Chronic Constipation, Irritable Bowel Syndrome With Constipation
Conditions
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).
Detailed description
Participants include randomization-ineligible (RI) patients from the lead-in double-blind trials MCP-103-302 (NCT00938717) or MCP-103-303 (NCT00730015), or rollover (RO) patients from the lead-in double-blind trials MCP-103-302 (NCT00938717), MCP-103-303 (NCT00730015), and from the Phase 2 double-blind studies MCP-103-004 (NCT00306748), MCP-103-005 (NCT00258193), and MCP-103-201 (NCT00402337), or MCP-103-202 (NCT00460811).
Interventions
DRUGLinaclotide
Linaclotide capsules, oral, once daily each morning at least 30 minutes before breakfast for the duration of the study.
Sponsors
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
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 MCP-103-303 or MCP-103-302 and at minimum completed the pre-treatment period or * completed one of the following studies: MCP-103-004, MCP-103-005, MCP-103-201, MCP-103-202 * 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 adverse events or a clinically significant finding on a physical examination, 12-lead electrocardiogram, or clinical laboratory test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | From first dose of open-label study drug up to 78 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were categorized as either randomization-ineligible (RI) from the lead-in double-blind trials MCP-103-302 or MCP-103-303, or rollover (RO) from lead-in double-blind trials MCP-103-302, MCP-103-303, and from Phase 2 double-blind studies MCP-103-004, MCP-103-005, and MCP-103-201, or MCP-103-202 (See Detailed Description for NCT numbers).
Pre-assignment details
A total of 1743 participants were enrolled in the study; 1725 received ≥1 dose of open-label linaclotide (included in the Overall Safety Population). One participant enrolled twice in the study under 2 ID numbers and is included as an RI participant in the CC Safety Population, and as an RO participant in the IBS-C and Overall Safety Populations.
Participants by arm
| Arm | Count |
|---|---|
| Overall Safety Population All RI and RO participants who received linaclotide 290 μg/day capsules, administered orally once daily for up to 78 weeks. 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. | 1,725 |
| Total | 1,725 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 193 |
| Overall Study | Didn't Meet Inclusion/Exclusion Criteria | 5 |
| Overall Study | Insufficient Therapeutic Response | 141 |
| Overall Study | Lost to Follow-up | 121 |
| Overall Study | Other | 61 |
| Overall Study | Protocol Violation | 48 |
| Overall Study | Withdrawal by Subject | 202 |
Baseline characteristics
| Characteristic | Overall Safety Population |
|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 13.5 |
| Sex: Female, Male Female | 1532 Participants |
| Sex: Female, Male Male | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 607 | 2 / 1,119 | 4 / 1,725 |
| other Total, other adverse events | 283 / 607 | 572 / 1,119 | 855 / 1,725 |
| serious Total, serious adverse events | 41 / 607 | 56 / 1,119 | 97 / 1,725 |
Outcome results
Primary
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
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.
Time frame: From first dose of open-label study drug up to 78 weeks
Population: Enrolled participants who received at least 1 dose of open-label study drug. It was identified that 1 participant enrolled twice in the study under 2 ID numbers; this participant is included as an RI participant in the CC Safety Population, and as an RO participant in both the IBS-C and Overall Safety Populations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CC Safety Population: Total | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 65 Participants |
| IBS-C Safety Population: Total | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 389 Participants |
| Overall Safety Population: Total | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | 454 Participants |