Linaclotide for Pediatric Constipation

No longer recruiting at 53 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must not be taking: Laxatives, Suppositories, Enemas

Disqualifiers: Celiac, Cystic fibrosis, Hypothyroidism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug linaclotide treats constipation in young children. Researchers are testing different doses to assess their impact on symptoms and any possible side effects. The goal is to find a safe and effective treatment for children who frequently have fewer than two bowel movements a week, often with hard or painful stool. Children experiencing these symptoms for at least a month might be suitable for the trial. Participants will need to visit the hospital or clinic regularly for checkups and assessments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants stop using any laxatives before the study begins, but it does not specify about other medications. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that linaclotide is generally safe for children. In studies with children aged 2-5, linaclotide proved safe, with diarrhea as a common side effect. Another study involving children aged 6-17 also reported diarrhea as the most frequent issue, but overall, linaclotide was considered safe.

These findings suggest that linaclotide is safe for children with constipation. Since the FDA has already approved linaclotide for other conditions, confidence in its safety exists. However, like any medication, monitoring for side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for constipation?

Unlike the standard treatments for pediatric constipation, which often rely on fiber supplements, laxatives, or stool softeners, Linaclotide works by targeting the guanylate cyclase-C receptor in the intestines. This unique mechanism increases fluid secretion and speeds up bowel movements, potentially offering a more direct and effective relief for constipation. Researchers are excited about Linaclotide because it represents a new class of treatment that could provide relief more efficiently and with fewer side effects compared to traditional options. Additionally, Linaclotide's oral administration as a capsule mixed with water is convenient and non-invasive, making it a promising option for children.

What evidence suggests that linaclotide might be an effective treatment for pediatric constipation?

Research shows that linaclotide helps treat constipation in children by increasing the number of weekly bowel movements, providing significant relief. Studies have found that it is well tolerated across different age groups, including young children aged 2-5, and remains effective even at lower doses. In older children aged 6-17, linaclotide doubled the frequency of bowel movements over several weeks. This evidence suggests that linaclotide is a promising option for managing constipation in children. Participants in this trial will receive different doses of linaclotide or a placebo to further evaluate its effectiveness and safety. ^{1 2 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for children aged 6 months to less than 2 years with functional constipation. They must meet certain criteria like having a history of hard bowel movements or infrequent defecation, and their parents must be able to use an eDiary for tracking. Children with conditions like celiac disease, cystic fibrosis, untreated hypothyroidism, chromosomal disorders, or any condition affecting drug absorption cannot participate.

Inclusion Criteria

The person filling out the eDiary for me can read, understand it, and will be trained.

I meet the criteria for functional constipation based on my symptoms.

You have bowel movements less than two times a week without using any medications to help you go to the bathroom in the past day.

Exclusion Criteria

I have celiac disease or it's suspected but not confirmed by a biopsy.

I have cystic fibrosis.

My thyroid condition is stable and has been treated consistently for the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral solution of linaclotide or placebo once daily for 4 weeks

4 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Linaclotide
• Placebo

Trial Overview The study tests Linaclotide against a placebo in treating pediatric functional constipation. Initially, different dosages are given consecutively in three groups; later participants are randomly assigned to either the drug or placebo. The treatment involves daily oral solution intake over four weeks at various global sites.

How Is the Trial Designed?

Group I: Part 2, Placebo Experimental Treatment 1 Intervention

Participants will receive placebo capsules mixed with water and administered orally in Part 2 for 4 weeks.

Group II: Part 2, Linaclotide Experimental Treatment 1 Intervention

Participants will receive Linaclotide capsules mixed with water and administered orally in Part 2 for 4 weeks.

Group III: Part 1, Linaclotide Dose C Experimental Treatment 1 Intervention

Linaclotide Dose C capsules, mixed with water and administered orally, once daily for 4 weeks

Group IV: Part 1, Linaclotide Dose B Experimental Treatment 1 Intervention

Linaclotide Dose B capsules, mixed with water and administered orally, once daily for 4 weeks

Group V: Part 1, Linaclotide Dose A Experimental Treatment 1 Intervention

Linaclotide Dose A capsules, mixed with water and administered orally, once daily for 4 weeks

Linaclotide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Approved in European Union as Constella for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)

Approved in Canada as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Ironwood Pharmaceuticals, Inc.

Industry Sponsor

Trials

42

Recruited

17,100+

Published Research Related to This Trial

Linaclotide (Linzess) is an effective treatment for patients suffering from irritable bowel syndrome with constipation and chronic idiopathic constipation, helping to relieve symptoms.

