Long-Term Safety of Linaclotide for Constipation

No longer recruiting at 146 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of linaclotide, a medication for constipation. It includes children and teens with functional constipation or irritable bowel syndrome with constipation (IBS-C) who participated in earlier linaclotide studies. Participants will take different doses of linaclotide over 24 or 52 weeks to assess tolerance. Suitable candidates experience frequent constipation issues, such as fewer than three bowel movements a week or painful, hard stools. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

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

Research has shown that linaclotide is generally safe. One study followed individuals with chronic constipation or irritable bowel syndrome for up to two years and confirmed its long-term safety. In two other 12-week studies, linaclotide reduced symptoms without major safety concerns. Another study focused on individuals unresponsive to other treatments and found linaclotide both effective and safe. These findings suggest that many patients tolerate linaclotide well. While some side effects can occur, research indicates that linaclotide is safe for many users. ^{1 2 3 4 5}

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

Researchers are excited about linaclotide for constipation because it offers a unique way to tackle the problem. Unlike other treatments that typically work by softening stool or stimulating bowel movements, linaclotide works by increasing fluid secretion in the intestines and accelerating food transit through the gut. This mechanism can provide relief more naturally and could potentially lead to improved comfort and bowel regularity for patients. Additionally, linaclotide is convenient as it's taken orally and can be swallowed whole or sprinkled on food, making it easy to incorporate into daily routines.

What is the effectiveness track record for linaclotide in treating constipation?

Studies have shown that linaclotide effectively treats chronic constipation and irritable bowel syndrome with constipation (IBS-C). Research indicates that linaclotide significantly reduces symptoms such as infrequent bowel movements and abdominal discomfort. In adults with these conditions, linaclotide provided quick and lasting relief. It is generally well-tolerated, meaning most people can use it without major side effects. These findings suggest linaclotide could be a helpful option for managing constipation-related issues. ^{3 4 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 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

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3638410/

Linaclotide (Linzess) for Irritable Bowel syndrome With ... CONCLUSION. Linaclotide is an efficacious, well-tolerated treatment option for adults with irritable bowel syndrome with constipation (IBS–C) and chronic ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1010863

Two Randomized Trials of Linaclotide for Chronic ... In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00765999

An Open-Label, Long-Term Safety Study of Linaclotide in ... The objective of this study is to assess the long-term safety of linaclotide administered to patients with chronic constipation (CC) or irritable bowel ...

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

Efficacy in Functional Constipation | LINZESS® (linaclotide) LINZESS demonstrated 2x greater improvement in bowel movement frequency over 12 weeks · LINZESS provided early and lasting improvement of bowel movement ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/nmo.14938

Efficacy and safety of linaclotide in treatment‐resistant ... This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30791771/

Safety and tolerability of linaclotide for the treatment ... These pooled analyses of patients treated for ≤104 weeks confirm linaclotide's overall safety.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00765999

An Open-Label, Long-Term Safety Study of Linaclotide in ... The objective of this study is to assess the long-term safety of linaclotide administered to patients with chronic constipation (CC) or irritable bowel ...

8. ema.europa.eu ema.europa.eu/en/documents/variation-report/constella-h-c-2490-p46-019-epar-assessment-report_en.pdf

Constella, INN-linaclotide - European Medicines Agency The study with the title “A Long-term Safety Study of Oral Linaclotide Administered to Paediatric. Participants with Functional Constipation (FC) or Irritable ...