Linaclotide is the first and only
"Abdominal pain is a key symptom of many gastrointestinal diseases,
including IBS-C. Millions of patients are impacted by abdominal pain,
and they have few prescription options," said
"With colonic release, we are seeking to peel apart the two components
of the linaclotide mechanism of action, which we believe may lead to two
product opportunities potentially addressing multiple unmet
gastrointestinal needs," said
The randomized, double-blind, placebo-controlled, multi-site Phase IIb clinical trial is expected to enroll up to 520 adult patients with IBS-C. Patients will be randomized to one of eight groups: one group receives placebo, one group receives 290 mcg linaclotide (approved formulation), three groups receive various doses of CR1 (colonic release formulation 1 at 30 mcg, 100 mcg or 300 mcg), and three groups receive various doses of CR2 (colonic release formulation 2 at 30 mcg, 100 mcg or 300 mcg). The 290 mcg approved formulation is included as a positive control for this study. All doses will be administered orally, once daily for 12 weeks. The trial is designed to assess the safety and efficacy of each linaclotide colonic release dose and formulation, including its effect on abdominal pain relief and complete spontaneous bowel movement (CSBM) frequency, as well as on other abdominal and bowel symptoms commonly experienced by IBS-C patients. The trial also aims to evaluate how the two colonic release formulations compare to each other and to the approved 290 mcg formulation of linaclotide, with the goal of identifying appropriate doses and formulations for Phase III clinical trials.
About Irritable Bowel Syndrome with Constipation
Irritable bowel syndrome with constipation (IBS-C) is a functional
gastrointestinal disorder in which individuals experience hallmark
symptoms of abdominal pain and infrequent bowel movements (less than
three times per week). While estimates vary, as many as 13 million
adults in the U.S. may suffer from IBS-C. Results derived from responses
to a web based survey commissioned by
Linaclotide is a guanylate cyclase‐C (GC‐C) agonist that is thought to
work in two ways based on nonclinical studies. Linaclotide binds to the
GC-C receptor locally, within the intestinal epithelium. Activation of
GC-C results in increased intestinal fluid secretion and accelerated
transit and a decrease in the activity of pain-sensing nerves in the
intestine. The clinical relevance of the effect on pain fibers, which is
based on nonclinical studies, has not been established. Linaclotide is
marketed by Ironwood and
Important Safety Information
WARNING: PEDIATRIC RISK
LINZESS is contraindicated in pediatric patients under 6 years of age. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. The safety and efficacy of LINZESS has not been established in pediatric patients under 18 years of age.
- LINZESS is contraindicated in pediatric patients under 6 years of age.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in children under 6 years of age. The safety and effectiveness of LINZESS in pediatric patients under 18 years of age have not been established. In neonatal mice, increased fluid secretion as a consequence of GC-C agonism resulted in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, children under 6 years of age may be more likely than older children and adults to develop significant diarrhea and its potentially serious consequences.
- Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 through 17 years of age.
- Diarrhea was the most common adverse reaction of LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. Severe diarrhea was reported in 2% of LINZESS-treated patients. The incidence of diarrhea was similar in the IBS-C and CIC populations.
- Patients should be instructed to stop LINZESS if severe diarrhea occurs and to contact their healthcare provider. The healthcare provider should consider dose suspension and rehydration.
- In IBS-C clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
- In CIC clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%).
Please see full Prescribing Information including Boxed Warning: http://www.frx.com/pi/linzess_pi.pdf
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With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives.
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