Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Linaclotide · 8 trials · 4 indications
An AE is any untoward medical occurrence in a clinical study participant administered study drug. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the medicinal product. An AE that occurred during the treatment period was defined as a TEAE if the AE was either not present at, or before, the day of the first dose of open-label study medication in this study or was present at, or before, the day of the first dose of open-label study medication in this study and increased in severity during the treatment period. AEs included abnormal clinically significant findings for clinical laboratory tests, physical examination findings, vital sign measurements and electrocardiograms (ECGs).
A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.
A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a bowel movement BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
For RI and Phase 2 RO participants, an AE that occurred during the study was considered a TEAE if it was not present before the day of the first dose of open-label study drug, or was present before the day of the first dose of open-label study drug but increased in severity on or after that day. For Phase 3 RO participants, an AE that occurred during the study was considered a TEAE if it was not present before the day of the first dose of double-blind study drug in trial MCP-103-302 or MCP-103-303, or was present before the day of the first dose of double-blind study drug in those trials but increased in severity on or after that day. Deaths and serious AEs (SAEs) are those that occurred on or after the date of the first dose of open-label study drug, and within 30 days of the date of last dose of open-label study drug.
A 12-week CSBM Overall Responder was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline. A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.
Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.
A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.
A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.
A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.
A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.
The change in the weekly normalized CSBM Rate during Weeks 1 through 12 of the Treatment Period from the weekly normalized CSBM Rate obtained during the Pretreatment Period. The CSBM rate was normalized based on the number of CSBMs occurring in that week, adjusting for differences in the duration of the week and black-out periods (time not covered due to a missed IVRS call) versus 7x24 hours.
Change in SBM frequency during Weeks 1 through 4 of the treatment period from the weekly SBM rate obtained during the pretreatment period.
| Arm | Type | Description |
|---|---|---|
| Linaclotide | EXPERIMENTAL | Linaclotide 290 μg/day capsules, administered orally once daily for up to 78 weeks in participants with either CC or IBS-C. Dose reduction to 145 μg/day was permitted at the discretion of the Investigator if a participant experienced AEs intolerable enough to prompt consideration of study withdrawal. After a temporary suspension of dosing, participants may have received either 145 μg/day or 290 μg/day of linaclotide, at the discretion of the Investigator. Subsequent dose adjustments (increases or decreases between 290 μg/day and 145 μg/day) were permitted also at the Investigator's discretion. |
| Linaclotide 290 µg | EXPERIMENTAL | Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period. |
| Placebo | PLACEBO_COMPARATOR | Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period. |
| 72 μg linaclotide | EXPERIMENTAL | 72 μg oral linaclotide, once daily for 12 weeks |
| 145 μg linaclotide | EXPERIMENTAL | 145 μg oral linaclotide, once daily for 12 weeks |
| 290 μg linaclotide | EXPERIMENTAL | - |
| Matching Placebo | PLACEBO_COMPARATOR | - |
| 30 μg linaclotide DR1 and placebo | EXPERIMENTAL | - |
| 100 μg linaclotide DR1 and placebo | EXPERIMENTAL | - |
| 300 μg linaclotide DR1 and placebo | EXPERIMENTAL | - |
| 30 μg linaclotide DR2 and placebo | EXPERIMENTAL | - |
| 100 μg linaclotide DR2 and placebo | EXPERIMENTAL | - |
| 300 μg linaclotide DR2 and placebo | EXPERIMENTAL | - |
| 290 μg linaclotide IR and placebo | EXPERIMENTAL | - |
| 72 ug linaclotide acetate | ACTIVE_COMPARATOR | - |
| 145 ug linaclotide acetate | ACTIVE_COMPARATOR | - |
| 290 ug linaclotide acetate | ACTIVE_COMPARATOR | - |
| 579 ug linaclotide acetate | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Linaclotide | DRUG | Linaclotide capsules, oral, once daily each morning at least 30 minutes before breakfast for the duration of the study. |
| Placebo | DRUG | Matching placebo oral capsule |
| Matching Placebo | DRUG | - |
| Linaclotide Acetate | DRUG | Oral, once daily |
Inclusion Criteria: * Patients must have * entered study LIN-MD 01\[NCT00765882\] or LIN-MD-31 \[NCT00948818\] and at minimum completed the pre-treatment period or * completed one of the following studies: MCP-103-004 \[NCT00306748\], MCP-103-005 \[NCT00258193\], MCP-103-201 \[NCT00402337\], M...
Linaclotide is a small molecule being developed for gastrointestinal conditions, specifically chronic idiopathic constipation, irritable bowel syndrome characterized by constipation, chronic constipation, and irritable bowel syndrome with constipation. It is administered to adult patients and is currently in clinical development.
Linaclotide is being developed by Ironwood Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker IRWD. The company is conducting clinical trials of linaclotide for gastrointestinal indications including chronic constipation and irritable bowel syndrome with constipation.
Linaclotide is in Phase 3 clinical development. It has completed three trials, including Phase 2 and Phase 3 studies, with a total enrollment of 2,922 participants. The drug remains investigational and has not been reported as approved by regulatory authorities.
Linaclotide has completed three clinical trials: NCT00460811, a Phase 2 dose-ranging study in irritable bowel syndrome with constipation; NCT00730171, a Phase 3 long-term safety study in chronic constipation or IBS-C; and NCT02559206, a Phase 2 trial in IBS-C. All trials were completed in the United States and Canada.
Linaclotide is a small molecule that targets the guanylate cyclase-C receptor in the gastrointestinal tract. By activating this receptor, it increases fluid secretion and accelerates intestinal transit, which helps relieve constipation. This mechanism underlies its use in chronic constipation and irritable bowel syndrome with constipation.
Linaclotide is also known by the brand name Linzess in some markets, though this alternative name is not provided in the available data. The drug is being studied under the name linaclotide in clinical trials for gastrointestinal conditions.