Linaclotide for Pediatric Constipation

Recruiting at 55 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

123 Participants Needed

Trial Summary

What is the purpose of this trial?

Functional constipation (FC) is a common healthcare problem in children of all ages, potentially due to genetic predisposition, inadequate fiber and fluid intake, and immobility. Currently, there are no pharmacological therapies approved for the treatment of FC. This study will assess adverse events and change in disease activity with linaclotide therapy in participants with FC. Linaclotide is an approved drug being developed for the treatment of FC in pediatric patients, ages 2 to 5, who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. All participants in Part 2 will receive linaclotide. Approximately 116 participants aged 2 to 5 years with FC will be enrolled in this study at around 45 sites worldwide. Participants will receive daily doses of oral Linaclotide capsules or matching placebo for 12 weeks in Part 1 of the study. In Part 2, the open label long-term safety extension, participants with FC who completed study intervention in Part 1 of Study M21-572 or the Phase 2 Study LIN-MD-67 will receive linaclotide for 24 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

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.

What data supports the idea that Linaclotide for Pediatric Constipation is an effective drug?

The available research shows that Linaclotide is effective in treating constipation in adults with irritable bowel syndrome and chronic idiopathic constipation. In studies, Linaclotide provided more relief from constipation symptoms compared to a placebo, with improvements in pain and bowel movements. However, it is important to note that there are no direct comparisons with other laxatives, and some patients experienced side effects like diarrhea. While these findings are promising for adults, there is no specific data provided for its effectiveness in children with constipation. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Linaclotide for pediatric constipation?

Linaclotide has been shown to be effective in adults for conditions like irritable bowel syndrome with constipation and chronic idiopathic constipation, where it helps increase stool frequency and improve bowel movements. While these studies are in adults, they suggest that Linaclotide may help with constipation by increasing intestinal fluid secretion and speeding up bowel movements. ^{1 2 3 4 5}

What safety data exists for Linaclotide in treating constipation?

Linaclotide has been evaluated in several studies primarily for adults with irritable bowel syndrome with constipation and chronic idiopathic constipation. It is generally well tolerated, with the most common adverse effect being diarrhea, which can be severe or prolonged in some cases. About 10% of patients discontinued due to gastrointestinal adverse effects. There is no safety data for use during pregnancy, and it should be avoided in such cases. Linaclotide has low oral bioavailability and acts locally in the gastrointestinal tract. It has been shown to improve bowel function and abdominal symptoms compared to placebo in clinical trials. ^{1 2 3 4 6}

Is linaclotide safe for use in humans?

Linaclotide is generally safe for use in humans, but it can cause diarrhea, which was the most common side effect in studies. Some people may experience severe or prolonged diarrhea, and about 10% of patients stopped using it due to gastrointestinal issues. ^{1 2 3 4 6}

Is the drug Linaclotide a promising treatment for pediatric constipation?

Linaclotide is a promising drug because it helps increase bowel movements and reduces abdominal pain, improving the quality of life for people with constipation. It has been shown to be effective in treating constipation-related symptoms and is generally well tolerated. ^{1 6 7 8 9}

How is the drug Linaclotide unique for treating pediatric constipation?

Linaclotide is unique because it is a guanylate cyclase-C receptor agonist that works by increasing fluid secretion in the intestines, which helps to improve bowel movements and relieve constipation. It is minimally absorbed, acting locally in the gut, and has shown effectiveness in treating constipation-related conditions in adults, suggesting potential benefits for pediatric use. ^{1 6 7 8 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. Japan 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]. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. [2018]