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) (LINZESS)

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)

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation; Functional Constipation
• Intervention / Treatment: Drug: Placebo; Drug: Linaclotide

• Study Type: Interventional
• Enrollment (Actual): 438
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Duplicate_UZ Brussel /ID# 232875
• Bulgaria
  • Kozloduy, Bulgaria, 3320
    • MHATSv.Ivan Rilski /ID# 232831
  • Plovdiv
    • Tsentar, Plovdiv, Bulgaria, 4001
      • University Hospital Plovdiv /ID# 232775
  • Smolyan
    • Ruse, Smolyan, Bulgaria, 7002
      • UMHAT Kanev /ID# 233102
    • Sevlievo, Smolyan, Bulgaria, 5400
      • Medical center 1 Sevlievo /ID# 232915
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital /ID# 233147
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Center- University Hospital /ID# 233068
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Duplicate_SKDS Research Inc. /ID# 233000
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group Inc /ID# 232772
    • Stouffville, Ontario, Canada, L4A 1H2
      • Stouffville Medical Centre /ID# 232774
• Estonia
  • Harjumaa, Estonia, 10617
    • Al Mare Perearstikeskus /ID# 232879
  • Raplamaa
    • Tallinn, Raplamaa, Estonia, 10617
      • Merelahe Family Doctors Centre /ID# 232881
    • Tartu, Raplamaa, Estonia, 50410
      • Kliiniliste Uuringute Keskus /ID# 232883
• Germany
  • Hessen
    • Kassel, Hessen, Germany, 34125
      • Duplicate_Klinikum Kassel /ID# 233029
• Israel
  • H_efa
    • Haifa, H_efa, Israel, 31096
      • Duplicate_Rambam Health Care Campus Ruth Rappaport Children's Hospital /ID# 232892
  • HaDarom
    • Ashkelon, HaDarom, Israel, 5822000
      • The Edith Wolfson Medical Center /ID# 233134
  • HaMerkaz
    • Petah Tikva, HaMerkaz, Israel, 4920235
      • Schneider Children's Medical Center /ID# 233064
  • HaTsafon
    • Tiberias, HaTsafon, Israel, 15208
      • The Baruch Padeh Medical Center Poriya /ID# 232889
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 232986
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91031
      • Shaare Zedek Medical Center /ID# 233092
    • Jerusalem, Yerushalayim, Israel, 91120
      • Hadassah Hebrew University Hospital - Ein Kerem /ID# 232865
• Italy
  • Rome, Italy, 00189
    • Sant?Andrea University Hospital /ID# 232825
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Duplicate_Academisch Medisch Centrum /ID# 232895
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
      • Maasstad Ziekenhuis /ID# 233003
    • Zwolle, Zuid-Holland, Netherlands, 8025 AB
      • Isala /ID# 233031
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Szpital Uniwersytecki Nr 1 im. dr Antoniego Jurasza /ID# 232898
    • Gdansk, Kujawsko-pomorskie, Poland, 80-803
      • Klinika Pediatrii Gastroenterologii Alergologii i Zywienia Dzieci GUM /ID# 232900
    • Olsztyn, Kujawsko-pomorskie, Poland, 10-561
      • Poradnia Gastroenterologiczna /ID# 232899
    • Rzeszow, Kujawsko-pomorskie, Poland, 35-302
      • Korczowski Bartosz Gabinet Lekarski /ID# 232821
• Puerto Rico
  • Caguas, Puerto Rico, 726
    • San Juan Bautista School of Medicine /ID# 232913
• Spain
  • Sevilla, Spain, 41014
    • Instituto Hispalense Pediatria /ID# 232793
• Ukraine
  • Dnipro, Ukraine, 49064
    • Communal Nonprofit Enterprise City Childrens Clinical Hospital 6 of Dnipro C /ID# 232863
  • Cherkaska Oblast
    • Kharkiv, Cherkaska Oblast, Ukraine, 61093
      • Kharkiv Regional Childrens Clinical Hospital Gastroent. Centre Kharkiv Natl. Me /ID# 232867
    • Lviv, Cherkaska Oblast, Ukraine, 79059
      • Municipal Nonprofit Enterprise Lviv City Children's Clinical Hospital /ID# 232851
    • Vinnytsia, Cherkaska Oblast, Ukraine, 21029
      • Vinnytsya National Medical University Departement of Pediatrics No.1 /ID# 232890
• United Kingdom
  • Kent
    • Ashford, Kent, United Kingdom, TN24 0LZ
      • William Harvey Hospital /ID# 232806
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates /ID# 233124
    • Foley, Alabama, United States, 36535
      • G & L Research, LLC /ID# 233139
    • Saraland, Alabama, United States, 36571
      • The Center for Clinical Trials Inc. /ID# 232755
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research of Hot Springs PLLC /ID# 232757
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners /ID# 233023
    • Little Rock, Arkansas, United States, 72212-4187
      • Applied Research Center of Arkansas /ID# 233135
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center /ID# 233121
    • Bell Gardens, California, United States, 90201
      • Alliance Research Institute /ID# 232754
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute Llc /Id# 232637
    • Corona, California, United States, 92879
      • Kindred Medical Institute, LLC /ID# 233042
    • Paramount, California, United States, 90723
      • Center for Clinical Trials LLC /ID# 232781
    • San Diego, California, United States, 92108
      • Medical Ctr for Clin Research /ID# 233004
    • Santa Ana, California, United States, 92703
      • Paragon Rx Clinical Inc /ID# 232752
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Lynn Institute of Denver /ID# 233137
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2916
      • Children's National Medical Center /ID# 232655
  • Florida
    • Doral, Florida, United States, 33166
      • Prohealth Research Center /ID# 232805
    • Doral, Florida, United States, 33172
      • Dolphin Medical Research /ID# 232815
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute Inc /ID# 232809
