Clinical trial NCT04166058: Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Constipation
Functional Constipation
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2019-11-18
Enrollment: 389
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: 24 to 52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates /ID# 237953
state: Alabama
city: Foley
country: United States
facility: G & L Research, LLC /ID# 238093
state: Alabama
city: Saraland
country: United States
facility: The Center for Clinical Trials Inc. /ID# 234605
state: Alabama
city: Hot Springs
country: United States
facility: HealthStar Research of Hot Springs PLLC /ID# 234608
state: Arkansas
city: Little Rock
country: United States
facility: Preferred Research Partners /ID# 237109
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas /ID# 238069
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center /ID# 237960
state: California
city: Corona
country: United States
facility: Kindred Medical Institute, LLC /ID# 237367
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials LLC /ID# 234629
state: California
city: San Diego
country: United States
facility: Medical Ctr for Clin Research /ID# 236911
state: California
city: Aurora
country: United States
facility: Lynn Institute of Denver /ID# 238086
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center /ID# 234417
state: District of Columbia
city: Doral
country: United States
facility: Prohealth Research Center /ID# 234659
state: Florida
city: Doral
country: United States
facility: Dolphin Medical Research /ID# 234676
state: Florida
city: Hialeah
country: United States
facility: Amedica Research Institute Inc /ID# 234666
state: Florida
city: Jacksonville
country: United States
facility: Nemours Childrens Specialty Care /ID# 237991
state: Florida
city: Miami
country: United States
facility: Elite Clinical Research /ID# 234651
state: Florida
city: Miami
country: United States
facility: My Preferred Research LLC /ID# 237943
state: Florida
city: Miami
country: United States
facility: South Miami Medical & Research Group Inc. /ID# 234654
state: Florida
city: Miami
country: United States
facility: Valencia Medical & Research Center /ID# 234671
state: Florida
city: Naples
country: United States
facility: Advanced Research for Health Improvement /ID# 238253
state: Florida
city: Orlando
country: United States
facility: Pediatric & Adult Research Center /ID# 234681
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital /ID# 234429
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research /ID# 234692
state: Florida
city: Atlanta
country: United States
facility: Treken Primary Care /ID# 234645
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Ferry Rd /ID# 237005
state: Georgia
city: Atlanta
country: United States
facility: Children's Ctr Digestive, US /ID# 237574
state: Georgia
city: Blue Ridge
country: United States
facility: River Birch Research Alliance /ID# 237963
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Institute /ID# 234702
state: Georgia
city: Stockbridge
country: United States
facility: Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 236342
state: Georgia
city: Wichita
country: United States
facility: KU Wichita Center for Clinical Research /ID# 234500
state: Kansas
city: Lexington
country: United States
facility: Michael W. Simon, MD, PSC /ID# 236516
state: Kentucky
city: Silver Spring
country: United States
facility: Virgo Carter Pediatrics /ID# 234518
state: Maryland
city: Minneapolis
country: United States
facility: MNGI Digestive Health, P. A. /ID# 234437
state: Minnesota
city: Flowood
country: United States
facility: GI associates and Endoscopy Ce /ID# 237969
state: Mississippi
city: Port Gibson
country: United States
facility: David M. Headley, MD, P.A. /ID# 238216
state: Mississippi
city: Bridgeton
country: United States
facility: Private Practice - Dr. Craig Spiegel /ID# 234545
state: Missouri
city: East Orange
country: United States
facility: Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 234566
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico /ID# 236983
state: New Mexico
city: Bronx
country: United States
facility: Advantage Clinical Trials /ID# 237932
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center /ID# 235686
state: New York
city: Greenville
country: United States
facility: East Carolina University - Brody School of Medicine /ID# 237509
state: North Carolina
city: Statesville
country: United States
facility: PMG Research of Piedmont Healthcare-Statesville /ID# 238257
state: North Carolina
city: Oklahoma City
country: United States
facility: Univ Oklahoma HSC /ID# 237546
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research Company /ID# 237669
state: Oklahoma
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC - Scottdale /ID# 238022
state: Pennsylvania
city: Smithfield
country: United States
facility: Duplicate_Frontier Clinical Research /ID# 237923
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital /ID# 237861
state: Rhode Island
city: Charleston
country: United States
facility: Coastal Pediatric Research - West Ashley B /ID# 234678
state: South Carolina
city: Summerville
country: United States
facility: Coastal Pediatric Research - Summerville /ID# 234674
state: South Carolina
city: Jackson
country: United States
facility: The Jackson Clinic, PA /ID# 236772
state: Tennessee
city: Jefferson City
country: United States
facility: Accellacare of Knoxville /ID# 234462
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Med. Center /ID# 237536
state: Texas
city: Harlingen
country: United States
facility: Valley Institute of Research /ID# 234475
state: Texas
city: Houston
country: United States
facility: Vilo Research Group Inc /ID# 238228
state: Texas
city: Houston
country: United States
facility: Cullen Research /ID# 234482
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions - Houston /ID# 236935
state: Texas
city: Plano
country: United States
facility: AIM Trials /ID# 236364
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute /ID# 236932
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials /ID# 236615
state: Texas
city: Saint George
country: United States
facility: Duplicate_Chrysalis Clinical Research /ID# 234515
state: Utah
city: Franklin
country: United States
facility: Office of Maria Ona /ID# 234539
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. (HRHR) /ID# 237252
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC /ID# 237158
state: Virginia
city: Tacoma
country: United States
facility: Duplicate_Multicare Institute for Research and Innovation /ID# 236979
state: Washington
city: London
country: Canada
facility: London Health Sciences Center- University Hospital /ID# 234309
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc /ID# 234618
state: Ontario
city: Stouffville
country: Canada
facility: Stouffville Medical Centre /ID# 234619
state: Ontario
city: Tiberias
country: Israel
facility: The Baruch Padeh Medical Center Poriya /ID# 234768
state: HaTsafon
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 236760
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital - Ein Kerem /ID# 234735
state: Yerushalayim
city: Amsterdam
country: Netherlands
facility: Duplicate_Academisch Medisch Centrum /ID# 237116
state: Noord-Holland
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: