Linaclotide for Pediatric Constipation
Recruiting in Palo Alto (17 mi)
+36 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AbbVie
Must not be taking: Laxatives, Suppositories, Enemas
Disqualifiers: Celiac, Cystic fibrosis, Hypothyroidism, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests linaclotide, a medication that may help young children with constipation by making their stools softer and easier to pass. The study involves children aged 6 months to less than 2 years who struggle with constipation.
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.
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 increases stool frequency and decreases stool consistency. Although these studies are in adults, they suggest that Linaclotide may help with constipation by increasing intestinal fluid secretion and speeding up bowel movements.
12345Is linaclotide safe for treating constipation in children?
Linaclotide has been studied in adults for conditions like irritable bowel syndrome with constipation, and the most common side effect is diarrhea, which can sometimes be severe. It is generally well tolerated, but about 10% of patients stopped using it due to gastrointestinal issues. There is no safety data for its use during pregnancy, and it should be used cautiously in people prone to fluid and electrolyte imbalances.
12346How 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 relieve constipation. Unlike some other treatments, it acts locally in the gut and has a low risk of systemic side effects due to its minimal absorption into the bloodstream.
16789Eligibility Criteria
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.
+6 more
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.
+13 more
Trial Timeline
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
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Part 2, PlaceboExperimental Treatment1 Intervention
Participants will receive placebo capsules mixed with water and administered orally in Part 2 for 4 weeks.
Group II: Part 2, LinaclotideExperimental Treatment1 Intervention
Participants will receive Linaclotide capsules mixed with water and administered orally in Part 2 for 4 weeks.
Group III: Part 1, Linaclotide Dose CExperimental Treatment1 Intervention
Linaclotide Dose C capsules, mixed with water and administered orally, once daily for 4 weeks
Group IV: Part 1, Linaclotide Dose BExperimental Treatment1 Intervention
Linaclotide Dose B capsules, mixed with water and administered orally, once daily for 4 weeks
Group V: Part 1, Linaclotide Dose AExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Velocity Clinical Research Phoenix /ID# 263871Phoenix, AZ
Kindred Medical Institute - Corona /ID# 251535Corona, CA
Velocity Clinical Research Washington DC /ID# 263872Washington, United States
Velocity Clinical Research - Lafayette /ID# 263873Lafayette, LA
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
Ironwood Pharmaceuticals, Inc.Industry Sponsor
References
Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. [2022]Linaclotide (Linzess) for irritable bowel syndrome with constipation and for chronic idiopathic constipation.
Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. [2019]Linaclotide is a secretagogue that provides a combined effect on visceral pain. The European Medicines Agency has authorized its indication for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation in adults. The purpose of this review is to discuss the clinical framework for linaclotide use in our setting, the drug´s characteristics and pre-clinical development, and the clinical studies supporting its use in order to establish relevant views regarding its validity and clinical applicability. The results suggest that the only -non-severe- adverse effect associated with this drug is diarrhea. As regards effectiveness, linaclotide consistently shows favorable, significant differences in absolute risk versus placebo for all objective outcome variables described by regulatory agencies, with a combined pain and constipation response between 12.6% and 22.8% according to the variable and trial under consideration. This response is sustained and drug-related, as it goes away upon discontinuation. To conclude, linaclotide has a safety and efficacy profile that, from a clinical perspective, warrants its use for patients meeting irritable bowel syndrome and constipation criteria, with significant symptoms that cannot be relieved with other less specific measures. In the absence of predictive rules for response, it is recommended that, should the patient fail to respond, he or she should be considered not eligible for linaclotide therapy, and both indication and treatment continuity should be reserved for objective responders alone.
Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. [2017]When patients complain of recurrent functional bowel disorders consisting of alterations in intestinal transit with abdominal pain or discomfort, treatment is purely symptomatic. Increased intake of dietary fibre or use of a bulk-forming or osmotic laxative is used when constipation is the main complaint. Linaclotide, a small peptide closely related to certain toxins secreted by diarrhoea-causing strains of Escherichia coli, has been authorised in the European Union for the treatment of adults with recurrent functional bowel disorders consisting mainly of constipation. Clinical evaluation of linaclotide includes no trials versus other laxatives. It is based on two placebo-controlled trials including a total of about 1600 patients, lasting 3 and 6 months. A pooled analysis of the results obtained at 3 months showed more frequent "relief" with linaclotide than with placebo. Adverse effects included gastrointestinal disorders, with diarrhoea occurring in one in five patients. Diarrhoea was sometimes severe or prolonged. About 10% of patients discontinued linaclotide because of gastrointestinal adverse effects (diarrhoea in half of these cases). The consequences of diarrhoea can be severe, particularly in patients predisposed to fluid and electrolyte imbalances. Co-administration of other laxative substances enhances the laxative effect of linaclotide. The laxative action is likely to reduce the gastrointestinal absorption of co-administered medications. Linaclotide should be avoided during pregnancy, as there are no relevant safety data. In practice, given the absence of head-to-head comparisons with other laxatives, linaclotide is currently just another laxative with no proven advantages over existing first-line options.
Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. [2022]Oral linaclotide, a novel agonist of guanylate cylase-C, stimulates intestinal fluid secretion and transit, and decreases visceral hypersensitivity in animal studies. In healthy volunteers, linaclotide was safe, well tolerated, increased stool frequency, and decreased stool consistency and time to first bowel movement. This randomized, double-blind, placebo-controlled study evaluated the effects of oral linaclotide, 100 and 1000 microg once daily, in 36 women with constipation-predominant irritable bowel syndrome; colonic transit was normal in >50% patients.
Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States. [2017]To evaluate the effectiveness and costs of linaclotide (Linzess) versus lubiprostone (Amitiza) in the treatment of adult patients with chronic idiopathic constipation (CIC).
Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. [2022]Linaclotide (Constella®) is a synthetic 14-amino acid peptide, structurally related to guanylin and uroguanylin, that acts as a potent guanylate cyclase C receptor agonist. It is a first-in-class agent recently approved in the EU for the treatment of adult patients with moderate to severe irritable bowel syndrome with constipation (IBS-C). Linaclotide has very low oral bioavailability and acts locally in the gastrointestinal tract to stimulate fluid secretion, increase colonic transit, and reduce abdominal pain. In phase III trials, once-daily, oral linaclotide significantly increased compared with placebo the proportions of 12-week abdominal pain/discomfort responders and 12-week degree-of-relief responders (co-primary endpoints recommended by the European Medicines Agency). Linaclotide also significantly increased the proportions of responders at 26 weeks compared with placebo, and significantly improved all abdominal symptoms and measures of bowel function at 12 weeks compared with placebo. In addition, linaclotide generally improved health-related quality of life compared with placebo. Linaclotide was generally well tolerated; the most common adverse event was diarrhoea. Thus, linaclotide is a novel and effective single agent for the treatment of IBS-C in adults.
[Pharmacological and clinical profile of linaclotide (Linzess®), a novel therapeutic agent for irritable bowel syndrome with constipation and chronic constipation]. [2019]Linaclotide (Linzess® tablets 0.25 mg) is a guanylate cyclase-C (GC-C) agonist with high selectivity and binding affinity to GC-C. In Japan, linaclotide was approved for 〝irritable bowel syndrome with constipation (IBS-C)〟 in December 2016 and 〝chronic constipation (CC) (excluding constipation due to organic disease)〟 in August 2018. Non-clinical studies demonstrated that linaclotide binding to GC-C increases intracellular cyclic guanosine monophosphate (cGMP), resulting in increased fluid secretion and gastrointestinal transit. In rats with colonic hyperalgesia, but not in normal rats, linaclotide suppressed the visceral nociceptive response, mediated by increased submucosal cGMP. In clinical studies in Japan, improvements were observed in the responder rates for global assessment of IBS symptom relief, complete spontaneous bowel movements in patients with IBS-C, and the frequency of spontaneous bowel movement in patients with CC, which were maintained during long-term treatment. Additionally, abdominal bloating, which has been associated with lower quality of life (QOL) and lower satisfaction with other approved therapies, and IBS QOL were improved throughout treatment with linaclotide. Diarrhea, a consequence of linaclotide's mechanism of action, was observed during the clinical studies, but was generally controllable by decreasing the linaclotide dose. No drug resistance was observed during the clinical studies, unlike some other approved agents. These results of non-clinical and clinical studies demonstrate that linaclotide can improve constipation, various abdominal symptoms, and QOL with a favorable safety profile in patients with IBS-C and CC.
The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. [2017]Linaclotide is a novel intestinal secretagogue that is in the advanced stages of development for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation. These functional gastrointestinal disorders are highly prevalent in adults and children and often do not respond satisfactorily to available treatments. Linaclotide appears to be a promising new agent for patients who are not satisfied with currently available agents.
Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. [2018]Linaclotide is a minimally absorbed, 14-amino acid peptide used to treat patients with irritable bowel syndrome with constipation (IBS-C) or chronic constipation (CC). We performed a meta-analysis to determine the efficacy of linaclotide, compared with placebo, for patients with IBS-C or CC.