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| Name | Class |
|---|---|
| Ironwood Pharmaceuticals, Inc. | INDUSTRY |
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The primary objective of this study is to assess the potential of LINZESS® (linaclotide) treatment to induce the development of anti-drug antibodies (ADAs). The secondary objectives are to provide additional evidence supporting the long-term safety and efficacy of linaclotide in adult irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) participants and to evaluate lower doses of linaclotide.
This study includes up to a 3-week Screening Period, followed by a 52-week treatment period. Participants with CIC meeting the entry criteria received linaclotide 145 μg capsules, orally, once daily and participants with IBS-C meeting the entry criteria received linaclotide 290 μg capsules, orally, once daily. Participants with intolerable Adverse Events (AEs), following resolution of the AEs, could be randomized to receive 290 μg, 145 μg, or the lower dose of 72 μg linaclotide oral capsules for IBS-C; and 145 μg or 72 μg for CIC. Participants who experienced further intolerable AEs after the randomization could be transitioned to open-label 72 μg linaclotide.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LINZESS® 145 μg (CIC, Open Label) | Experimental | LINZESS® (linaclotide) 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period. |
|
| LINZESS® 290 μg (IBS-C, Open Label) | Experimental | LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period. |
|
| LINZESS® 290 μg (IBS-C, Double Blind) | Experimental | Following participation in the Open Label Treatment Period, LINZESS® 290 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable. |
|
| LINZESS® 145 μg (IBS-C, Double Blind) | Experimental | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable. |
|
| LINZESS® 72 μg (IBS-C, Double Blind) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linaclotide | Drug | Linaclotide capsules, orally, once daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum | Participants who met either of the following criteria: 1) treatment-induced ADA-positive (≥ 1 postbaseline ADA-positive sample) for baseline ADA negative or ADA-undetermined participants or 2) treatment-boosted ADA-positive (≥ 1 postbaseline ADA-positive sample with titer values ≥ 4-fold the baseline titer value) for baseline ADA-positive participants were reported as a ADA positive responder. | Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Participant's Assessment of Constipation Severity | Participants rated constipation severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement. | Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
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Inclusion Criteria:
A. IBS Criteria: The participant must have abdominal pain or discomfort at least 3 days per month in the 3 months before diagnosis (with symptom onset at least 6 months before diagnosis) associated with 2 or more of the following:
Improvement with defecation.
Onset associated with a change in frequency of stool.
Onset associated with a change in form (appearance) of stool. B. Stool Consistency Requirement: During the 3 months before diagnosis in the absence of laxative or enema use, the patient has hard or lumpy stools (Bristol Stool Form Scale [BSFS] score 1 or 2) with at least 25% of bowel movements (BMs) and has loose or mushy stools (BSFS 5 or 6) with <25% of BMs.
A. Participant meets 2 or more of the following criteria for 3 months before the diagnosis with symptom onset at least 6 months before diagnosis:
Straining during at least 25% of defecations.
Lumpy or hard stools in at least 25% of defecations.
Sensation of incomplete evacuation for at least 25% of defecations.
Sensation of anorectal obstruction/blockage for at least 25% of defecations.
Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor).
Fewer than 3 defecations per week. B. Loose stools are rarely present without the use of laxatives. C. Insufficient criteria for irritable bowel syndrome. (The criteria for IBS are provided in Point A under IBS Criteria, above).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wieslaw Bochenek | Allergan | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pinnacle Research Group, LLC | Anniston | Alabama | 36207 | United States | ||
| North Alabama Research Center, LLC |
826 participants received LINZESS® 145μg [CIC] and 290μg [IBS-C] in the Open Label Treatment Period. Out of 826, 114 participants were randomized in the Double-blind Treatment Period and 57 out of 114 participants received 72 μg in the Dose-reduced Open Label Treatment Period due to intolerable AEs.
828 participants were enrolled, 2 participants were enrolled but did not receive study treatment and were not included in any analysis populations.
