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This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in patients with IBS-C.
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in patients with IBS-C. Patients will undergo a Screening Period to determine eligibility. After completing a Screening Visit patients will undergo a 2-week Pre-Treatment assessment using the Interactive Voice Response System (IVRS) during which they will complete daily assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale- BSFS), abdominal pain or abdominal discomfort and other symptoms associated with IBS-C. Data from the two-week IVRS Pre-treatment assessment are used to define the patient's baseline from which change will be determined. Patients who meet all entry criteria will be randomized to one of five treatment groups ( 0.3mg,1.0mg,3.0mg,9mg,or Placebo) on Day 1 of the Treatment Period. Patients will take an oral dose of study drug daily (QD) for 12 weeks and continue the daily IVRS diaries (BMs, abdominal pain, other symptoms). On Weeks 2, 4, 8, and 12, patients will return to the clinic to undergo safety and efficacy assessments. For 2 weeks after completing dosing, (i.e., Post-Treatment Period), patients will continue to complete daily IVRS diaries. Patients will then return to the clinical site for a final follow-up visit (End of Study Visit). The planned duration of participation in this study will be approximately 112 days from signing of informed consent through post-treatment or 145 days if 30 day washout of a prohibited concomitant medication or stabilization of a medical condition is required before Pre-Treatment (up to 148 days, with all windows considered).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Plecanatide 0.3mg | Active Comparator | Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks |
|
| Plecanatide 1.0mg | Active Comparator | Plecanatide 1.0mg one tablet by mouth daily for 12 weeks |
|
| Plecanatide 3.0mg | Active Comparator | Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks |
|
| Plecanatide 9.0mg | Active Comparator | Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks |
|
| Placebo | Placebo Comparator | Placebo, one tablet by mouth daily for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Plecanatide | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population) | The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation. | 12 weeks Treatment Period |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population) | Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst. | 12-Week Treatment Period |
| Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip B Miner, MD | Oklahoma Foundation for Digestive Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cahaba Research | Birmingham | Alabama | 35242 | United States | ||
| Digestive Health Specialists of the Southeast |
The Enrollment number in the Protocol Section was changed from 350 to 428 participants to reflect the actual enrollment number.
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| ID | Title | Description |
|---|---|---|
| FG000 | Plecanatide 0.3mg | Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks Plecanatide |
| FG001 | Plecanatide 1.0mg | Plecanatide 1.0mg one tablet by mouth daily for 12 weeks Plecanatide |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug |
|
The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.
|
| 12-Week Treatment Period |
| Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population) | The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe | 12-Week Treatment Period |
| Dothan |
| Alabama |
| 36305 |
| United States |
| Arrowhead Family Health Center PC dba Arrowhead Health Centers | Glendale | Arizona | 85306 | United States |
| Advanced Research Associates, LLC | Glendale | Arizona | 85308 | United States |
| Elite Clinical Trials, LLC | Phoenix | Arizona | 85018 | United States |
| Genova Clinical Research, Inc. | Tucson | Arizona | 85704 | United States |
| Adobe Clinical Research, LLC | Tucson | Arizona | 85712 | United States |
| Lynn Institute of the Ozarks | Little Rock | Arkansas | 72205 | United States |
| Anaheim Clinical Trials, LLC | Anaheim | California | 92801 | United States |
| Advanced Rx Clinical Research, Inc. | Artesia | California | 90701 | United States |
| GW Research, Inc. | Chula Vista | California | 91910 | United States |
| SC Clinical Research, Inc. | Garden Grove | California | 92844 | United States |
| Grossmont Center for Clinical Research | La Mesa | California | 91942 | United States |
| Community Clinical Trials | Orange | California | 92868 | United States |
| Healthcare Partners Medical Group | Pasadena | California | 91105 | United States |
| Medical Center for Clinical Research | San Diego | California | 92108 | United States |
| Memorial Research Medical Clinic d/b/a Orange Country Research Center | Tustin | California | 92780 | United States |
| Lynn Institute of the Rockies | Colorado Springs | Colorado | 80907 | United States |
| Horizons Clinical Research Center, LLC | Denver | Colorado | 80220 | United States |
| Consultants for Clinical Research of South Florida | Boynton Beach | Florida | 33426 | United States |
| Medical Research Unlimited, LLC | Hialeah | Florida | 33012 | United States |
