Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)

Functional Constipation Clinical Trial

— LINZESS  

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide in Pediatric Participants, Ages 6 to 17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) and of Linaclotide Versus Placebo in Pediatric Participants With Functional Constipation (FC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04026113
• Other study ID #: LIN-MD-64
• Secondary ID: 2019-001500-38
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2019
• Est. completion date: May 29, 2024

Study information

• Verified date: June 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (72 μg daily) in comparison with placebo in pediatric participants, 6 to 17 years of age, who fulfill modified Rome III Criteria for Child/Adolescent Functional Constipation (FC). The objective of LIN-MD-64 is to evaluate the safety and efficacy of 12 weeks of linaclotide therapy (145 μg or 290 μg daily) in pediatric participants, 7 to 17 years of age, who fulfill the Rome III criteria for child/adolescent Irritable Bowel Syndrome (IBS) and modified Rome III criteria for child/adolescent Functional Constipation (FC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 438
• Est. completion date: May 29, 2024
• Est. primary completion date: May 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• Male and female participants must be ages 6 to 17 years (FC participants) or ages 7 to 17 years (IBS-C participants) (inclusive) at the time the participant provides assent for the study and parent/guardian/legally authorized representative (LAR) has provided signed consent;

• Participant weighs =18 kg at the time the participant provides assent and the parent/guardian/LAR has provided signed consent;

• Participants who meet the modified Rome III criteria for Child/Adolescent FC. For at least 2 months before the Screening Visit, the participant has had 2 or fewer defecations (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) in the toilet per week.

In addition, participant meets one or more of the following criteria at least once per week for at least 2 months before the screening visit:

a. History of retentive posturing or excessive volitional stool retention; b. History of painful or hard BMs; c. History of large diameter stools that may obstruct the toilet; d. Presence of a large fecal mass in the rectum; e. At least 1 episode of fecal incontinence per week

• For IBS-C participants only: Participant meets Rome III criteria for child/adolescent IBS: At least once per week for at least 2 months before the Screening Visit, the participant experienced abdominal discomfort (an uncomfortable sensation not described as pain) or pain associated with 2 or more of the following at least 25% of the time:

1. Improvement with defecation;

2. Onset associated with a change in frequency of stool;

3. Onset associated with a change in form (appearance) of stool;

• For IBS-C participants only: Participant has an average daytime abdominal pain score of = 1 (at least "a tiny bit") during the 14 days before Visit 3;

• Participant is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol- permitted rescue medicine;

• Participant has an average of fewer than 3 SBMs per week during the 14 days before the randomization day and up to the randomization (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day). An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM;

• Participant or parent/guardian/LAR or caregiver is compliant with eDiary requirements by completing both the morning and evening assessments for 10 out of the 14 days immediately preceding the Randomization Visit;

• Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Randomization Visit prior to dosing;

• Female participants who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception;

• Participant must provide written or verbal informed assent and the parent/guardian/LAR and caregiver must provide written informed consent before the initiation of any study-specific procedures;

• Participant is able to read and/or understand the assessments in the eDiary device. If the participant is 6 to 11 years of age (FC participants) or 7 to 11 years of age (IBS-C participants) and does not meet this criterion, the interviewer-administered version of the eDiary must be used and the parent/guardian/LAR or caregiver who will be administering the interviewer-administered version of the eDiary must undergo training;

• Participant must have acquired toilet training skills.

Exclusion Criteria:

• For FC participants only: Participant meets Rome III criteria for Child/Adolescent IBS: At least once per week for at least 2 months before the Screening Visit, the participant has experienced abdominal discomfort (an uncomfortable sensation not described as pain) or pain associated with 2 or more of the following at least 25% of the time:

1. Improvement with defecation

2. Onset associated with a change in frequency of stool

3. Onset associated with a change in form (appearance) of stool;

• Participant reports having more than 1 loose, mushy stool (eDiary-recorded stool consistency of 6 on the Pediatric Bristol Stool Form Scale [p-BSFS]) or any watery stool (eDiary-recorded stool consistency of 7 on the p-BSFS) with any SBM that occurred in the absence of laxative use on the calendar day of the BM or the calendar day before the BM during the 14 days before the randomization day and up to the randomization (including the morning eDiary assessments reported before administration of first dose of double-blind study intervention on the randomization day);

• Participant has a history of non-retentive fecal incontinence;

• Participant has (a) fecal impaction at Visit 2 after failing outpatient clean-out during the Screening Period or (b) fecal impaction at Visit 3;

• Participant has required manual disimpaction any time prior to randomization;

• Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia, or any unexplained anemia, or weight loss) and systemic signs of infection or colitis, or any neoplastic process;

• Participant has clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), or clinical laboratory test as determined by the investigator based on consideration of whether the finding could represent a safety concern or a condition that would be exclusionary, could prevent the participant from performing any protocol assessments, or could confound study assessments;

• Participant has a history of drug or alcohol abuse;

• Participant has any of the following conditions:

1. Celiac disease, or positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy;

2. Cystic fibrosis;

3. Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to the Screening Visit;

4. Down's syndrome or any other chromosomal disorder;

5. Active anal fissure (Note: History of anal fissure is not an exclusion);

6. Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displaced anus);

7. Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceral myopathies, visceral neuropathies);

8. Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma);

9. Lead toxicity, hypercalcemia;

10. Neurodevelopmental disabilities (early-onset, chronic disorders that share the essential feature of a predominant disturbance in the acquisition of cognitive, motor, language, or social skills, which has a significant and continuing impact on the developmental progress of an individual) producing a cognitive delay that precludes comprehension and completion of the daily eDiary (Electronic handheld device) or other study-related questionnaires (Note: Participants are excluded if the person who will be completing the daily eDiary or other study-related questionnaires meets this criterion);

11. Inflammatory bowel disease;

12. Childhood functional abdominal pain syndrome;

13. Childhood functional abdominal pain;

14. Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study;

15. Lactose intolerance that is associated with abdominal pain or discomfort and could confound the assessments in this study;

16. History of cancer other than treated basal cell carcinoma of the skin; (Note:

Participants with a history of cancer are allowed provided that the malignancy has been in a complete remission for at least 5 years before the Randomization Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment);

17. History of diabetic neuropathy.

• Participant has an acute or chronic condition that, in the investigator's opinion, would limit the participants' ability to complete or participate in this clinical study;

• Participant has a known or suspected mechanical bowel obstruction or pseudoobstruction;

• Participant has a known allergy or sensitivity to the study intervention or its components or other medications in the same drug class.

• Participant has had surgery that meets any of the following criteria:

1. Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit;

2. Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit;

3. An appendectomy or cholecystectomy during the 60 days before the Screening Visit;

4. Other major surgery during the 30 days before the Screening Visit;

• Participant used a protocol-specified prohibited medicine before the start of the Preintervention Period or failed to meet the stable-dose requirements of certain medications;

• Participant used rescue medication on the calendar day before the Randomization Visit and on the day of the Randomization Visit until randomized;

• Participant received a study intervention during the 30 days before the Screening Visit or is planning to receive a study intervention (other than that administered during this study);

• Participant has been randomized into any clinical study in which linaclotide was a study intervention.

• The participant has a condition or is in a situation; which, in the investigator's opinion, may put the participant at significant risk, may confound the study results ,or may interfere significantly with the participant's participation in the study;

• Participants who have positive urine drug screen results for cocaine, barbiturates, opiates, or cannabinoids will be excluded from study participation;

• Female participants who are currently pregnant or nursing, or plan to become pregnant or nurse during the clinical study;

• Participant's parent/guardian/LAR or caregiver has been directly or indirectly involved in the conduct and administration of this study as an investigator, study coordinator, or other study staff member. In addition, any participant, parent/guardian/LAR or caregiver who has a first-degree family member, significant other, or relative residing with him/her directly or indirectly who is involved in this study.

