Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C

A Phase 3, Open-label, Long-term Safety Study of Oral Linaclotide Administered to Pediatric Participants With Functional Constipation (FC) or Irritable Bowel Syndrome With Constipation (IBS-C)

LIN-MD-66 is a Phase 3 open-label study with 24 weeks (Functional Constipation participants) or 52 weeks (Irritable bowel syndrome with constipation participants) of linaclotide exposure that will enroll pediatric participants (6-17 years of age) with FC or IBS-C who completed study intervention in studies LIN-MD-62, LIN-MD-63, orLIN-MD-64 based on the individual study criteria.

Study Overview

• Status: Enrolling by invitation
• Conditions: Irritable Bowel Syndrome With Constipation; Functional Constipation
• Intervention / Treatment: Drug: Irritable Bowel Syndrome with Constipation (IBS-C) participants (LIN-MD-63 completers); Drug: Functional Constipation (FC) participants (LIN-MD-62 and LIN-MD-64 completers)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Center- University Hospital /ID# 234309
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group Inc /ID# 234618
    • Stouffville, Ontario, Canada, L4A 1H2
      • Stouffville Medical Centre /ID# 234619
• Israel
  • HaTsafon
    • Tiberias, HaTsafon, Israel, 15208
      • The Baruch Padeh Medical Center Poriya /ID# 234768
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 236760
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Hadassah Hebrew University Hospital - Ein Kerem /ID# 234735
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum /ID# 237116
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates /ID# 237953
    • Foley, Alabama, United States, 36535
      • G & L Research, LLC /ID# 238093
    • Saraland, Alabama, United States, 36571
      • The Center for Clinical Trials Inc. /ID# 234605
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research of Hot Springs PLLC /ID# 234608
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners /ID# 237109
    • Little Rock, Arkansas, United States, 72212-4187
      • Applied Research Center of Arkansas /ID# 238069
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center /ID# 237960
    • Corona, California, United States, 92879
      • Kindred Medical Institute, LLC /ID# 237367
    • Paramount, California, United States, 90723
      • Center for Clinical Trials LLC /ID# 234629
    • San Diego, California, United States, 92108
      • Medical Ctr for Clin Research /ID# 236911
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Lynn Institute of Denver /ID# 238086
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2916
      • Children's National Medical Center /ID# 234417
  • Florida
    • Doral, Florida, United States, 33166
      • Prohealth Research Center /ID# 234659
    • Doral, Florida, United States, 33172
      • Dolphin Medical Research /ID# 234676
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute Inc /ID# 234666
    • Jacksonville, Florida, United States, 32207
      • Nemours Childrens Specialty Care /ID# 237991
    • Miami, Florida, United States, 33144
      • Elite Clinical Research /ID# 234651
    • Miami, Florida, United States, 33155
      • South Miami Medical & Research Group Inc. /ID# 234654
    • Miami, Florida, United States, 33165
      • Valencia Medical & Research Center /ID# 234671
    • Miami, Florida, United States, 33155
      • My Preferred Research LLC /ID# 237943
    • Naples, Florida, United States, 34102-5430
      • Advanced Research for Health Improvement /ID# 238253
    • Orlando, Florida, United States, 32825
      • Pediatric & Adult Research Center /ID# 234681
    • Orlando, Florida, United States, 32827-7884
      • Nemours Children's Hospital /ID# 234429
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research /ID# 234692
  • Georgia
    • Atlanta, Georgia, United States, 30315
      • Treken Primary Care /ID# 234645
    • Atlanta, Georgia, United States, 30342-1605
      • Children's Healthcare of Atlanta - Ferry Rd /ID# 237005
    • Atlanta, Georgia, United States, 30342
      • Children's Ctr Digestive, US /ID# 237574
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance /ID# 237963
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute /ID# 234702
    • Stockbridge, Georgia, United States, 30281
      • Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 236342
  • Kansas
    • Wichita, Kansas, United States, 67214
      • KU Wichita Center for Clinical Research /ID# 234500
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Michael W. Simon, MD, PSC /ID# 236516
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Virgo Carter Pediatrics /ID# 234518
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413-2195
      • MNGI Digestive Health, P. A. /ID# 234437
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • GI associates and Endoscopy Ce /ID# 237969
    • Port Gibson, Mississippi, United States, 39150-2024
      • David M. Headley, MD, P.A. /ID# 238216
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Private Practice - Dr. Craig Spiegel /ID# 234545
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 234566
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102-4517
      • University of New Mexico /ID# 236983
  • New York
    • Bronx, New York, United States, 10468
      • Advantage Clinical Trials /ID# 237932
    • New York, New York, United States, 10032
      • Columbia University Medical Center and Morgan Stanley Children's Hospital of NY /ID# 235686
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University Brody School of Medicine /ID# 237509
    • Statesville, North Carolina, United States, 28625
      • PMG Research of Piedmont Healthcare-Statesville /ID# 238257
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Univ Oklahoma HSC /ID# 237546
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company /ID# 237669
  • Pennsylvania
    • Scottdale, Pennsylvania, United States, 15683
      • Frontier Clinical Research, LLC - Scottdale /ID# 238022
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research /ID# 237923
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital /ID# 237861
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research - West Ashley B /ID# 234678
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatric Research - Summerville /ID# 234674
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic, PA /ID# 236772
    • Jefferson City, Tennessee, United States, 37760
      • Accellacare of Knoxville /ID# 234462
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Med. Center /ID# 237536
    • Harlingen, Texas, United States, 78550
      • Valley Institute of Research /ID# 234475
    • Houston, Texas, United States, 77017-2337
      • Vilo Research Group Inc /ID# 238228
    • Houston, Texas, United States, 77051
      • Cullen Research /ID# 234482
    • Houston, Texas, United States, 77099-4307
      • Pioneer Research Solutions - Houston /ID# 236935
    • Plano, Texas, United States, 75093
      • AIM Trials /ID# 236364
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute /ID# 236932
    • Waxahachie, Texas, United States, 75165-1430
      • ClinPoint Trials /ID# 236615
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research /ID# 234515
  • Virginia
    • Franklin, Virginia, United States, 23851
      • Office of Maria Ona /ID# 234539
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc. (HRHR) /ID# 237252
    • Richmond, Virginia, United States, 23220-4459
      • Clinical Research Partners, LLC /ID# 237158
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multicare Institute for Research and Innovation /ID# 236979

