Chronic Constipation, Irritable Bowel Syndrome With Constipation
Conditions
Keywords
Constipation, Chronic Constipation, Irritable Bowel Syndrome With Constipation, Linaclotide
Brief summary
The objective of this study is to assess the long-term safety of linaclotide administered to patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C).
Interventions
DRUGLinaclotide
Linaclotide capsules, oral, once daily each morning at least 30 minutes before breakfast for the duration of the study.
Sponsors
Ironwood Pharmaceuticals, Inc.
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[NCT00402337\], MCP-103-202 \[NCT00460811\] * Sexually active patients of childbearing potential agree to use birth control * Females of childbearing potential must have a negative urine pregnancy test prior to dosing * Lactating females must agree not to breastfeed * Patient must meet protocol criteria for CC or IBS-C
Exclusion criteria
* Patient must not use protocol-defined prohibited medicine * Patient is planning to receive an investigational drug at any time during the study * Patient has an unresolved AE or a clinically significant finding on a physical examination, 12-lead ECG, or clinical laboratory test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | Up to 78 weeks for AEs; within 30 days of last dose of study drug (up to 82 weeks) for serious AEs. | 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). |
Countries
Canada, United States
Participant flow
Pre-assignment details
Of the 1559 enrolled participants, all but 5 also received study drug, leading to an overall safety population of 1554 participants.
Participants by arm
| Arm | Count |
|---|---|
| Linaclotide 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 adverse events (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. | 1,554 |
| Total | 1,554 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 203 |
| Overall Study | Consent Withdrawn | 202 |
| Overall Study | Insufficient Therapeutic Response | 100 |
| Overall Study | Lost to Follow-up | 131 |
| Overall Study | Other Miscellaneous Reasons | 51 |
| Overall Study | Protocol Violation | 95 |
| Overall Study | Study Terminated by Sponsor | 2 |
Baseline characteristics
| Characteristic | Linaclotide |
|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 13.2 |
| Body Mass Index (BMI) | 28.03 kg/m^2 STANDARD_DEVIATION 6.14 |
| Height | 164.59 centimeters (cm) STANDARD_DEVIATION 8.05 |
| Race/Ethnicity, Customized African American | 312 Participants |
| Race/Ethnicity, Customized Hispanic | 192 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 1362 Participants |
| Race/Ethnicity, Customized Other | 45 Participants |
| Race/Ethnicity, Customized White | 1197 Participants |
| Sex: Female, Male Female | 1414 Participants |
| Sex: Female, Male Male | 140 Participants |
| Weight | 76.02 kilogram (kg) STANDARD_DEVIATION 17.85 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 267 / 523 | 510 / 1,032 |
| serious Total, serious adverse events | 31 / 523 | 57 / 1,032 |
Outcome results
Primary
Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
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).
Time frame: Up to 78 weeks for AEs; within 30 days of last dose of study drug (up to 82 weeks) for serious AEs.
Population: The analysis population consisted of participants in the Enrolled Population who received at least 1 dose of the open-label investigational product. It was identified that 1 participant enrolled twice in the study under 2 ID numbers; this participant is included in both the IBS-C and CC Safety Populations, leading to an analyzed population of 1555.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Linaclotide (CC) | Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | 399 Participants |
| Linaclotide (IBS-C) | Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) | 748 Participants |