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System /ID# 233127
    • Miami, Florida, United States, 33144
      • Elite Clinical Research /ID# 232801
    • Miami, Florida, United States, 33155
      • My Preferred Research LLC /ID# 233119
    • Miami, Florida, United States, 33155
      • South Miami Medical & Research Group Inc. /ID# 232803
    • Miami, Florida, United States, 33165
      • Valencia Medical & Research Center /ID# 232813
    • Naples, Florida, United States, 34102-5430
      • Advanced Research for Health Improvement /ID# 233161
    • Orlando, Florida, United States, 32825
      • Pediatric & Adult Research Center /ID# 232819
    • Orlando, Florida, United States, 32827-7884
      • Nemours Children's Hospital /ID# 232919
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research /ID# 232830
  • Georgia
    • Atlanta, Georgia, United States, 30315
      • Treken Primary Care /ID# 232796
    • Atlanta, Georgia, United States, 30342-1605
      • Children's Healthcare of Atlanta - Ferry Rd /ID# 233015
    • Atlanta, Georgia, United States, 30342
      • Children's Ctr Digestive, US /ID# 233070
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance /ID# 233122
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute /ID# 232833
    • Stockbridge, Georgia, United States, 30281
      • Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 232940
    • Stone Mountain, Georgia, United States, 30083
      • Clinical Trials Specialist Inc /ID# 232802
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 232800
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Univ Kansas Med Ctr /ID# 232645
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research LLC /ID# 232681
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Michael W. Simon, MD, PSC /ID# 232966
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806-7631
      • Meridian Research - Baton Rouge /ID# 232954
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Virgo Carter Pediatrics /ID# 232693
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413-2195
      • MNGI Digestive Health, P. A. /ID# 232920
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • GI associates and Endoscopy Ce /ID# 233123
    • Port Gibson, Mississippi, United States, 39150-2024
      • David M. Headley, MD, P.A. /ID# 233153
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Private Practice - Dr. Craig Spiegel /ID# 232707
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 232783
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102-4517
      • University of New Mexico /ID# 233011
  • New York
    • Bronx, New York, United States, 10467
      • The Children's Hospital at Montefiore /ID# 232638
    • Bronx, New York, United States, 10468
      • Advantage Clinical Trials /ID# 233117
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 233094
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University - Brody School of Medicine /ID# 233062
    • Statesville, North Carolina, United States, 28625
      • PMG Research of Piedmont Healthcare-Statesville /ID# 233162
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Univ Oklahoma HSC /ID# 233067
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company /ID# 233081
  • Pennsylvania
    • Scottdale, Pennsylvania, United States, 15683
      • Frontier Clinical Research, LLC - Scottdale /ID# 233129
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research /ID# 233116
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital /ID# 233112
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research - West Ashley B /ID# 232816
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatric Research - Summerville /ID# 232814
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic, PA /ID# 232998
    • Jefferson City, Tennessee, United States, 37760
      • Accellacare of Knoxville /ID# 232663
    • Nashville, Tennessee, United States, 37232
      • Monroe-Carell Jr. Children's Hospital at Vanderbilt /ID# 232659
  • Texas
    • Dallas, Texas, United States, 75243
      • Oak Cliff Research Company LLC /ID# 232729
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Med. Center /ID# 233066
    • Harlingen, Texas, United States, 78550
      • Valley Institute of Research /ID# 232674
    • Houston, Texas, United States, 77017-2337
      • Vilo Research Group Inc /ID# 233155
    • Houston, Texas, United States, 77051
      • Cullen Research /ID# 232726
    • Houston, Texas, United States, 77061
      • Synergy Group US LLC /ID# 232669
    • Houston, Texas, United States, 77099-4307
      • Pioneer Research Solutions - Houston /ID# 233006
    • Missouri City, Texas, United States, 77459
      • Synergy Group US LLC /ID# 232670
    • Plano, Texas, United States, 75093
      • AIM Trials /ID# 232934
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute /ID# 233005
    • Waxahachie, Texas, United States, 75165-1430
      • ClinPoint Trials /ID# 232978
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research /ID# 232690
  • Virginia
    • Franklin, Virginia, United States, 23851
      • Office of Maria Ona /ID# 232700
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc. (HRHR) /ID# 233056
    • Richmond, Virginia, United States, 23220-4459
      • Clinical Research Partners, LLC /ID# 233026
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center /ID# 232999
  • Washington
    • Tacoma, Washington, United States, 98405
      • Duplicate_Multicare Institute for Research and Innovation /ID# 233010
  • West Virginia
    • Huntington, West Virginia, United States, 25701-3656
      • Marshall University Medical Center /ID# 232952