| Eastern Research, Inc | Hialeah | Florida | 33013 | United States |
| Health Awareness, Inc. | Jupiter | Florida | 33458 | United States |
| Jupiter Research, Inc. | Jupiter | Florida | 33458 | United States |
| MNH Surgical Center | Maitland | Florida | 32751 | United States |
| San Marcus Research Clinic, Inc. | Miami | Florida | 33015 | United States |
| Genoma Research Group, Inc. | Miami | Florida | 33165 | United States |
| Columbus Clinical Services, LLC | Miami | Florida | 33174 | United States |
| South Medical Research Group, Inc. | Miami | Florida | 33186 | United States |
| Compass Research, LLC | Orlando | Florida | 32806 | United States |
| Urology Center of Florida | Pompano Beach | Florida | 33060 | United States |
| Accord Clinical Research, LLC | Port Orange | Florida | 32129 | United States |
| Meridien Research | Tampa | Florida | 33606 | United States |
| Palm Beach Research Center | West Palm Beach | Florida | 33409 | United States |
| Clinical Research of Central Florida | Winter Haven | Florida | 33880 | United States |
| Georgia Regents University | Augusta | Georgia | 30912 | United States |
| Mount Vernon Clinical Research, LLC | Sandy Springs | Georgia | 30328 | United States |
| CTL Research | Eagle | Idaho | 83616 | United States |
| Medex Healthcare Research, Inc | Chicago | Illinois | 60602 | United States |
| Rockford Gastroenterology Associates | Rockford | Illinois | 61107 | United States |
| Heartland Research Associates, LLC | Augusta | Kansas | 67010 | United States |
| Research Integrity, LLC | Owensboro | Kentucky | 42303 | United States |
| Delta Research Partners, LLC | Bastrop | Louisiana | 71220 | United States |
| Gastroenterology Research of New Orleans | Hammond | Louisiana | 70403 | United States |
| Centex Studies, Inc. | Lake Charles | Louisiana | 70601 | United States |
| Women Under Study, LLC | New Orleans | Louisiana | 70115 | United States |
| Louisiana Research Center, LLC | Shreveport | Louisiana | 71103 | United States |
| MGG Group Co., Inc., Chevy Chase Clinical Research | Chevy Chase | Maryland | 20815 | United States |
| Boston Clinical Trials | Boston | Massachusetts | 02131 | United States |
| Novex Clinical Research, LLC | New Bedford | Massachusetts | 02740 | United States |
| Bay State Clinical Trials, Inc. | Watertown | Massachusetts | 02472 | United States |
| IHA Chelsea Family & Internal Medicine | Chelsea | Michigan | 48118 | United States |
| Clinical Research Institute of Michigan, LLC | Chesterfield | Michigan | 48047 | United States |
| Center for Digestive Health | Troy | Michigan | 48098 | United States |
| Ridgeview Research | Chaska | Minnesota | 55318 | United States |
| Prism Research | Saint Paul | Minnesota | 55114 | United States |
| The Center for Clinical Trials | Biloxi | Mississippi | 39531 | United States |
| Gastrointestinal Associates, PA | Jackson | Mississippi | 39202 | United States |
| St. Louis Center for Clinical Research | St Louis | Missouri | 63128 | United States |
| Montana Health Research Institute, Inc. | Billings | Montana | 59102 | United States |
| Internal Medical Associates of Grand Island, PC | Grand Island | Nebraska | 68803 | United States |
| Quality Clinical Research, Inc. | Omaha | Nebraska | 68114 | United States |
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| St. Luke's Hospital | New York | New York | 10025 | United States |
| Asheville Gastroenterology Associates, PA | Asheville | North Carolina | 28801 | United States |
| MediSpect Medical Research, LLC | Boone | North Carolina | 28607 | United States |
| Clinical Trials of North Carolina, LLC | Cary | North Carolina | 27518 | United States |
| Carolina Digestive Health Associates | Charlotte | North Carolina | 28210 | United States |
| On Site Clinical, LLC | Charlotte | North Carolina | 28277 | United States |
| Carolina Digestive Health Associates | Davidson | North Carolina | 28036 | United States |
| Cumberland Research Associates, LLC | Fayetteville | North Carolina | 28304 | United States |
| LeBauer Research Associates, P.A. | Greensboro | North Carolina | 27403 | United States |
| Medoff Medical / Vital re:Search | Greensboro | North Carolina | 27408 | United States |
| Wake Research Associates, LLC | Raleigh | North Carolina | 27612 | United States |
| PMG Research of Winston-Salem, LLC | Winston-Salem | North Carolina | 27103 | United States |
| Hometown Urgent Care and Occupational Health | Columbus | Ohio | 43214 | United States |
| Great Lakes Gastroenterology | Mentor | Ohio | 44060 | United States |
| Central Sooner Research | Norman | Oklahoma | 73071 | United States |
| Oklahoma Foundation for Digestive Research | Oklahoma City | Oklahoma | 73104 | United States |
| Lynn Health Science Institute | Oklahoma City | Oklahoma | 73112 | United States |
| Options Health Research, LLC | Tulsa | Oklahoma | 74104 | United States |
| Consultants in Gastroenterology | Columbia | South Carolina | 29203 | United States |
| Southeast Medical Research | North Charleston | South Carolina | 29406 | United States |
| Palmetto Clinical Research | Summerville | South Carolina | 29485 | United States |
| Chattanooga Medical Research LLC | Chattanooga | Tennessee | 37404 | United States |
| ClinSearch, LLC | Chattanooga | Tennessee | 37421 | United States |