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| ID | Title | Description |
|---|---|---|
| FG000 | LINZESS® 145 μg (CIC, Open Label) | LINZESS® 145 μg capsules, orally, once daily for up to 52 weeks for participants with chronic idiopathic constipation (CIC). If an intolerable adverse event (AE) occurred participants could be randomized to the Double-blind Treatment Period. |
| FG001 | LINZESS® 290 μg (IBS-C, Open Label) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Open-label Treatment Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 5, 2015 | Feb 5, 2019 |
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| Experimental |
Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
| LINZESS® 145 μg (CIC, Double Blind) | Experimental | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
|
| LINZESS® 72 μg (CIC, Double Blind) | Experimental | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
| LINZESS® 72 μg (CIC, Dose-reduced Open Label) | Experimental | Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with CIC. |
|
| LINZESS® 72 μg (IBS-C, Dose-reduced Open Label) | Experimental | Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with IBS-C. |
|
|
| Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C) | Participants rated IBS symptoms severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement. | Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
| Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C | Participants rated degree of relief of IBS symptoms during previous 7 days on a 7-point balanced ordinal scale where, 1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse and 7=as bad as I can imagine. Lower scores indicate greater relief. A negative change from Baseline indicates improvement. | Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
| IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C | Participants rated degree of satisfaction with the LINZESS®'s ability to relieve IBS symptoms on a 5-point ordinal scale where, 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction. | Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
| Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC) | Participants rated degree of satisfaction with LINZESS®'s ability to relieve constipation symptoms on a 5-point ordinal scale where 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction. | Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
| Number of Participants With Recurrence of Diarrhea | Participant reporting any instance of diarrhea during the Double-blind Treatment Period. | From first dose in the Double-blind Treatment Period to Week 52 |
| Number of Participants With Recurrence of Intolerable Diarrhea | Participants reporting any instance of intolerable diarrhea during the Double-blind Treatment Period (Non-responder otherwise). Only includes participants reporting intolerable diarrhea during the Open-label Treatment Period. | From first dose in the Double-blind Treatment Period to Week 52 |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAE) | An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurred after receiving the first dose of investigational product or an AE present prior to first dose but increased in severity during the Treatment Period. | From first dose of study treatment up to Week 52 |
| Time to First Recurrence of Diarrhea | Time to first recurrence of diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period. | From first dose in the Double-blind Treatment Period to Week 52 |
| Time to First Recurrence of Intolerable Diarrhea | Time to first recurrence of intolerable diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of intolerable diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period. | From first dose in the Double-blind Treatment Period to Week 52 |
| Athens |
| Alabama |
| 35611 |
| United States |
| Alliance Clinical Research | Childersburg | Alabama | 35044 | United States |
| G & L Research, LLC | Foley | Alabama | 36535 | United States |
| Radiant Research, Inc. | Chandler | Arizona | 85224 | United States |
| Radiant Research, Inc. | Scottsdale | Arizona | 85251 | United States |
| Clinical Research Institute of Arizona, LLC | Surprise | Arizona | 85374 | United States |
| Clinical Research Consortium | Tempe | Arizona | 85283 | United States |
| Desert Sun Clinical Research, LLC. | Tucson | Arizona | 85710 | United States |
| Preferred Research Partners, Inc. | Little Rock | Arkansas | 72211 | United States |
| Applied Research Center of Arkansas | Little Rock | Arkansas | 72212 | United States |
| Kindred Medical Institute for Clinical Trials, LLC | Corona | California | 92879 | United States |
| Global Clinical Trials LLC | Costa Mesa | California | 92627 | United States |
| Diagnamics Inc | Encinitas | California | 92024 | United States |
| MD Studies, Inc. | Fountain Valley | California | 92708 | United States |
| Research Center of Fresno, Inc. | Fresno | California | 93702 | United States |
| VVCRD Clinical Research | Garden Grove | California | 92845 | United States |
| Facey Medical Foundation | Mission Hills | California | 91345 | United States |
| Clinical Trials Research | Sacramento | California | 95821 | United States |
| Northern California Research | Sacramento | California | 95821 | United States |
| Artemis Institute for Clinical Research | San Diego | California | 92103 | United States |