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

  1. Improvement with defecation;
  2. Onset associated with a change in frequency of stool;
  3. 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;
• Participant must provide written or verbal informed assent and the parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures;
• Participant is able to read and/or understand the assessments in the eDiary device. If the participant is 6 to 11 years of age (FC participants) or 7 to 11 years of age (IBS-C participants) and does not meet this criterion, the interviewer-administered version of the eDiary must be used and the parent/guardian/LAR or caregiver who will be administering the interviewer-administered version of the eDiary must undergo training;
• Participant must have acquired toilet training skills.

Exclusion Criteria:

• 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:

  1. Improvement with defecation
  2. Onset associated with a change in frequency of stool
  3. 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 clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), or clinical laboratory test as determined by the investigator based on consideration of whether the finding could represent a safety concern or a condition that would be exclusionary, could prevent the participant from performing any protocol assessments, or could confound study assessments;
• Participant has a history of drug or alcohol abuse;

• Participant has any of the following conditions:

  1. Celiac disease, or positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy;
  2. Cystic fibrosis;
  3. 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;
  4. Down's syndrome or any other chromosomal disorder;
  5. Active anal fissure (Note: History of anal fissure is not an exclusion);
  6. Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displaced anus);
  7. Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceral myopathies, visceral neuropathies);
  8. Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma);
  9. Lead toxicity, hypercalcemia;
  10. Neurodevelopmental disabilities (early-onset, chronic disorders that share the essential feature of a predominant disturbance in the acquisition of cognitive, motor, language, or social skills, which has a significant and continuing impact on the developmental progress of an individual) producing a cognitive delay that precludes comprehension and completion of the daily eDiary (Electronic handheld device) or other study-related questionnaires (Note: Participants are excluded if the person who will be completing the daily eDiary or other study-related questionnaires meets this criterion);
  11. Inflammatory bowel disease;
  12. Childhood functional abdominal pain syndrome;
  13. Childhood functional abdominal pain;
  14. Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study;
  15. Lactose intolerance that is associated with abdominal pain or discomfort and could confound the assessments in this study;
  16. History of cancer other than treated basal cell carcinoma of the skin; (Note: Participants with a history of cancer are allowed provided that the malignancy has been in a complete remission for at least 5 years before the Randomization Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment);
  17. History of diabetic neuropathy.
• Participant has an acute or chronic condition that, in the investigator's opinion, would limit the participants' ability to complete or participate in this clinical study;
• Participant has a known or suspected mechanical bowel obstruction or pseudoobstruction;
• Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class.

