Linaclotide for Pediatric Constipation

No longer recruiting at 61 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Celiac, Cystic fibrosis, Hypothyroidism, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores linaclotide as a treatment for young children aged 2 to 5 with functional constipation (FC), a condition characterized by infrequent or difficult bowel movements. The trial aims to determine if linaclotide can safely and effectively reduce constipation symptoms compared to a placebo (a pill with no active medicine). Initially, participants have a 50% chance of receiving either linaclotide or a placebo for 12 weeks, after which all will receive linaclotide for an additional 24 weeks. Children who have had 2 or fewer bowel movements a week for at least a month may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants an opportunity to contribute to the development of a new treatment for constipation.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using laxatives, suppositories, or enemas, you should not use them within 24 hours before a bowel movement for at least one month before screening. Please consult with the trial team for more details.

Will I have to stop taking my current medications?

The trial information does not specify if participants must stop taking their current medications. However, certain conditions and treatments, like untreated hypothyroidism or unstable thyroid hormone doses, are exclusion criteria, which might imply some medication adjustments could be necessary.

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

Research shows that linaclotide is usually well-tolerated for treating constipation in children. In past studies with kids aged 6 to 17, diarrhea emerged as the most common side effect. While some children might experience stomach issues, linaclotide is generally as safe as other treatments. The FDA has approved linaclotide for older children, which reassures its safety. However, since this study focuses on younger children, ages 2 to 5, the results will clarify its safety for this age group. ^{1 2 3 4 5}

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

Linaclotide is unique because it targets the underlying causes of constipation by increasing fluid secretion in the intestines, which can help ease bowel movements. Unlike some standard treatments that primarily focus on softening stool or stimulating bowel contractions, linaclotide offers a different approach by enhancing the natural secretion of fluids in your gut. Researchers are excited about its potential to provide a more effective and long-lasting solution for pediatric constipation, especially for children who haven't found relief with existing treatments.

What evidence suggests that this trial's treatments could be effective for pediatric constipation?

Research has shown that linaclotide helps treat constipation in children. Studies found it increases the number of bowel movements more than a placebo. In this trial, some participants will receive linaclotide for 12 weeks, while others will receive a placebo for the same duration. Trials with older children showed that linaclotide doubled the number of bowel movements over 12 weeks. It is well-tolerated, causing few side effects. Linaclotide is already approved for treating constipation in adults and older children, supporting its potential use in younger children. These findings suggest linaclotide could be a promising option for managing constipation in kids aged 2 to 5. ^{1 3 6 7 8}

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 2 to 5 with functional constipation, meeting specific criteria like having fewer than two bowel movements per week without laxatives. They must not have certain conditions like cystic fibrosis or untreated hypothyroidism, and their caregiver must be able to use an eDiary.

Inclusion Criteria

Participant meets modified Rome IV criteria for FC: For at least 1 month before Screening (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) per week. In addition, at least once per week, participant must meet 1 or more of the following:

You have a history of holding in your bowel movements or intentionally not going to the bathroom when you need to.

I have a significant blockage in my rectum.

Exclusion Criteria

You have a mental health condition that is not well managed or controlled and could affect your ability to take part in the study.

I have a birth defect affecting my anus.

I have had symptoms of an active anal fissure within the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily doses of oral Linaclotide capsules or matching placebo for 12 weeks

12 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants who completed study intervention in Part 1 will receive linaclotide for 24 weeks

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Linaclotide
• Placebo for Linaclotide

Trial Overview The study tests Linaclotide against a placebo in young children with functional constipation. It's split into two parts: the first part randomly assigns participants to either the drug or placebo for 12 weeks; the second part gives all participants Linaclotide for another 24 weeks.

How Is the Trial Designed?

Group I: Part 2 Linaclotide Experimental Treatment 1 Intervention

Participants who completed study intervention in Part 1 of this study or the Phase 2 Study LIN-MD-67 will receive 24 weeks of linaclotide exposure.

Group II: Part 1 Placebo Experimental Treatment 1 Intervention

Participants will receive placebo for 12 weeks.

Group III: Part 1 Linaclotide Experimental Treatment 1 Intervention

Participants will receive linaclotide for 12 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 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 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 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 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]

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 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 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]

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. 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 ...

4. 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125323003989

Efficacy and safety of linaclotide in treating functional ... This study investigated the efficacy and safety of linaclotide in children and adolescents with functional constipation or IBS with predominant constipation, ...

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- ...

8. investor.ironwoodpharma.com investor.ironwoodpharma.com/press-releases/press-release-details/2023/Ironwood-Presents-New-Data-on-Potential-of-Linaclotide-for-Functional-Constipation-in-Children-and-Adolescents-Ages-6-17-Years-Old-at-Digestive-Disease-Week-2023/default.aspx

Ironwood Presents New Data on Potential of Linaclotide for ... Linaclotide was generally well-tolerated and exhibited a safety profile consistent with a prior pediatric Phase II study in functional ...