| Precision Research Institute | San Diego | California | 92114 | United States |
| Empire Clinical Research | Upland | California | 91786 | United States |
| Lynn Institute of Denver | Denver | Colorado | 80246 | United States |
| ZASA Clinical Research | Boynton Beach | Florida | 33472 | United States |
| Meridien Research | Bradenton | Florida | 34201 | United States |
| Clinical Research of Brandon LLC | Brandon | Florida | 33511 | United States |
| Clinical Physiology Associates | Fort Myers | Florida | 33912 | United States |
| Direct Helpers Research Center | Hialeah | Florida | 33012 | United States |
| Eastern Research, Inc. | Hialeah | Florida | 33013 | United States |
| Center for Advanced Gastroenterology | Maitland | Florida | 32751 | United States |
| Florida Medical Center and Research, Inc. | Miami | Florida | 33142 | United States |
| Clinical Neuroscience Solutions, Inc | Orlando | Florida | 32801 | United States |
| Accord Clinical Research | Port Orange | Florida | 32129 | United States |
| Meridien Research | St. Petersburg | Florida | 33709 | United States |
| River Birch Research Alliance, LLC | Blue Ridge | Georgia | 30513 | United States |
| North Georgia Clinical Research | Woodstock | Georgia | 30189 | United States |
| Northwest Clinical Trials | Boise | Idaho | 83704 | United States |
| Rockford Gastroenterology Associates | Rockford | Illinois | 611047 | United States |
| Iowa Digestive Center, PC | Clive | Iowa | 50325 | United States |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| Integrated Clinical Trial Services, Inc. | West Des Moines | Iowa | 50265 | United States |
| Heartland Research Associates, LLC | Newton | Kansas | 67114 | United States |
| Health Science Research Center | Pratt | Kansas | 67124 | United States |
| Heartland Research Associates, LLC | Wichita | Kansas | 67205 | United States |
| Heartland Research Associates, LLC | Wichita | Kansas | 67207 | United States |
| KAMP Medical Research Inc | Natchitoches | Louisiana | 71457 | United States |
| Coastal Research Associates, Inc. | South Weymouth | Massachusetts | 02190 | United States |
| Bay State Clinical Trials, Inc. | Watertown | Massachusetts | 02472 | United States |
| Aa Mrc Llc | Flint | Michigan | 48503 | United States |
| Beyer Research | Kalamazoo | Michigan | 49009 | United States |
| The Center for Clinical Trials, Inc. | Biloxi | Mississippi | 39531 | United States |
| Sundance Clinical Research, LLC | St Louis | Missouri | 63141 | United States |
| Digestive Health Associates | Reno | Nevada | 89511 | United States |
| Albuquerque Clinical Trials | Albuquerque | New Mexico | 87102 | United States |
| Lovelace Scientific Resources, Inc. | Albuquerque | New Mexico | 87108 | United States |
| Drug Trials America | Hartsdale | New York | 10530 | United States |
| Manhattan Medical Research Practice PLLC | New York | New York | 10016 | United States |
| DiGiovanna Institute for Medical Education & Research | North Massapequa | New York | 11758-1802 | United States |
| UNC Health Care, University of North Carolina Medical Center, Memorial Hospital | Chapel Hill | North Carolina | 27514 | United States |
| PharmQuest | Greensboro | North Carolina | 27408 | United States |
| Northstate Clinical Research | Lenoir | North Carolina | 38645 | United States |
| Digestive Health Specialists, PA | Winston-Salem | North Carolina | 27103 | United States |
| New Horizons Clinical Research | Cincinnati | Ohio | 45242 | United States |
| Clinical Inquest Center LTD | Dayton | Ohio | 45419 | United States |
| Dayton Gastroenterology, Inc. | Dayton | Ohio | 45440 | United States |
| IPS Research Company | Oklahoma City | Oklahoma | 73103 | United States |
| The Clinical Trial Center, LLC | Jenkintown | Pennsylvania | 19046 | United States |
| Temple University | Philadelphia | Pennsylvania | 19140 | United States |
| Preferred Primary Care Physicians, INC | Pittsburgh | Pennsylvania | 15236 | United States |
| Montgomery Medical, Inc. | Smithfield | Pennsylvania | 15478 | United States |
| Partners In Clinical Research | Cumberland | Rhode Island | 02864 | United States |
| Greenville Pharmaceutical Research, Inc. | Greenville | South Carolina | 29615 | United States |
| Radiant Research, Inc. | Greer | South Carolina | 29651 | United States |
| Clinical Neuroscience Solutions, Inc. | Memphis | Tennessee | 38119 | United States |
| Houston Endoscopy & Research Center | Houston | Texas | 77079 | United States |
| Research Across America | Plano | Texas | 75093 | United States |
| Sun Research Institute | San Antonio | Texas | 78125 | United States |
| Charlottesville Medical Research Center, LLC | Charlottesville | Virginia | 22911 | United States |
LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with irritable bowel syndrome with constipation (IBS-C). If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period. |
| FG002 | LINZESS® 290 μg (IBS-C, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 290 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable. |
| FG003 | LINZESS® 145 μg (IBS-C, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable. |
| FG004 | LINZESS® 72 μg (IBS-C, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
| FG005 | LINZESS® 145 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
| FG006 | LINZESS® 72 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
