pediatric Research - Summerville /ID# 232814
Summerville, South Carolina, 29486, United States
The Jackson Clinic, PA /ID# 232998
Jackson, Tennessee, 38305, United States
Accellacare of Knoxville /ID# 232663
Jefferson City, Tennessee, 37760, United States
Monroe-Carell Jr. Children's Hospital at Vanderbilt /ID# 232659
Nashville, Tennessee, 37232, United States
Oak Cliff Research Company LLC /ID# 232729
Dallas, Texas, 75243, United States
Cook Children's Med. Center /ID# 233066
Fort Worth, Texas, 76104, United States
Valley Institute of Research /ID# 232674
Harlingen, Texas, 78550, United States
Vilo Research Group Inc /ID# 233155
Houston, Texas, 77017-2337, United States
Cullen Research /ID# 232726
Houston, Texas, 77051, United States
Synergy Group US LLC /ID# 232669
Houston, Texas, 77061, United States
Pioneer Research Solutions - Houston /ID# 233006
Houston, Texas, 77099-4307, United States
Synergy Group US LLC /ID# 232670
Missouri City, Texas, 77459, United States
AIM Trials /ID# 232934
Plano, Texas, 75093, United States
Sun Research Institute /ID# 233005
San Antonio, Texas, 78215, United States
ClinPoint Trials /ID# 232978
Waxahachie, Texas, 75165-1430, United States
Chrysalis Clinical Research /ID# 232690
St. George, Utah, 84790, United States
Office of Maria Ona /ID# 232700
Franklin, Virginia, 23851, United States
Health Research of Hampton Roads, Inc. (HRHR) /ID# 233056
Newport News, Virginia, 23606, United States
Clinical Research Partners, LLC /ID# 233026
Richmond, Virginia, 23220-4459, United States
Carilion Medical Center /ID# 232999
Roanoke, Virginia, 24014, United States
Duplicate_Multicare Institute for Research and Innovation /ID# 233010
Tacoma, Washington, 98405, United States
Marshall University Medical Center /ID# 232952
Huntington, West Virginia, 25701-3656, United States
Duplicate_UZ Brussel /ID# 232875
Brussels, 1090, Belgium
University Hospital Plovdiv /ID# 232775
Tsentar, Plovdiv, 4001, Bulgaria
UMHAT Kanev /ID# 233102
Ruse, Smolyan, 7002, Bulgaria
Medical center 1 Sevlievo /ID# 232915
Sevlievo, Smolyan, 5400, Bulgaria
MHATSv.Ivan Rilski /ID# 232831
Kozloduy, 3320, Bulgaria
University of Alberta Hospital /ID# 233147
Edmonton, Alberta, T6G 2B7, Canada
London Health Sciences Center- University Hospital /ID# 233068
London, Ontario, N6A 5W9, Canada
Duplicate_SKDS Research Inc. /ID# 233000
Newmarket, Ontario, L3Y 5G8, Canada
Bluewater Clinical Research Group Inc /ID# 232772
Sarnia, Ontario, N7T 4X3, Canada
Stouffville Medical Centre /ID# 232774
Stouffville, Ontario, L4A 1H2, Canada
Merelahe Family Doctors Centre /ID# 232881
Tallinn, Raplamaa, 10617, Estonia
Kliiniliste Uuringute Keskus /ID# 232883
Tartu, Raplamaa, 50410, Estonia
Al Mare Perearstikeskus /ID# 232879
Harjumaa, 10617, Estonia
Duplicate_Klinikum Kassel /ID# 233029
Kassel, Hesse, 34125, Germany
Schneider Children's Medical Center /ID# 233064
Petah Tikva, Central District, 4920235, Israel
Duplicate_Rambam Health Care Campus Ruth Rappaport Children's Hospital /ID# 232892
Haifa, H_efa, 31096, Israel
Shaare Zedek Medical Center /ID# 233092
Jerusalem, Jerusalem, 91031, Israel
Hadassah Hebrew University Hospital - Ein Kerem /ID# 232865
Jerusalem, Jerusalem, 91120, Israel
The Baruch Padeh Medical Center Poriya /ID# 232889
Tiberias, Northern District, 15208, Israel
The Edith Wolfson Medical Center /ID# 233134
Ashkelon, Southern District, 5822000, Israel
The Chaim Sheba Medical Center /ID# 232986
Ramat Gan, Tel Aviv, 5265601, Israel
Sant?Andrea University Hospital /ID# 232825
Rome, 00189, Italy
Duplicate_Academisch Medisch Centrum /ID# 232895
Amsterdam, North Holland, 1105 AZ, Netherlands
Maasstad Ziekenhuis /ID# 233003
Rotterdam, South Holland, 3079 DZ, Netherlands
Isala /ID# 233031
Zwolle, South Holland, 8025 AB, Netherlands
Szpital Uniwersytecki Nr 1 im. dr Antoniego Jurasza /ID# 232898
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094, Poland
Klinika Pediatrii Gastroenterologii Alergologii i Zywienia Dzieci GUM /ID# 232900
Gdansk, Kuyavian-Pomeranian Voivodeship, 80-803, Poland
Poradnia Gastroenterologiczna /ID# 232899
Olsztyn, Kuyavian-Pomeranian Voivodeship, 10-561, Poland
Korczowski Bartosz Gabinet Lekarski /ID# 232821
Rzeszow, Kuyavian-Pomeranian Voivodeship, 35-302, Poland
San Juan Bautista School of Medicine /ID# 232913
Caguas, 726, Puerto Rico
Instituto Hispalense Pediatria /ID# 232793
Seville, 41014, Spain
Kharkiv Regional Childrens Clinical Hospital Gastroent. Centre Kharkiv Natl. Me /ID# 232867
Kharkiv, Cherkasy Oblast, 61093, Ukraine
Municipal Nonprofit Enterprise Lviv City Children's Clinical Hospital /ID# 232851
Lviv, Cherkasy Oblast, 79059, Ukraine
Vinnytsya National Medical University Departement of Pediatrics No.1 /ID# 232890
Vinnytsia, Cherkasy Oblast, 21029, Ukraine
Communal Nonprofit Enterprise City Childrens Clinical Hospital 6 of Dnipro C /ID# 232863
Dnipro, 49064, Ukraine
William Harvey Hospital /ID# 232806
Ashford, Kent, TN24 0LZ, United Kingdom
Related Publications (1)
Di Lorenzo C, Khlevner J, Rodriguez-Araujo G, Xie W, Huh SY, Ando M, Hyams JS, Nurko S, Benninga MA, Simon M, Hewson ME, Saps M. Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Gastroenterol Hepatol. 2024 Mar;9(3):238-250. doi: 10.1016/S2468-1253(23)00398-9. Epub 2024 Jan 8.
PMID: 38211604DERIVED
MeSH Terms
Interventions
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2019
First Posted
July 19, 2019
Study Start
October 1, 2019
Primary Completion
May 20, 2024
Study Completion
May 29, 2024
Last Updated
November 26, 2024
Results First Posted
November 26, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
- Access Criteria
- Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.