The medication works by increasing fluid secretion in the intestines and accelerating bowel movements, which can significantly improve the quality of life for those affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. Thomas, RH., Allmond, K.[2022]

Linaclotide is a promising new treatment for irritable bowel syndrome with constipation (IBS-C) and chronic constipation, showing effectiveness in clinical trials, particularly in two Phase III studies for each condition.

The drug is well-tolerated and offers a new option for patients who do not respond well to existing treatments, although its exact position among current therapies will be determined after FDA approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. Lee, N., Wald, A.[2017]

Linaclotide is a newly approved treatment for moderate to severe irritable bowel syndrome with constipation (IBS-C) that works by stimulating fluid secretion and increasing colonic transit in the gastrointestinal tract.

In phase III trials, linaclotide significantly improved abdominal pain and bowel function compared to placebo, with a good safety profile, although the most common side effect was diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. McCormack, PL.[2022]

Linaclotide has been shown to provide more frequent relief from constipation-related symptoms compared to a placebo in two clinical trials involving about 1600 patients, lasting 3 to 6 months.

However, it can cause significant gastrointestinal side effects, particularly diarrhea, which affected 20% of patients and led to discontinuation in about 10%, raising concerns about its safety and the lack of evidence showing it is more effective than other laxatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. [2017]

Linaclotide significantly improves bowel function in patients with irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC), with a relative risk of response to treatment of 1.95 for IBS-C and 4.26 for CC compared to placebo, based on a meta-analysis of 6 trials.

The treatment also effectively reduces abdominal pain, bloating, and overall symptom severity, demonstrating its efficacy as a therapeutic option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. Videlock, EJ., Cheng, V., Cremonini, F.[2018]

Linaclotide is effective for treating moderate to severe irritable bowel syndrome with constipation, showing significant improvements in symptoms compared to placebo, with a combined response rate of 12.6% to 22.8%.

The only notable adverse effect of linaclotide is diarrhea, making it a relatively safe option for patients who do not respond to other treatments for their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. Carballo, F.[2019]

In a study involving 36 women with constipation-predominant irritable bowel syndrome, linaclotide at a dose of 1000 micrograms significantly improved colonic transit and bowel function, leading to faster bowel movements and better stool consistency.

The treatment was found to be safe with no significant safety issues reported, indicating that linaclotide could be a promising option for managing symptoms in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Andresen, V., Camilleri, M., Busciglio, IA., et al.[2022]

Linaclotide (Linzess) is less expensive than lubiprostone (Amitiza) for treating chronic idiopathic constipation, with costs of $946 versus $1,015 based on patient satisfaction responses.

While linaclotide showed slightly lower effectiveness in terms of weekly spontaneous bowel movements (58.6% vs 59.6%), it was more effective in overall treatment satisfaction (39.3% vs 35.0%), making it a cost-effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States. Huang, H., Taylor, DC., Carson, RT., et al.[2017]

Linaclotide is an effective treatment for irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC), showing significant improvements in bowel movement frequency and overall symptom relief in clinical studies conducted in Japan.

The drug works by increasing intracellular cGMP through its action on the guanylate cyclase-C receptor, enhancing fluid secretion and gastrointestinal transit, while maintaining a favorable safety profile with manageable side effects like diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of linaclotide (Linzess&#174;), a novel therapeutic agent for irritable bowel syndrome with constipation and chronic constipation]. Keto, Y., Kosako, M.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38211604/

Efficacy and safety of linaclotide in treating functional ... Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food ...

2. gi.org gi.org/journals-publications/ebgi/abuheija_may2024/

Linaclotide Effective for Functional Constipation in 6-17 ... In this double-blinded, randomized, placebo-controlled trial linaclotide improved SBMs per week over baseline significantly.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38962910/

Safety and efficacy of linaclotide in children aged 2-5 years ... Conclusions: Linaclotide was well tolerated in this pediatric population and an efficacy trend was seen with linaclotide 72 μg versus placebo. Keywords: ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04026113

NCT04026113 | Linaclotide Safety and Efficacy in Pediatric ... Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre ...

5. linzesshcp.com linzesshcp.com/linzess-fc-efficacy

Efficacy in Functional Constipation | LINZESS® (linaclotide) Functional constipation (6-17 years of age) efficacy data · LINZESS demonstrated 2x greater improvement in bowel movement frequency over 12 weeks · LINZESS ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04026113

NCT04026113 | Linaclotide Safety and Efficacy in Pediatric ... 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 ...

7. linzesshcp.com linzesshcp.com/linzess-FC-safety

LINZESS® (linaclotide) Safety Profile Among FC Patients In pediatric patients 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg LINZESS-treated patients in the FC double-blind placebo- ...