Linaclotide Safety and Efficacy in 2 to 5-Year-Old Participants With Functional Constipation

NCT ID: NCT04110145

Last Updated: 2022-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2021-04-20

Brief Summary

The purpose of this study is to evaluate the dose response, safety, and efficacy of linaclotide when compared with placebo in pediatric participants, 2 to 5 years of age, with Functional Constipation.

Conditions

Functional Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cohort 1 (Linaclotide 18 μg)

Linaclotide 18 microgram (μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period.

Group Type: EXPERIMENTAL

Linaclotide

Intervention Type: DRUG

Linaclotide, capsules, mixed with water and administered orally, once daily in fasted state.

Cohort 2 (Linaclotide 36 μg)

Linaclotide 36 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period.

Group Type: EXPERIMENTAL

Linaclotide

Intervention Type: DRUG

Linaclotide, capsules, mixed with water and administered orally, once daily in fasted state.

Cohort 3 (Linaclotide 72 μg)

Linaclotide 72 μg, capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period.

Group Type: EXPERIMENTAL

Linaclotide

Intervention Type: DRUG

Linaclotide, capsules, mixed with water and administered orally, once daily in fasted state.

Final Cohort (Linaclotide 72 μg)

Linaclotide at the highest dose tested/determined to be safe (72 μg), capsules, mixed with water and administered orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period.

Group Type: EXPERIMENTAL

Linaclotide

Intervention Type: DRUG

Linaclotide, capsules, mixed with water and administered orally, once daily in fasted state.

Placebo Pooled

Matching placebo, orally, once daily in fasted state (30 minutes before any meal) for the 4-week Study Intervention Period pooled from Cohorts 1, 2, 3, and Final Cohort.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo, capsules, mixed with water and administered orally, once daily in fasted state

Interventions

Linaclotide

Linaclotide, capsules, mixed with water and administered orally, once daily in fasted state.

Intervention Type: DRUG

Placebo

Matching placebo, capsules, mixed with water and administered orally, once daily in fasted state

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant weighs ≥10 kilograms (kg) at the time the parent/guardian/legally authorized representative (LAR) has provided signed consent
• Participant meets modified Rome III criteria for FC: For at least 2 months before Screening (Visit 1) (for participants aged ≥ 4 years old), or for at least 1 month before Screening (Visit 1) (for participants aged < 4 years old), 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) per week.

In addition, at least once per week, participant must meet 1 or more of the following:

1. History of retentive posturing or excessive volitional stool retention

2. History of painful or hard bowel movements (BMs)

3. Presence of a large fecal mass in the rectum

4. History of large diameter stools that may obstruct the toilet

5. At least one episode of fecal incontinence per week after the acquisition of toileting skills

• Participant is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol-permitted rescue medicine
• Parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures
• Caregiver who will be completing the eDiary is able to read and/or understand the assessments in the eDiary device and must undergo training

Exclusion Criteria

• For participants aged ≥ 4 years old: 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:

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 has required manual dis-impaction any time prior to randomization or dis-impaction during in-patient hospitalization within 1 year 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 had surgery that meets any of the following criteria:

1. Surgery to remove a segment of the GI tract at any time before Screening (Visit 1)

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 Screening (Visit 1)

4. Other major surgery during the 30 days before Screening (Visit 1)

• Participant has a mechanical bowel obstruction or pseudo-obstruction.
• Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class
• Participant has any of the following conditions:

1. Celiac disease, or positive serological test for celiac disease or the condition is suspected but 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 Screening (Visit 1)

4. Down's syndrome or any other chromosomal disorder

5. Active anal fissure (ie, participant reports having streaks of blood on the stool or on toilet paper and/or pain/crying with bowel movement within 2 weeks prior to Screening). (Note: Anal fissures that have resolved at least 2 weeks prior to screening would not be exclusionary.) However, if in the investigator's opinion, an anal fissure(s) may be the primary cause of participant's modified Rome III FC criteria, the participant would not be eligible to participate in the study.

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 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 symptoms which 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 before the Randomization Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment.)

• Participant received a study intervention during the 30 days before Screening (Visit 1) or is planning to receive study intervention (other than that administered during this 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
• For participants aged ≥ 4 years old: Participant has a history of non-retentive fecal incontinence

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ironwood Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Allergan

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Muslin

Role: STUDY_DIRECTOR

Allergan

Locations

Central Research Associates, Inc

Birmingham, Alabama, United States

HealthStar Research

Hot Springs, Arkansas, United States

Preferred Clinical Research Partners

Little Rock, Arkansas, United States

Advanced Research Center

Anaheim, California, United States

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, United States

Center for Clinical Trials, LLC

Paramount, California, United States

Prohealth Research Center

Doral, Florida, United States

South Miami Medical & Research Group, Inc.

Miami, Florida, United States

River Birch Research Alliance, LLC

Blue Ridge, Georgia, United States

SleepCare Research Institute, Inc.

Stockbridge, Georgia, United States

Virgo Carter Pediatrics

Silver Spring, Maryland, United States

Minnesota Gastroenterology PA

Minneapolis, Minnesota, United States

David M. Headley, MD, P.A.

Port Gibson, Mississippi, United States

Foundation Pediatrics Med Clinical Research Partners, LLC

East Orange, New Jersey, United States

Advantage Clinical Trials

The Bronx, New York, United States

Coastal Pediatric Research

Charleston, South Carolina, United States

Coastal Pediatric Research

Mt. Pleasant, South Carolina, United States

Clinical Research Partners, LLC

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002126-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LIN-MD-67

Identifier Type: -

Identifier Source: org_study_id