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

Functional Constipation Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04166058
• Other study ID #: LIN-MD-66
• Secondary ID: 2019-001955-38
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 19, 2019
• Est. completion date: June 5, 2025

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 389
• Est. completion date: June 5, 2025
• Est. primary completion date: June 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Constipation
• Functional Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Constipation
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	London Health Sciences Center- University Hospital /ID# 234309	London	Ontario
Canada	Bluewater Clinical Research Group Inc /ID# 234618	Sarnia	Ontario
Canada	Stouffville Medical Centre /ID# 234619	Stouffville	Ontario
Israel	Hadassah Hebrew University Hospital - Ein Kerem /ID# 234735	Jerusalem	Yerushalayim
Israel	The Chaim Sheba Medical Center /ID# 236760	Ramat Gan	Tel-Aviv
Israel	The Baruch Padeh Medical Center Poriya /ID# 234768	Tiberias	HaTsafon
Netherlands	Duplicate_Academisch Medisch Centrum /ID# 237116	Amsterdam	Noord-Holland
United States	University of New Mexico /ID# 236983	Albuquerque	New Mexico
United States	Advanced Research Center /ID# 237960	Anaheim	California
United States	Children's Ctr Digestive, US /ID# 237574	Atlanta	Georgia
United States	Children's Healthcare of Atlanta - Ferry Rd /ID# 237005	Atlanta	Georgia
United States	Treken Primary Care /ID# 234645	Atlanta	Georgia
United States	Lynn Institute of Denver /ID# 238086	Aurora	Colorado
United States	Central Research Associates /ID# 237953	Birmingham	Alabama
United States	River Birch Research Alliance /ID# 237963	Blue Ridge	Georgia
United States	Private Practice - Dr. Craig Spiegel /ID# 234545	Bridgeton	Missouri
United States	Advantage Clinical Trials /ID# 237932	Bronx	New York
United States	Coastal Pediatric Research - West Ashley B /ID# 234678	Charleston	South Carolina
United States	Kindred Medical Institute, LLC /ID# 237367	Corona	California
United States	Dolphin Medical Research /ID# 234676	Doral	Florida
United States	Prohealth Research Center /ID# 234659	Doral	Florida
United States	Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 234566	East Orange	New Jersey
United States	GI associates and Endoscopy Ce /ID# 237969	Flowood	Mississippi
United States	G & L Research, LLC /ID# 238093	Foley	Alabama
United States	Cook Children's Med. Center /ID# 237536	Fort Worth	Texas
United States	Office of Maria Ona /ID# 234539	Franklin	Virginia
United States	East Carolina University - Brody School of Medicine /ID# 237509	Greenville	North Carolina
United States	Valley Institute of Research /ID# 234475	Harlingen	Texas
United States	Amedica Research Institute Inc /ID# 234666	Hialeah	Florida
United States	HealthStar Research of Hot Springs PLLC /ID# 234608	Hot Springs	Arkansas
United States	Cullen Research /ID# 234482	Houston	Texas
United States	Pioneer Research Solutions - Houston /ID# 236935	Houston	Texas
United States	Vilo Research Group Inc /ID# 238228	Houston	Texas
United States	The Jackson Clinic, PA /ID# 236772	Jackson	Tennessee
United States	Nemours Childrens Specialty Care /ID# 237991	Jacksonville	Florida
United States	Accellacare of Knoxville /ID# 234462	Jefferson City	Tennessee
United States	Michael W. Simon, MD, PSC /ID# 236516	Lexington	Kentucky
United States	Applied Research Center of Arkansas /ID# 238069	Little Rock	Arkansas
United States	Preferred Research Partners /ID# 237109	Little Rock	Arkansas
United States	Elite Clinical Research /ID# 234651	Miami	Florida
United States	My Preferred Research LLC /ID# 237943	Miami	Florida
United States	South Miami Medical & Research Group Inc. /ID# 234654	Miami	Florida
United States	Valencia Medical & Research Center /ID# 234671	Miami	Florida
United States	MNGI Digestive Health, P. A. /ID# 234437	Minneapolis	Minnesota
United States	Advanced Research for Health Improvement /ID# 238253	Naples	Florida
United States	Columbia University Irving Medical Center /ID# 235686	New York	New York
United States	Health Research of Hampton Roads, Inc. (HRHR) /ID# 237252	Newport News	Virginia
United States	IPS Research Company /ID# 237669	Oklahoma City	Oklahoma
United States	Univ Oklahoma HSC /ID# 237546	Oklahoma City	Oklahoma
United States	Nemours Children's Hospital /ID# 234429	Orlando	Florida
United States	Pediatric & Adult Research Center /ID# 234681	Orlando	Florida
United States	Oviedo Medical Research /ID# 234692	Oviedo	Florida
United States	Center for Clinical Trials LLC /ID# 234629	Paramount	California
United States	AIM Trials /ID# 236364	Plano	Texas
United States	David M. Headley, MD, P.A. /ID# 238216	Port Gibson	Mississippi
United States	Rhode Island Hospital /ID# 237861	Providence	Rhode Island
United States	Clinical Research Partners, LLC /ID# 237158	Richmond	Virginia
United States	Chrysalis Clinical Research /ID# 234515	Saint George	Utah
United States	Sun Research Institute /ID# 236932	San Antonio	Texas
United States	Medical Ctr for Clin Research /ID# 236911	San Diego	California
United States	The Center for Clinical Trials Inc. /ID# 234605	Saraland	Alabama
United States	Frontier Clinical Research, LLC - Scottdale /ID# 238022	Scottdale	Pennsylvania
United States	Virgo Carter Pediatrics /ID# 234518	Silver Spring	Maryland
United States	Frontier Clinical Research /ID# 237923	Smithfield	Pennsylvania
United States	PMG Research of Piedmont Healthcare-Statesville /ID# 238257	Statesville	North Carolina
United States	Clinical Research Institute /ID# 234702	Stockbridge	Georgia
United States	Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 236342	Stockbridge	Georgia
United States	Coastal Pediatric Research - Summerville /ID# 234674	Summerville	South Carolina
United States	Duplicate_Multicare Institute for Research and Innovation /ID# 236979	Tacoma	Washington
United States	Children's National Medical Center /ID# 234417	Washington	District of Columbia
United States	ClinPoint Trials /ID# 236615	Waxahachie	Texas
United States	KU Wichita Center for Clinical Research /ID# 234500	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events	Number of Participants With Treatment-Emergent Adverse Events (TEAEs).	24 to 52 weeks