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant weighs ≥ 18 kg at the time the parent/guardian/LAR and/or caregiver has provided signed consent.
• Female participants who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception.
• Participants must have completed study intervention in their lead-in study.

Inclusion Criteria for Phase 2 LIN-MD-62 or Phase 2 LIN-MD-63 and Phase 3 LIN-MD-64 completers who enroll in LIN-MD-66 after >28 days from last study intervention:

• Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit (Visit 1) and negative urine pregnancy test prior to the first dose on the Day 1 Visit (Visit 2).

• LIN-MD-63 completers only: Participants meet Rome III criteria for child/adolescent IBS: At least once per week for at least 2 months before the LIN-MD-66 Screening Visit (Visit 1), 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:

  • a) Improvement with defecation
  • b) Onset associated with a change in frequency of stool
  • c) Onset associated with a change in form (appearance) of stool

• Participants meet modified Rome III criteria for child/adolescent FC: For at least 2 months before the LIN-MD-66 Screening Visit (Visit 1), the participant has had 2 or fewer defecations (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) in the toilet per week. In addition, at least once per week, participant meets 1 or more of the following:

  • a) History of retentive posturing or excessive volitional stool retention
  • b) History of painful or hard BMs
  • c) Presence of a large fecal mass in the rectum
  • d) History of large diameter stools that may obstruct the toilet
  • e) At least 1 episode of fecal incontinence per week

Exclusion Criteria:

• Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class.
• Participant received an investigational drug, other than linaclotide, during the 30 days before the Screening Visit (Visit 1) or is planning to receive an investigational drug (other than that administered during this study) or use an investigational device at any time during the study.
• Female participants who are currently pregnant or nursing, or plan to become pregnant or nurse during the clinical study.
• Participant has required manual disimpaction any time prior to study intervention or disimpaction during in-patient hospitalization within 1 year prior to study intervention.

