Long-Term Safety of Linaclotide for Constipation

Recruiting at 143 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: Cocaine, Barbiturates, Opiates, Cannabinoids

Disqualifiers: Down's syndrome, Celiac disease, Inflammatory bowel disease, 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: 24 to 52 weeks

389 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests linaclotide, a medication that helps relieve constipation by increasing fluid in the intestines, in children aged 6-17 with constipation issues. Linaclotide is approved for treating certain types of constipation.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking another investigational drug or have a positive drug screen for certain substances.

Is linaclotide safe for long-term use in humans?

Linaclotide is generally considered safe for long-term use in humans, with the most common side effect being diarrhea. It has been studied for conditions like irritable bowel syndrome with constipation and chronic constipation, showing a good safety profile in clinical trials. ^{1 2 3 4 5}

What makes the drug Linaclotide unique for treating constipation?

Linaclotide is unique for treating constipation because it works by increasing the secretion of chloride and water in the intestines, which helps to soften stools and stimulate bowel movements. This mechanism of action is different from other common treatments like fiber supplements or laxatives, which primarily add bulk to stools or stimulate bowel contractions. ^{6 7 8 9 10}

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

The review on chronic idiopathic constipation mentions that linaclotide, a secretagogue (a substance that promotes secretion), can be effective for patients who do not respond to other treatments, suggesting its potential benefit for constipation. ^{11 12 13 14 15}

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 6-17 with Functional Constipation (FC) or Irritable Bowel Syndrome with Constipation (IBS-C) who completed prior studies LIN-MD-62, LIN-MD-63, or LIN-MD-64. They must have specific symptoms like large stools that may block the toilet and infrequent bowel movements without laxatives. Participants need to weigh at least 18 kg and girls of childbearing age must not be pregnant and agree to use contraception.

Inclusion Criteria

I am a woman who can have children and have had negative pregnancy tests.

I have had painful or hard bowel movements.

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:

Exclusion Criteria

I have had diabetic neuropathy.

I have not had surgery in my abdomen, pelvis, or behind the peritoneum in the last 6 months.

I have celiac disease or a positive test for it without a confirming biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linaclotide for 24 weeks (FC) or 52 weeks (IBS-C)

24 to 52 weeks

Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Linaclotide

Trial Overview The study tests the long-term safety of a medication called linaclotide in pediatric patients over a period of either 24 weeks for FC participants or 52 weeks for IBS-C participants. It's an open-label Phase 3 trial, meaning both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: 72 μg linaclotide Active Control 2 Interventions

An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.

Group II: 145 μg linaclotide Active Control 2 Interventions

An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.

Group III: 290 μg linaclotide Active Control 1 Intervention

An oral capsule that is taken once daily. It may be taken whole or sprinkled into 1 teaspoonful of applesauce or 30mL of bottled water.

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

Allergan

Lead Sponsor

Trials

782

Recruited

277,000+

Brent Saunders

Allergan

Chief Executive Officer since 2015

JD and MBA from Temple University

Dr. David Nicholson

Allergan

Chief Medical Officer since 2015

MD from Harvard Medical School

Ironwood Pharmaceuticals, Inc.

Industry Sponsor

Trials

42

Recruited

17,100+

Published Research Related to This Trial

Polyethylene glycol is the first-line treatment for chronic idiopathic constipation (CIC), while stimulant laxatives are recommended as a second-line option, highlighting the importance of effective pharmacological management.

Emerging treatments like prucalopride, linaclotide, and plecanatide offer additional options for patients who do not respond to standard therapies, although availability may vary by region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. Bassotti, G., Usai Satta, P., Bellini, M.[2021]

In a study of 30 patients with distal ulcerative colitis, those treated with 5-aminosalicylic acid (5-ASA) suppositories had a significantly higher remission rate of 92% after one year compared to only 21% in the placebo group.

The treatment was found to be safe, with no side effects reported, indicating that 5-ASA is an effective option for maintaining remission in patients with distal ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. D'Arienzo, A., Panarese, A., D'Armiento, FP., et al.[2013]

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 (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 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]

Linagliptin is an effective treatment for type 2 diabetes, leading to significant reductions in hemoglobin A1c and blood glucose levels, and can be taken at a standard dose of 5 mg daily without needing adjustments for patients with kidney or liver issues.

While linagliptin is generally well tolerated and does not cause weight gain, there is a higher risk of hypoglycemia when used with insulin secretagogues, highlighting the need for careful monitoring in such combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. Neumiller, JJ.[2015]

Citations

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

Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. [2021]

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

5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Oral 4-aminosalicylic acid versus 5-aminosalicylic acid slow release tablets. Double blind, controlled pilot study in the maintenance treatment of Crohn's ileocolitis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study. [2019]

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

Improving delivery of aminosalicylates in ulcerative colitis: effect on patient outcomes. [2021]

6. Spain pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. [2019]

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

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

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

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

10. England pubmed.ncbi.nlm.nih.gov

Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Linagliptin safety profile: A systematic review. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Safety of lansoprazole. [2019]

13. Austria pubmed.ncbi.nlm.nih.gov

[Side effects and safety of the new histamine H2 receptor antagonist ranitidine in the long-term treatment of patients with stomach and duodenal ulcers]. [2013]

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

Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. [2015]

15. England pubmed.ncbi.nlm.nih.gov

Safety profile of long-term H2-antagonist therapy. [2019]