| FG007 | LINZESS® 72 μg (CIC, Dose-reduced Open Label) | Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with CIC. |
| FG008 | LINZESS® 72 μg (IBS-C, Dose-reduced Open Label) | Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with IBS-C. |
| COMPLETED | Out of 384 participants who discontinued, 114 continued to Double-blind Treatment Period. |
|
| NOT COMPLETED |
|
|
| Double-blind Treatment Period |
|
|
| Dose-reduced Open Label Treatment Period |
|
|
Safety population included all participants in the screened population (all participants who had signed an informed consent form (ICF) for the study and received a patient identification number) who received ≥ 1 administration of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | LINZESS® 145 μg (CIC, Open Label) | LINZESS® 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period. |
| BG001 | LINZESS® 290 μg (IBS-C, Open Label) | LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum | Participants who met either of the following criteria: 1) treatment-induced ADA-positive (≥ 1 postbaseline ADA-positive sample) for baseline ADA negative or ADA-undetermined participants or 2) treatment-boosted ADA-positive (≥ 1 postbaseline ADA-positive sample with titer values ≥ 4-fold the baseline titer value) for baseline ADA-positive participants were reported as a ADA positive responder. | Safety population included all participants in the screened population (all participants who had signed an informed consent form (ICF) for the study and received a patient identification number) who received ≥ 1 administration of study treatment. Participants with ≥ 1 assessable postbaseline sample were analyzed (ADA-undetermined excluded). | Posted | Count of Participants | Participants | Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks) |
|
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| |||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Participant's Assessment of Constipation Severity | Participants rated constipation severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement. | Intent to Treat (ITT) population included all participants in the safety population who had ≥ 1 postbaseline assessment for any efficacy or health outcomes parameter. Number analyzed were the participants with analysis values at both baseline and postbaseline during the specified time period. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C) | Participants rated IBS symptoms severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement. | ITT population consisted of all participants in the safety population who had ≥ 1 postbaseline assessment for any efficacy or health outcomes parameter. Number analyzed were the participants with analysis values at both baseline and postbaseline during the specified time period. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
|
| |||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C | Participants rated degree of relief of IBS symptoms during previous 7 days on a 7-point balanced ordinal scale where, 1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse and 7=as bad as I can imagine. Lower scores indicate greater relief. A negative change from Baseline indicates improvement. | Intent-to-treat (ITT) population included all participants in the safety population who had ≥ 1 postbaseline assessment for any efficacy or health outcomes parameter. Number analyzed were the participants with analysis values at both baseline and postbaseline during the specified time period. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
|
| |||||||||||||||||||||||||||||
| Secondary | IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C | Participants rated degree of satisfaction with the LINZESS®'s ability to relieve IBS symptoms on a 5-point ordinal scale where, 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction. | ITT population included all participants in the safety population who had ≥ 1 postbaseline assessment for any efficacy or health outcomes parameter. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
|
| |||||||||||||||||||||||||||||
| Secondary | Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC) | Participants rated degree of satisfaction with LINZESS®'s ability to relieve constipation symptoms on a 5-point ordinal scale where 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction. | ITT population consisted of all participants in the safety population who had ≥ 1 postbaseline assessment for any efficacy or health outcomes parameter. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period) |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Recurrence of Diarrhea | Participant reporting any instance of diarrhea during the Double-blind Treatment Period. | Double-blind safety population consisted of all participants in the randomized population who received ≥ 1 dose of study treatment during the Double-blind Treatment Period. Number of Participants Analyzed were the participants reporting intolerable diarrhea during the Open-label Treatment Period. | Posted | Count of Participants | Participants | From first dose in the Double-blind Treatment Period to Week 52 |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Recurrence of Intolerable Diarrhea | Participants reporting any instance of intolerable diarrhea during the Double-blind Treatment Period (Non-responder otherwise). Only includes participants reporting intolerable diarrhea during the Open-label Treatment Period. | Double-blind safety population consisted of all participants in the randomized population who received ≥ 1 dose of study treatment during the Double-blind Treatment Period. Number of Participants Analyzed were the participants reporting intolerable diarrhea during the Open-label Treatment Period. | Posted | Count of Participants | Participants | From first dose in the Double-blind Treatment Period to Week 52 |