Related Conditions & MeSH terms

• Constipation
• Functional Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Constipation
• Syndrome

Intervention

Drug:
• Linaclotide 72 µg (FC Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)
• Placebo (FC Participants)
Matching placebo
• Linaclotide 145 µg (IBS-C Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)
• Linaclotide 290 µg (IBS-C Participants)
Oral capsule (For participants who do not wish to take the dose as a capsule, a sprinkled dose may be prepared)

Locations

Country	Name	City	State
Belgium	Duplicate_UZ Brussel /ID# 232875	Brussels
Bulgaria	MHATSv.Ivan Rilski /ID# 232831	Kozloduy
Bulgaria	UMHAT Kanev /ID# 233102	Ruse
Bulgaria	Medical center 1 Sevlievo /ID# 232915	Sevlievo
Bulgaria	University Hospital Plovdiv /ID# 232775	Tsentar	Plovdiv
Canada	University of Alberta Hospital /ID# 233147	Edmonton	Alberta
Canada	London Health Sciences Center- University Hospital /ID# 233068	London	Ontario
Canada	Duplicate_SKDS Research Inc. /ID# 233000	Newmarket	Ontario
Canada	Bluewater Clinical Research Group Inc /ID# 232772	Sarnia	Ontario
Canada	Stouffville Medical Centre /ID# 232774	Stouffville	Ontario
Estonia	Al Mare Perearstikeskus /ID# 232879	Harjumaa
Estonia	Merelahe Family Doctors Centre /ID# 232881	Tallinn
Estonia	Kliiniliste Uuringute Keskus /ID# 232883	Tartu
Germany	Duplicate_Klinikum Kassel /ID# 233029	Kassel	Hessen
Israel	The Edith Wolfson Medical Center /ID# 233134	Ashkelon	HaDarom
Israel	Duplicate_Rambam Health Care Campus Ruth Rappaport Children's Hospital /ID# 232892	Haifa	H_efa
Israel	Hadassah Hebrew University Hospital - Ein Kerem /ID# 232865	Jerusalem	Yerushalayim
Israel	Shaare Zedek Medical Center /ID# 233092	Jerusalem	Yerushalayim
Israel	Schneider Children's Medical Center /ID# 233064	Petah Tikva	HaMerkaz
Israel	The Chaim Sheba Medical Center /ID# 232986	Ramat Gan	Tel-Aviv
Israel	The Baruch Padeh Medical Center Poriya /ID# 232889	Tiberias	HaTsafon
Italy	Sant?Andrea University Hospital /ID# 232825	Rome
Netherlands	Duplicate_Academisch Medisch Centrum /ID# 232895	Amsterdam	Noord-Holland
Netherlands	Maasstad Ziekenhuis /ID# 233003	Rotterdam
Netherlands	Isala /ID# 233031	Zwolle
Poland	Szpital Uniwersytecki Nr 1 im. dr Antoniego Jurasza /ID# 232898	Bydgoszcz	Kujawsko-pomorskie
Poland	Klinika Pediatrii Gastroenterologii Alergologii i Zywienia Dzieci GUM /ID# 232900	Gdansk
Poland	Poradnia Gastroenterologiczna /ID# 232899	Olsztyn
Poland	Korczowski Bartosz Gabinet Lekarski /ID# 232821	Rzeszow
Puerto Rico	San Juan Bautista School of Medicine /ID# 232913	Caguas
Spain	Instituto Hispalense Pediatria /ID# 232793	Sevilla
Ukraine	Communal Nonprofit Enterprise City Childrens Clinical Hospital 6 of Dnipro C /ID# 232863	Dnipro
Ukraine	Kharkiv Regional Childrens Clinical Hospital Gastroent. Centre Kharkiv Natl. Me /ID# 232867	Kharkiv
Ukraine	Municipal Nonprofit Enterprise Lviv City Children's Clinical Hospital /ID# 232851	Lviv
Ukraine	Vinnytsya National Medical University Departement of Pediatrics No.1 /ID# 232890	Vinnytsia
United Kingdom	William Harvey Hospital /ID# 232806	Ashford	Kent
United States	University of New Mexico /ID# 233011	Albuquerque	New Mexico
United States	Advanced Research Center /ID# 233121	Anaheim	California
United States	Children's Ctr Digestive, US /ID# 233070	Atlanta	Georgia
United States	Children's Healthcare of Atlanta - Ferry Rd /ID# 233015	Atlanta	Georgia
United States	Treken Primary Care /ID# 232796	Atlanta	Georgia
United States	Lynn Institute of Denver /ID# 233137	Aurora	Colorado
United States	Meridian Research - Baton Rouge /ID# 232954	Baton Rouge	Louisiana
United States	Alliance Research Institute /ID# 232754	Bell Gardens	California
United States	Central Research Associates /ID# 233124	Birmingham	Alabama
United States	River Birch Research Alliance /ID# 233122	Blue Ridge	Georgia
United States	Private Practice - Dr. Craig Spiegel /ID# 232707	Bridgeton	Missouri
United States	Advantage Clinical Trials /ID# 233117	Bronx	New York
United States	The Children's Hospital at Montefiore /ID# 232638	Bronx	New York
United States	Alliance Research Institute Llc /Id# 232637	Canoga Park	California