• Participant has any of the following conditions:

  • a) Down's syndrome or any other chromosomal disorder
  • b) Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displaced anus)
  • c) Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceral myopathies, visceral neuropathies)
  • d) Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
  • e) 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 by the participant.
• Participant has a mechanical bowel obstruction or pseudo-obstruction.
• 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 an active anal fissure (Note: history of anal fissure is not an exclusion).

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

  • a) Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit (Visit 1).
  • b) Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit (Visit 1)
  • c) An appendectomy or cholecystectomy during the 60 days before the Screening Visit
  • d) Other major surgery during the 30 days before the Screening Visit (Visit 1)
• Participant is receiving enteral tube feeding
• Participants who have positive urine drug screen results for cocaine, barbiturates, opiates, or cannabinoids will be excluded from study participation.

Exclusion Criteria for LIN-MD-62, LIN-MD-63 and LIN-MD-64 Completers Who Enroll in LIN-MD-66 > 28 Days From Last Study Intervention:

• Participant has a history of nonretentive fecal incontinence
• For LIN-MD-62 and LIN-MD-64 completers only:

Participant meets Rome III criteria for child/adolescent IBS: at least once per week for at least 2 months before Screening (Visit 1), 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:

• a) Improvement with defecation
• b) Onset associated with a change in the frequency of stool

• c) Onset associated with a change in form (appearance) of stool

  • Participant has a history of drug or alcohol abuse
  • Participant has any of the following conditions:
• a) Celiac disease, or positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy
• b) Cystic fibrosis
• c) 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 1)
• d) Lead toxicity, hypercalcemia
• e) Inflammatory bowel disease
• f) Childhood functional abdominal pain syndrome
• g) Childhood functional abdominal pain
• h) Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study
• i) Lactose intolerance that is associated with abdominal pain or discomfort and could confound the assessments in this study
• j) 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.)

• k) History of diabetic neuropathy

  • Participants who have positive urine drug screen results for cocaine, barbiturates, opiates, or cannabinoids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 72 μg linaclotide; An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.	Drug: Irritable Bowel Syndrome with Constipation (IBS-C) participants (LIN-MD-63 completers); Participants whom are between the ages of 7-11 years old at their time of enrollment will be assigned a dose (72 μg or 145 μg) based on their weight. Randomized doses (145 μg or 290 μg) will be assigned to participants whom are 12-17 years old at the time of enrollment.; Drug: Functional Constipation (FC) participants (LIN-MD-62 and LIN-MD-64 completers); Participants whom are between the ages of 6-11 years old at their time of enrollment will be assigned a dose of 72 μg. Randomized doses (72 μg or 145 μg) will be assigned to participants whom are 12-17 years old at the time of enrollment.
Active Comparator: 145 μg linaclotide; An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.	Drug: Irritable Bowel Syndrome with Constipation (IBS-C) participants (LIN-MD-63 completers); Participants whom are between the ages of 7-11 years old at their time of enrollment will be assigned a dose (72 μg or 145 μg) based on their weight. Randomized doses (145 μg or 290 μg) will be assigned to participants whom are 12-17 years old at the time of enrollment.; Drug: Functional Constipation (FC) participants (LIN-MD-62 and LIN-MD-64 completers); Participants whom are between the ages of 6-11 years old at their time of enrollment will be assigned a dose of 72 μg. Randomized doses (72 μg or 145 μg) will be assigned to participants whom are 12-17 years old at the time of enrollment.
Active Comparator: 290 μg linaclotide; An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.	Drug: Irritable Bowel Syndrome with Constipation (IBS-C) participants (LIN-MD-63 completers); Participants whom are between the ages of 7-11 years old at their time of enrollment will be assigned a dose (72 μg or 145 μg) based on their weight. Randomized doses (145 μg or 290 μg) will be assigned to participants whom are 12-17 years old at the time of enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	Number of Participants With Treatment-Emergent Adverse Events (TEAEs).	24 to 52 weeks

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Additional information on study locations near you may be found at AllerganClinicalTrials.com.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2019
• Primary Completion (Estimated): October 9, 2025
• Study Completion (Estimated): October 9, 2025

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation
• Other Study ID Numbers: LIN-MD-66; 2019-001955-38 (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.: No