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Treatment Emergent Adverse Events (TEAE) | An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurred after receiving the first dose of investigational product or an AE present prior to first dose but increased in severity during the Treatment Period. | Safety population included all participants in the screened population who received ≥ 1 administration of study treatment. | Posted | Number | percentage of participants | From first dose of study treatment up to Week 52 |
| |||||||||||||||||||||||||||||||
| Secondary | Time to First Recurrence of Diarrhea | Time to first recurrence of diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period. | Double-blind safety population consisted of all participants in the randomized population who received ≥ 1 dose of study treatment during the Double-blind Treatment Period. Number of Participants Analyzed were the participants reporting intolerable diarrhea during the Open-label Treatment Period. | Posted | Median | 95% Confidence Interval | days | From first dose in the Double-blind Treatment Period to Week 52 |
| ||||||||||||||||||||||||||||||
| Secondary | Time to First Recurrence of Intolerable Diarrhea | Time to first recurrence of intolerable diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of intolerable diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period. | Double-blind safety population consisted of all participants in the randomized population who received ≥ 1 dose of study treatment during the Double-blind Treatment Period. Number of Participants Analyzed were the participants reporting intolerable diarrhea during the Open-label Treatment Period. | Posted | Median | 95% Confidence Interval | days | From first dose in the Double-blind Treatment Period to Week 52 |
|
From first dose of study treatment up to 1 day post last dose for non-serious adverse events and up to 30 days post last dose of study treatment for serious adverse events (Up to 56 Weeks)
Adverse Events were monitored/assessed according to indication (CIC and IBS-C), irrespective of the dose level, and cannot be reported for each dose separately.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LINZESS® 145 μg (CIC) | LINZESS® 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an Intolerable AE occurred participants could be randomized to the Double-blind Treatment Period (145 μg or 72 μg) or entered the Dose-reduced 72 μg Open Label Period. | 1 | 508 | 16 | 508 | 133 | 508 |
| EG001 | LINZESS® 290 μg (IBS-C) | LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period (290 μg, 145 μg or 72 μg) or entered the Dose-reduced 72 μg Open Label Period. | 0 | 318 | 6 | 318 | 122 | 318 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Thyroid mass | Endocrine disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Peptic ulcer | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Allergy to venom | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Fibrin D dimer increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hemiplegic migraine | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Accelerated hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area, Head | Allergan | 714-246-4500 | clinicaltrials@allergan.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 23, 2018 | Feb 5, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C523483 | linaclotide |
Not provided
Not provided
Not provided
| Lack of Efficacy |
|
| Withdrawal of Consent |
|
| Lost to Follow-up |
|
| Non-compliance with Study Drug |
|
| Lack of Efficacy |
|
| Withdrawal of Consent |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| Non-compliance with Study Drug |
|
| Other Miscellaneous Reasons |
|
| >=40 to <65 years |
|
| >=65 years |
|
| Male |
|
| Black or African American |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Native Hawaiian or Other Pacific Islander |
|
| Multiple Races |
|
| Not Hispanic or Latino |
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
|
Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable.
| OG003 | LINZESS® 145 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
| OG004 | LINZESS® 72 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
|
|
| LINZESS® 72 μg (IBS-C, Double Blind) |
Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
| OG003 | LINZESS® 145 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
| OG004 | LINZESS® 72 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
|
|
|
|
| OG002 | LINZESS® 72 μg (IBS-C, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
| OG003 | LINZESS® 145 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
| OG004 | LINZESS® 72 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
|
|
| OG002 | LINZESS® 72 μg (IBS-C, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
| OG003 | LINZESS® 145 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable. |
| OG004 | LINZESS® 72 μg (CIC, Double Blind) | Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable. |
|
|
|