United States	Coastal Pediatric Research - West Ashley B /ID# 232816	Charleston	South Carolina
United States	Kindred Medical Institute, LLC /ID# 233042	Corona	California
United States	Oak Cliff Research Company LLC /ID# 232729	Dallas	Texas
United States	Dolphin Medical Research /ID# 232815	Doral	Florida
United States	Prohealth Research Center /ID# 232805	Doral	Florida
United States	Medclinical Research Partners LLC/ Foundation Pediatrics /ID# 232783	East Orange	New Jersey
United States	GI associates and Endoscopy Ce /ID# 233123	Flowood	Mississippi
United States	G & L Research, LLC /ID# 233139	Foley	Alabama
United States	Cook Children's Med. Center /ID# 233066	Fort Worth	Texas
United States	Office of Maria Ona /ID# 232700	Franklin	Virginia
United States	East Carolina University - Brody School of Medicine /ID# 233062	Greenville	North Carolina
United States	Valley Institute of Research /ID# 232674	Harlingen	Texas
United States	Amedica Research Institute Inc /ID# 232809	Hialeah	Florida
United States	HealthStar Research of Hot Springs PLLC /ID# 232757	Hot Springs	Arkansas
United States	Cullen Research /ID# 232726	Houston	Texas
United States	Pioneer Research Solutions - Houston /ID# 233006	Houston	Texas
United States	Synergy Group US LLC /ID# 232669	Houston	Texas
United States	Vilo Research Group Inc /ID# 233155	Houston	Texas
United States	Marshall University Medical Center /ID# 232952	Huntington	West Virginia
United States	The Jackson Clinic, PA /ID# 232998	Jackson	Tennessee
United States	Nemours Children's Health System /ID# 233127	Jacksonville	Florida
United States	Accellacare of Knoxville /ID# 232663	Jefferson City	Tennessee
United States	Univ Kansas Med Ctr /ID# 232645	Kansas City	Kansas
United States	Michael W. Simon, MD, PSC /ID# 232966	Lexington	Kentucky
United States	Applied Research Center of Arkansas /ID# 233135	Little Rock	Arkansas
United States	Preferred Research Partners /ID# 233023	Little Rock	Arkansas
United States	Elite Clinical Research /ID# 232801	Miami	Florida
United States	My Preferred Research LLC /ID# 233119	Miami	Florida
United States	South Miami Medical & Research Group Inc. /ID# 232803	Miami	Florida
United States	Valencia Medical & Research Center /ID# 232813	Miami	Florida
United States	MNGI Digestive Health, P. A. /ID# 232920	Minneapolis	Minnesota
United States	Synergy Group US LLC /ID# 232670	Missouri City	Texas
United States	Advanced Research for Health Improvement /ID# 233161	Naples	Florida
United States	Monroe-Carell Jr. Children's Hospital at Vanderbilt /ID# 232659	Nashville	Tennessee
United States	Columbia Univ Medical Center /ID# 233094	New York	New York
United States	Health Research of Hampton Roads, Inc. (HRHR) /ID# 233056	Newport News	Virginia
United States	Alliance for Multispecialty Research LLC /ID# 232681	Newton	Kansas
United States	IPS Research Company /ID# 233081	Oklahoma City	Oklahoma
United States	Univ Oklahoma HSC /ID# 233067	Oklahoma City	Oklahoma
United States	Nemours Children's Hospital /ID# 232919	Orlando	Florida
United States	Pediatric & Adult Research Center /ID# 232819	Orlando	Florida
United States	Oviedo Medical Research /ID# 232830	Oviedo	Florida
United States	Center for Clinical Trials LLC /ID# 232781	Paramount	California
United States	AIM Trials /ID# 232934	Plano	Texas
United States	David M. Headley, MD, P.A. /ID# 233153	Port Gibson	Mississippi
United States	Rhode Island Hospital /ID# 233112	Providence	Rhode Island
United States	Clinical Research Partners, LLC /ID# 233026	Richmond	Virginia
United States	Carilion Medical Center /ID# 232999	Roanoke	Virginia
United States	Chrysalis Clinical Research /ID# 232690	Saint George	Utah
United States	Sun Research Institute /ID# 233005	San Antonio	Texas
United States	Medical Ctr for Clin Research /ID# 233004	San Diego	California
United States	Paragon Rx Clinical Inc /ID# 232752	Santa Ana	California
United States	The Center for Clinical Trials Inc. /ID# 232755	Saraland	Alabama
United States	Frontier Clinical Research, LLC - Scottdale /ID# 233129	Scottdale	Pennsylvania
United States	Virgo Carter Pediatrics /ID# 232693	Silver Spring	Maryland