| Franklin Gastroenterology, PLLC | Franklin | Tennessee | 37067 | United States |
| Memphis Gastroenterology Group, PC | Germantown | Tennessee | 38138 | United States |
| Associates in Gastroenterology | Hermitage | Tennessee | 37076 | United States |
| Austin Center for Clinical Research | Austin | Texas | 78756 | United States |
| DCT-AACT, LLC dba Discovery Clinical Trials | Austin | Texas | 78758 | United States |
| Texas Tech Medical Center | El Paso | Texas | 79905 | United States |
| Centex Studies, Inc. | Houston | Texas | 77062 | United States |
| North Texas Family Medicine | Plano | Texas | 75093 | United States |
| Quality Research, Inc. | San Antonio | Texas | 78209 | United States |
| Physician PrimeCare Research Institute, PLLC dba Health Texas Research Institute | San Antonio | Texas | 78228 | United States |
| Pioneer Research Solutions, Inc. | Sugar Land | Texas | 77479 | United States |
| New River Valley Research Institute | Christiansburg | Virginia | 24073 | United States |
| Blue Ridge Medical Research/Gastroenterology Associates of Central Virginia | Lynchburg | Virginia | 24502 | United States |
| FG002 | Plecanatide 3.0mg | Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks Plecanatide |
| FG003 | Plecanatide 9.0mg | Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks Plecanatide |
| FG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks Placebo |
| COMPLETED |
|
| NOT COMPLETED |
|
The Randomized Population (428 patients) in Participant Flow differs from the mITT Population (423 patients) because 1 patient was randomized and not dosed, 1 patient was dosed but had no post-baseline efficacy assessments, and 3 duplicate patient records (2 patients who were seen at 2 sites and 1 patient who was seen at 3 sites)
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| ID | Title | Description |
|---|---|---|
| BG000 | Plecanatide 0.3mg | Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks Plecanatide |
| BG001 | Plecanatide 1.0mg | Plecanatide 1.0mg one tablet by mouth daily for 12 weeks Plecanatide |
| BG002 | Plecanatide 3.0mg | Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks Plecanatide |
| BG003 | Plecanatide 9.0mg | Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks Plecanatide |
| BG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks Placebo |
| BG005 | 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 |
| |||||||||||||||
| Sex: Female, Male | 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 | Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population) | The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation. | The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints. | Posted | Least Squares Mean | Standard Error | CSBMs per week | 12 weeks Treatment Period |
|
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population) | Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst. | The mITT population included all randomized patients who received at least 1 dose of study drug and who had at least 1 post-baseline Bowel Movement (BM) assessment was the primary analysis population for efficacy endpoints. | Posted | Least Squares Mean | Standard Error | scores on a scale | 12-Week Treatment Period |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population) | The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.
| The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints. | Posted | Least Squares Mean | Standard Error | scores on a scale | 12-Week Treatment Period |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population) | The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe | The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints. | Posted | Least Squares Mean | Standard Error | score on a scale | 12-Week Treatment Period |
|
12 weeks
A total of 428 patients were randomized and received at least one dose of medication except for one patient in the 0.3 mg plecanatide group. Therefore, a total of 427 patients were included in the safety population for adverse events reporting.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Plecanatide 0.3mg | Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks Plecanatide | 1 | 85 | 18 | 85 | ||
| EG001 | Plecanatide 1.0mg | Plecanatide 1.0mg one tablet by mouth daily for 12 weeks Plecanatide | 0 | 85 | 29 | 85 | ||
| EG002 | Plecanatide 3.0mg | Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks Plecanatide | 1 | 86 | 19 | 86 | ||
| EG003 | Plecanatide 9.0mg | Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks Plecanatide | 2 | 85 | 31 | 85 | ||
| EG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks Placebo | 0 | 86 | 12 | 86 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (14.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Patrick H. Griffin | Synergy Pharmaceuticals Inc. | 212-297-0020 |
| ID | Term |
|---|---|
| C584575 | plecanatide |
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| Male |
|
| OG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks |
|
|
| OG003 | Plecanatide 9.0mg | Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks |
| OG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks |
|
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| OG004 | Placebo | Placebo, one tablet by mouth daily for 12 weeks |
|
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