– Trial designed to more comprehensively evaluate the effect of linaclotide 290 mcg on bothersome abdominal symptoms, including bloating, discomfort and pain, associated with IBS-C –
“There are an estimated 13 million adult IBS-C patients in the U.S., and
more than two thirds of them report suffering from symptoms such as
abdominal bloating and discomfort at least once per week. These symptoms
are often a primary complaint and reason for patients seeking care,”
The randomized, double-blind, placebo-controlled, parallel-group study
aims to enroll approximately 600 adult IBS-C patients in
The primary efficacy endpoint is change from baseline in abdominal score based on daily patient assessments of abdominal bloating, discomfort, and pain at their worst, as reported on an 11-point numerical rating scale. Additional endpoints include change from baseline in spontaneous bowel movement (SBM) frequency, complete spontaneous bowel movement (CSBM) frequency, stool consistency, and straining.
The clinical trial is being conducted jointly by
Linaclotide is a guanylate cyclase‐C (GC‐C) agonist that binds to the
GC-C receptor locally, within the intestinal epithelium. Linaclotide is
Important Safety Information
|WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS|
LINZESS is contraindicated in patients less than 6 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. Use of LINZESS should be avoided in patients 6 years to less than 18 years of age. The safety and effectiveness of LINZESS has not been established in patients less than 18 years of age.
LINZESS is contraindicated in patients less than 6 years of age due to the risk of serious dehydration.
LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
LINZESS is contraindicated in patients less than 6 years of age. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences.
Use of LINZESS should be avoided in pediatric patients 6 to less than 18 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 years to less than 18 years of age.
Diarrhea was the most common adverse reaction in LINZESS treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS treated patients, and in < 1% of 72 mcg LINZESS treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
In IBS-C clinical trials: 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 trials of a 145 mcg dose: 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%). In a CIC clinical trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs < 1%).
Please see full Prescribing Information: http://www.allergan.com/assets/pdf/linzess_pi
This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements about the size and scope of the Phase IIIb study of linaclotide in adults with IBS-C; the design of the Phase IIIb study, the number of patients expected to be enrolled, endpoints and the data to be generated, including the impact on IBS-C symptoms; the potential for linaclotide to offer IBS-C patients relief from bothersome symptoms including abdominal bloating, abdominal discomfort, and abdominal pain; and IBS-C symptoms and the size of the potential patient population. Each forward‐looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include those related to preclinical and clinical development, manufacturing and formulation development; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; efficacy, safety and tolerability of linaclotide; decisions by regulatory and judicial authorities; the risk that we are unable to successfully commercialize linaclotide; the risk that we may never get sufficient patent protection for linaclotide or that we are not able to successfully protect such patents; the outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates; developments in the intellectual property landscape; challenges from and rights of competitors or potential competitors; the risk that our planned investments do not have the anticipated effect on our company revenues, products or product candidates; the risk that we are unable to manage our operating expenses or cash use for operations, or are unable to commercialize our products, within the guided ranges or otherwise as expected; and the risks listed under the heading "Risk Factors" and elsewhere in Ironwood's Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, and in our subsequent SEC filings. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements.
Media and Investors:
Meredith Kaya, 617-374-5082
Vice President, Investor Relations and Corporate Communications