United States	Frontier Clinical Research /ID# 233116	Smithfield	Pennsylvania
United States	PMG Research of Piedmont Healthcare-Statesville /ID# 233162	Statesville	North Carolina
United States	Clinical Research Institute /ID# 232833	Stockbridge	Georgia
United States	Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 232940	Stockbridge	Georgia
United States	Clinical Trials Specialist Inc /ID# 232802	Stone Mountain	Georgia
United States	Coastal Pediatric Research - Summerville /ID# 232814	Summerville	South Carolina
United States	Duplicate_Multicare Institute for Research and Innovation /ID# 233010	Tacoma	Washington
United States	Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 232800	Union City	Georgia
United States	Children's National Medical Center /ID# 232655	Washington	District of Columbia
United States	ClinPoint Trials /ID# 232978	Waxahachie	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Estonia,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Puerto Rico,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional Constipation (FC) Participants: Change from baseline in 12-week SBM (spontaneous bowel movement) frequency rate (SBMs/week) during the study intervention period	An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) will be measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.	12 Weeks
Primary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks APS (abdominal pain and SBM) + 2 responder	A 6/12 weeks APS + 2 responder is a participant that meets the weekly APS + 2 responder criteria for at least 6 out of the 12 weeks of the intervention period. A weekly APS +2 responder is a participant who has an increase of at least 2 in the SBM weekly rate from baseline, AND a decrease of at least 30% in the mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain and BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.	12 Weeks
Secondary	Functional Constipation (FC) Participants: Change from baseline in 12-week stool consistency during the study intervention period	Stool consistency will be measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery A participant’s p-BSFS score for the study intervention period will be the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.	12 Weeks
Secondary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week SBM frequency rate (SBMs/week) during the study intervention period	An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) will be measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.	12 Weeks
Secondary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week abdominal pain during the study intervention period	Assessments of abdominal pain will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.	12 Weeks
Secondary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: Change from baseline in 12-week stool consistency during the study intervention period	Stool consistency will be measured twice daily, once in the morning and once in the evening eDiary, using the 7-point ordinal p-BSFS (pediatric Bristol Stool Form Scale: Type 1: Looks like small hard lumps or balls, like pebbles Type 2: Looks like fat sausage shape but lumpy and hard Type 3: Looks like a sausage but with cracks on it Type 4: Looks like a sausage or snake, smooth and soft Type 5: Looks like chicken nuggets, soft smooth blobs Type 6: Looks like oatmeal, fluffy mushy pieces Type 7: Looks like a milkshake, watery A participant’s p-BSFS score for the study intervention period will be the average of the non-missing p-BSFS scores from the SBMs reported by the participant during the 12-week study intervention period.	12 Weeks
Secondary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks SBM + 2 responder	Assessments of BM characteristics that determine occurrences of SBMs (ie, BM frequency and rescue medication use) will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.	12 Weeks
Secondary	Irritable Bowel Syndrome with Constipation (IBS-C) Participants: 6/12 weeks abdominal pain responder	Assessments of abdominal pain will be measured by using an eDiary completed twice daily (morning and evening) on a handheld, provisioned eDiary device.	12 Weeks