• Participant has had surgery that meets any of the following criteria:

  1. Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit;
  2. Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit;
  3. An appendectomy or cholecystectomy during the 60 days before the Screening Visit;
  4. Other major surgery during the 30 days before the Screening Visit;
• Participant used a protocol-specified prohibited medicine before the start of the Preintervention Period or failed to meet the stable-dose requirements of certain medications;
• Participant used rescue medication on the calendar day before the Randomization Visit and on the day of the Randomization Visit until randomized;
• Participant received a study intervention during the 30 days before the Screening Visit or is planning to receive a study intervention (other than that administered during this study);
• Participant has been randomized into any clinical study in which linaclotide was a study intervention.
• The participant has a condition or is in a situation; which, in the investigator's opinion, may put the participant at significant risk, may confound the study results ,or may interfere significantly with the participant's participation in the study;
• Participants who have positive urine drug screen results for cocaine, barbiturates, opiates, or cannabinoids will be excluded from study participation;
• Female participants who are currently pregnant or nursing, or plan to become pregnant or nurse during the clinical study;
• Participant's parent/guardian/LAR or caregiver has been directly or indirectly involved in the conduct and administration of this study as an investigator, study coordinator, or other study staff member. In addition, any participant, parent/guardian/LAR or caregiver who has a first-degree family member, significant other, or relative residing with him/her directly or indirectly who is involved in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FC Participants: Placebo; Placebo single dose, once daily at approximately the same time each day, 30 minutes before any meal.	Drug: Placebo; Matching placebo
Experimental: FC Participants: Linaclotide 72 μg; Linaclotide 72 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	Drug: Linaclotide; Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)
Experimental: IBS-C Participants: Linaclotide 145 μg; Linaclotide 145 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal.	Drug: Linaclotide; Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)
Experimental: IBS-C Participants: Linaclotide 290 μg; Linaclotide 290 μg single dose, once daily at approximately the same time each day, 30 minutes before any meal	Drug: Linaclotide; Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Constipation (FC) Participants: Change From Baseline in 12-week Stool Consistency During the Study Intervention Period	Stool consistency was measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal pediatric Bristol Stool Form Scale (p-BSFS): Type 1: Looks like small hard lumps or balls, like pebbles; Type 2: Looks like fat sausage shape but lumpy and hard; Type 3: Looks like a sausage but with cracks on it; Type 4: Looks like a sausage or snake, smooth and soft; Type 5: Looks like chicken nuggets, soft smooth blobs; Type 6: Looks like oatmeal, fluffy mushy pieces; Type 7: Looks like a milkshake, watery. A participant's p-BSFS score for the study intervention period was the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.	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	An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) were measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device. A participant's SBMs/week for the study intervention period was the average of the non-missing SBMs/week reported by the participant during the 12-week study intervention period.	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	Assessments of abdominal pain were measured twice daily, once in the morning and once in the evening eDiary, using a 5-point scale where a score of 0 indicates no abdominal pain scores and a score of 4 indicates a lot of abdominal pain. Assessments of abdominal pain were measured using a 5-point scale where '0' indicates no abdominal pain and '4' indicates a lot of abdominal pain. The participant's abdominal pain score was derived as the mean of the non-missing morning and evening abdominal pain scores during the specified period.	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	Stool consistency was measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery. A participant's p-BSFS score for the study intervention period was the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.	Baseline, up to 12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks SBM + 2 Responder Rate	A 6/12 weeks SBM + 2 responder is a participant that meets the weekly SBM + 2 responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly SBM +2 responder is a participant who has an increase of at least 2 in the SBM weekly rate from baseline, Assessments of BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) were measured by using an eDiary completed twice daily (morning and evening). Responder rate is presented as the percentage of participants who were 6/12 weeks SBM + 2 responders.	12 weeks
Irritable Bowel Syndrome With Constipation (IBS-C) Participants: 6/12 Weeks Abdominal Pain Responder	A 6/12 weeks abdominal pain responder is a participant that meets the weekly abdominal pain responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly abdominal pain responder is a participant who has a decrease of at least 30% in the mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain were measured by using an eDiary completed twice daily (morning and evening) and were measured using a 5-point scale where '0' indicates no abdominal pain and '4' indicates a lot of abdominal pain. The participant's abdominal pain score was derived as the mean of the non-missing abdominal pain scores during the specified period. Responder rate is presented as the percentage of participants who were 6/12 weeks abdominal pain responders.	12 Weeks

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): May 20, 2024
• Study Completion (Actual): May 29, 2024

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Functional constipation in children; Irritable Bowel Syndrome with Constipation; LINZESS
• Additional Relevant MeSH Terms: Pathologic Processes; Signs and Symptoms, Digestive; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Irritable Bowel Syndrome; Syndrome; Constipation; Guanylyl Cyclase C Agonists; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Activators; Linaclotide
• Other Study ID Numbers: LIN-MD-64; 2019-001500-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing 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/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes