12-Week Study of Plecanatide for CIC (The CIC3 Study)

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01982240
• Collaborator: (none)
• Enrollment: 1,394
• Locations: 189
• Arms: 4
• Duration (Months): 19
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to confirm that the investigational medication, plecanatide, is safe and effective in treating chronic idiopathic constipation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Idiopathic Constipation	Drug: Plecanatide; Drug: Placebo; Drug: Bisacodyl	Phase 3

Detailed Description

This is a randomized, 12-week, double-blind, placebo-controlled, study in approximately 1350 adult male and female patients with CIC comparing 2 doses of plecanatide to placebo. The study will be conducted at approximately 180 clinical study sites in the United States (US) and Canada. The primary objective of the study is to evaluate the efficacy and safety of 3.0 and 6.0 mg of plecanatide administered once daily (QD) for 12 weeks in a population of patients with CIC. The study population will include only patients without other causes of constipation or other chronic conditions that could interfere with study assessments. Patients may not take laxatives (with the exception of the study-provided rescue medication, bisacodyl 5mg tablets), or a number of prohibited drugs that are known to cause constipation or diarrhea, during study participation.

There are 6 scheduled study visits, including the screening and follow-up visits. The planned duration of participation in this study will be 112 days and up to 155 days, with washout and all visit windows considered.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1394 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic Constipation (The CIC3 Study)
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Plecanatide 3.0 mg Plecanatide tablets 3.0 mg QD for 12 weeks	Drug: Plecanatide; Plecanatide tablets QD for 12 weeks; Other Names: Trulance
Active Comparator: Plecanatide 6.0 mg Plecanatide tablets 6.0 mg QD for 12 weeks	Drug: Plecanatide; Plecanatide tablets QD for 12 weeks; Other Names: Trulance
Placebo Comparator: Placebo Matching placebo tablets QD for 12 weeks	Drug: Placebo; Matching placebo tablets QD for 12 weeks; Other Names: Trulance placebo
Other: Bisacodyl Rescue medication	Drug: Bisacodyl; Rescue medication; Other Names: Dulcolax

Outcome Measures

Primary Outcome Measures

1. Number of Durable Overall CSBM Responders , Mean Replacement Approach [12-week Treatment Period]

   A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, included at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation.

Secondary Outcome Measures

1. Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach [12-Week Treatment Period]

   A Complete Spontaneous Bowel Movement (CSBM) was a Bowel Movement (BM) that occurred in the absence of laxative use within 24 hours of the BM and the patient reported a feeling of complete evacuation. A weekly responder had 3 or more CSBMs and an increase of at least one CSBM from baseline in the same week.

2. Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach [12-Week Treatment Period]

   The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was assessed. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly SBM totals were derived from the daily diary entries reported during the Treatment Period in the BM and Symptom Diary.

3. Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach [12-Week Treatment Period]

   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. = separate hard lumps like nuts (difficult to pass) = sausage shaped but lumpy = like a sausage but with cracks on its surface = like a sausage or snake, smooth and soft = soft blobs with clear-cut edges (passed easily) = fluffy pieces with ragged edges, a mushy stool = watery, no solid pieces (entirely liquid)

4. Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach [12-Week Treatment Period]

   Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly average straining score was derived from the straining scores reported during the Treatment Period in the Daily Symptom Diary. The severity of straining during bowel movements was assessed on a 5-point Likert scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female aged 18-80, inclusive

• Meets modified Rome III criteria for functional chronic idiopathic constipation for at least 3 months with symptom onset for at least 6 months

• Completed a colonoscopy in accordance with AGA colon cancer screening guidelines (5 years), with no clinically significant findings

• Willing to maintain a stable diet during the study

Exclusion Criteria:

• Loose stool (mushy) or watery (Bristol score 6 or 7) stool in the absence of any laxative or prohibited medicine for > 25% of BMs during the 3 months prior to screening visit OR during the 14 day pre-treatment assessment

• Active peptic ulcer disease, diabetes or hypertension not adequately treated or not stable

• History of cathartic colon, laxative, enema abuse, or ischemic colitis

• Fecal impaction within 3 months of screening

• Patient has had /has any: diseases or conditions associated with constipation (GI or CNS), structural abnormality of the GI tract or gastric bypass surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, anal fissures or any disease or condition that can affect GI motility or defecation or can be associated with abdominal pain

• Unexplained and clinically significant "alarm symptoms" including lower GI bleeding, iron-deficiency anemia, weight loss or systemic signs of infection or colitis

• Major surgery, stroke or MI within 60 days of screening

• Participated in a previous plecanatide clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Synergy Research Site	Birmingham	Alabama	United States	35242
2	Synergy Research Site	Dothan	Alabama	United States	36305
3	Synergy Research Site	Gulf Shores	Alabama	United States	36542
4	Synergy Research Site	Huntsville	Alabama	United States	35801
5	Synergy Research Site	Mobile	Alabama	United States	36695
6	Synergy Research Site	Mesa	Arizona	United States	85206
7	Synergy Research Site	Phoenix	Arizona	United States	85018
8	Synergy Research Site	Phoenix	Arizona	United States	85023
9	Synergy Research Site	Tempe	Arizona	United States	85283
10	Synergy Research Site	Tucson	Arizona	United States	85712
11	Synergy Research Site	Hot Springs	Arkansas	United States	71913
12	Synergy Research Site	Little Rock	Arkansas	United States	72211
13	Synergy Research Site	North Little Rock	Arkansas	United States	72117
14	Synergy Research Site	Anaheim	California	United States	92801
15	Synergy Research Site	Anaheim	California	United States	92804
16	Synergy Research Site	Carlsbad	California	United States	92008
17	Synergy Research Site	Cerritos	California	United States	90703
18	Synergy Research Site	Chula Vista	California	United States	91910
19	Synergy Research Site	El Cajon	California	United States	92020
20	Synergy Research Site	Encinitas	California	United States	92024
21	Synergy Research Site	Encino	California	United States	91436
22	Synergy Research Site	Fountain Valley	California	United States	92708
23	Synergy Research Site	Fresno	California	United States	93726
24	Synergy Research Site	Hawaiian Gardens	California	United States	90716
25	Synergy Research Site	Lancaster	California	United States	93534
26	Synergy Research Site	Long Beach	California	United States	90806
27	Synergy Research Site	Los Angeles	California	United States	90015
28	Synergy Research Site	Los Angeles	California	United States	90045
29	Synergy Research Site	Los Angeles	California	United States	90067
30	Synergy Research Site	Mission Hills	California	United States	91345
31	Synergy Research Site	Murrieta	California	United States	92562
32	Synergy Research Site	North Hollywood	California	United States	91606
33	Synergy Research Site	Oceanside	California	United States	92054
34	Synergy Research Site	Oxnard	California	United States	93030
35	Synergy Research Site	Pasadena	California	United States	91105
36	Synergy Research Site	Poway	California	United States	92064
37	Synergy Research Site	Sacramento	California	United States	95816
38	Synergy Research Site	San Diego	California	United States	92101
39	Synergy Research Site	San Diego	California	United States	92103
40	Synergy Research Site	San Diego	California	United States	92108
41	Synergy Research Site	San Diego	California	United States	92114
42	Synergy Research Site	Thousand Oaks	California	United States	91360
43	Synergy Research Site	Colorado Springs	Colorado	United States	80907
44	Synergy Research Site	Colorado Springs	Colorado	United States	80909
45	Synergy Research Site	Denver	Colorado	United States	80218
46	Synergy Research Site	Denver	Colorado	United States	80220
47	Synergy Research Site	Denver	Colorado	United States	80246
48	Synergy Research Site	Littleton	Colorado	United States	80120
49	Synergy Research Site	Bristol	Connecticut	United States	06010
50	Synergy Research Site	Danbury	Connecticut	United States	06810
51	Synergy Research Site	Waterbury	Connecticut	United States	06708
52	Synergy Research Site	Boynton Beach	Florida	United States	33426
53	Synergy Research Site	Clearwater	Florida	United States	33759
54	Synergy Research Site	DeLand	Florida	United States	32720
55	Synergy Research Site	Fort Lauderdale	Florida	United States	33306
56	Synergy Research Site	Fort Lauderdale	Florida	United States	33308
57	Synergy Research Site	Hialeah	Florida	United States	33012
58	Synergy Research Site	Jupiter	Florida	United States	33458
59	Synergy Research Site	Lakeland	Florida	United States	33805
60	Synergy Research Site	Lynn Haven	Florida	United States	32444
61	Synergy Research Site	Miami	Florida	United States	33130
62	Synergy Research Site	Miami	Florida	United States	33165
63	Synergy Research Site	Miami	Florida	United States	33173
64	Synergy Research Site	Miami	Florida	United States	33174
65	Synergy Research Site	Miami	Florida	United States	33185
66	Synergy Research Site	Miami	Florida	United States	33186
67	Synergy Research Site	Orlando	Florida	United States	32803
68	Synergy Research Site	Orlando	Florida	United States	32806
69	Synergy Research Site	Port Orange	Florida	United States	32129
70	Synergy Research Site	Tampa	Florida	United States	33604
71	Synergy Research Site	Tampa	Florida	United States	33606
72	Synergy Research Site	Tampa	Florida	United States	33617
73	Synergy Research Site	Athens	Georgia	United States	30606
74	Synergy Research Site	Augusta	Georgia	United States	30912
75	Synergy Research Site	Decatur	Georgia	United States	30032
76	Synergy Research Site	Decatur	Georgia	United States	30033
77	Synergy Research Site	Johns Creek	Georgia	United States	30097
78	Synergy Research Site	Oakwood	Georgia	United States	30566
79	Synergy Research Site	Savannah	Georgia	United States	31406
80	Synergy Research Site	Smyrna	Georgia	United States	30082
81	Synergy Research Site	Evanston	Illinois	United States	60201
82	Synergy Research Site	Clive	Iowa	United States	50325
83	Synergy Research Site	Augusta	Kansas	United States	67010
84	Synergy Research Site	Newton	Kansas	United States	67114
85	Synergy Research Site	Shawnee Mission	Kansas	United States	66218
86	Synergy Research Site	Wichita	Kansas	United States	67205
87	Synergy Research Site	Wichita	Kansas	United States	67207
88	Synergy Research Site	Lexington	Kentucky	United States	40503
89	Synergy Research Site	Lexington	Kentucky	United States	40504
90	Synergy Research Site	Bastrop	Louisiana	United States	71220
91	Synergy Research Site	Marrero	Louisiana	United States	70072
92	Synergy Research Site	Metairie	Louisiana	United States	70006
93	Synergy Research Site	New Orleans	Louisiana	United States	70115
94	Synergy Research Site	New Orleans	Louisiana	United States	70119
95	Synergy Research Site	Shreveport	Louisiana	United States	71103
96	Synergy Research Site	Chevy Chase	Maryland	United States	20815
97	Synergy Research Site	Boston	Massachusetts	United States	02131
98	Synergy Research Site	Brockton	Massachusetts	United States	02302
99	Synergy Research Site	New Bedford	Massachusetts	United States	02740
100	Synergy Research Site	Chesterfield	Michigan	United States	48047
101	Synergy Research Site	Flint	Michigan	United States	48504
102	Synergy Research Site	Rochester	Michigan	United States	48307
103	Synergy Research Site	Saginaw	Michigan	United States	48604
104	Synergy Research Site	Southfield	Michigan	United States	48034
105	Synergy Research Site	Biloxi	Mississippi	United States	39531
106	Synergy Research Site	Jackson	Mississippi	United States	39202
107	Synergy Research Site	Saint Louis	Missouri	United States	63128
108	Synergy Research Site	Omaha	Nebraska	United States	68114
109	Synergy Research Site	Henderson	Nevada	United States	89014
110	Synergy Research Site	Las Vegas	Nevada	United States	89119
111	Synergy Research Site	Las Vegas	Nevada	United States	89121
112	Synergy Research Site	Reno	Nevada	United States	89511
113	Synergy Research Site	Lebanon	New Hampshire	United States	03756
114	Synergy Research Site	Lodi	New Jersey	United States	07644
115	Synergy Research Site	Ocean City	New Jersey	United States	07712
116	Synergy Research Site	Albuquerque	New Mexico	United States	87109
117	Synergy Research Site	Brooklyn	New York	United States	11206
118	Synergy Research Site	Great Neck	New York	United States	11023
119	Synergy Research Site	North Massapequa	New York	United States	11758
120	Synergy Research Site	Cary	North Carolina	United States	27518
121	Synergy Research Site	Chapel Hill	North Carolina	United States	27599
122	Synergy Research Site	Charlotte	North Carolina	United States	28210
123	Synergy Research Site	Charlotte	North Carolina	United States	28277
124	Synergy Research Site	Greensboro	North Carolina	United States	27403
125	Synergy Research Site	Kinston	North Carolina	United States	28501
126	Synergy Research Site	Raleigh	North Carolina	United States	27612
127	Synergy Research Site	Wilmington	North Carolina	United States	28401
128	Synergy Research Site	Winston-Salem	North Carolina	United States	27103
129	Synergy Research Site	Fargo	North Dakota	United States	58103
130	Synergy Research Site	Beavercreek	Ohio	United States	45432
131	Synergy Research Site	Centerville	Ohio	United States	45459
132	Synergy Research Site	Cincinnati	Ohio	United States	45246
133	Synergy Research Site	Hilliard	Ohio	United States	43026
134	Synergy Research Site	Huber Heights	Ohio	United States	45424
135	Synergy Research Site	Maumee	Ohio	United States	43537
136	Synergy Research Site	Mentor	Ohio	United States	44060
137	Synergy Research Site	Oakwood	Ohio	United States	45419
138	Synergy Research Site	Stow	Ohio	United States	44224
139	Synergy Research Site	Norman	Oklahoma	United States	73071
140	Synergy Research Site	Oklahoma City	Oklahoma	United States	73102
141	Synergy Research Site	Limerick	Pennsylvania	United States	19468
142	Synergy Research Site	Philadelphia	Pennsylvania	United States	19152
143	Synergy Research Site	Smithfield	Pennsylvania	United States	15478
144	Synergy Research Site	Yardley	Pennsylvania	United States	19067
145	Synergy Research Site	Anderson	South Carolina	United States	29621
146	Synergy Research Site	Charleston	South Carolina	United States	28406
147	Synergy Research Site	Columbia	South Carolina	United States	29204
148	Synergy Research Site	Chattanooga	Tennessee	United States	37421
149	Synergy Research Site	Jackson	Tennessee	United States	38305
150	Synergy Research Site	Nashville	Tennessee	United States	37205
151	Synergy Research Site	New Tazewell	Tennessee	United States	37825
152	Synergy Research Site	Austin	Texas	United States	78745
153	Synergy Research Site	Dallas	Texas	United States	75230
154	Synergy Research Site	Dallas	Texas	United States	75234
155	Synergy Research Site	Houston	Texas	United States	77043
156	Synergy Research Site	Houston	Texas	United States	77062
157	Synergy Research Site	Houston	Texas	United States	77070
158	Synergy Research Site	Houston	Texas	United States	77090
159	Synergy Research Site	Killeen	Texas	United States	76543
160	Synergy Research Site	Plano	Texas	United States	75093
161	Synergy Research Site	San Angelo	Texas	United States	76904
162	Synergy Research Site	San Antonio	Texas	United States	78209
163	Synergy Research Site	San Antonio	Texas	United States	78258
164	Synergy Research Site	Sugar Land	Texas	United States	77479
165	Synergy Research Site	Logan	Utah	United States	84341
166	Synergy Research Site	Saint George	Utah	United States	84790
167	Synergy Research Site	Salt Lake City	Utah	United States	84124
168	Synergy Research Site	Christiansburg	Virginia	United States	24073
169	Synergy Research Site	Henrico	Virginia	United States	23233
170	Synergy Research Site	Lynchburg	Virginia	United States	24502
171	Synergy Research Site	Norfolk	Virginia	United States	23502
172	Synergy Research Site	Norfolk	Virginia	United States	23507
173	Synergy Research Site	Richmond	Virginia	United States	23294
174	Synergy Research Site	Virginia Beach	Virginia	United States	23455
175	Synergy Research Site	Seattle	Washington	United States	98105
176	Synergy Research Site	Tacoma	Washington	United States	98405
177	Synergy Research Site	Wauwatosa	Wisconsin	United States	53226
178	Synergy Research Site	Kelowna	British Columbia	Canada	V1Y 1Z9
179	Synergy Research Site	Bridgewater	Nova Scotia	Canada	B4V 3N2
180	Synergy Research Site	Brampton	Ontario	Canada	L6T 0G1
181	Synergy Research Site	Cambridge	Ontario	Canada	N1S 2M6
182	Synergy Research Site	London	Ontario	Canada	N5Y 5K7
183	Synergy Research Site	Oshawa	Ontario	Canada	L1H 1B9
184	Synergy Research Site	Sudbury	Ontario	Canada	P3E 1H5
185	Synergy Research Site	Toronto	Ontario	Canada	M3H 5S4
186	Synergy Research Site	Toronto	Ontario	Canada	M9W 4L6
187	Synergy Research Site	Mirabel	Quebec	Canada	J7J 2K8
188	Synergy Research Site	Pointe-Claire	Quebec	Canada	H9R 4S3
189	Synergy Research Site	St-Romuald	Quebec	Canada	G6W 5M6

Sponsors and Collaborators

• Bausch Health Americas, Inc.

Investigators

• Study Director: Mary Beth Layton, Synergy Pharmaceuticals Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT01982240
• Other Study ID Numbers: SP304203-00
• First Posted: Nov 13, 2013
• Last Update Posted: Dec 26, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by Bausch Health Americas, Inc.: CIC; Constipation; Chronic Constipation; Synergy; Plecanatide
• Additional relevant MeSH terms: Constipation; Bisacodyl; Plecanatide

Study Results

Participant Flow

Pre-assignment Detail	The data are correct and approved in the NDA. 1394 randomized subj.including 69 (index and non-index) duplicate subj. The index subj (21) were duplicate appeared the first time in the study and the same subject appeared in other studies or sites were non-index duplicate (48) who were excluded in the ITT population (1346).

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks Placebo: Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide: Plecanatide tablets QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Period Title: Overall Study
STARTED	452	453	441
COMPLETED	385	384	371
NOT COMPLETED	67	69	70

Baseline Characteristics

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6.0 mg	Total
Arm/Group Description	Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks	Total of all reporting groups
Overall Participants	452	453	441	1346
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	46.4	45.0	45.1	45.5
Sex: Female, Male (Count of Participants)
Female	357 79%	368 81.2%	362 82.1%	1087 80.8%
Male	95 21%	85 18.8%	79 17.9%	259 19.2%

Outcome Measures

1. Primary Outcome

Title	Number of Durable Overall CSBM Responders , Mean Replacement Approach
Description	A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, included at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation.
Time Frame	12-week Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT (Intent-to-treat) population was used for analysis.

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6.0 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks Placebo: Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide: Plecanatide tablets QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Measure Participants	452	453	441
Count of Participants [Participants]	46 10.2%	95 21%	86 19.5%

2. Secondary Outcome

Title	Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach
Description	A Complete Spontaneous Bowel Movement (CSBM) was a Bowel Movement (BM) that occurred in the absence of laxative use within 24 hours of the BM and the patient reported a feeling of complete evacuation. A weekly responder had 3 or more CSBMs and an increase of at least one CSBM from baseline in the same week.
Time Frame	12-Week Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT (Intent-to-treat) population was used for analysis.

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6.0 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Measure Participants	452	453	441
Baseline	0.39 (0.570)	0.32 (0.514)	0.32 (0.509)
Week 12 change from baseline	1.45 (2.310)	2.68 (3.891)	2.39 (3.296)

3. Secondary Outcome

Title	Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach
Description	The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was assessed. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly SBM totals were derived from the daily diary entries reported during the Treatment Period in the BM and Symptom Diary.
Time Frame	12-Week Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT (Intent-to-treat) population was used for analysis.

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6.0 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks Placebo: Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide: Plecanatide tablets QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Measure Participants	452	453	441
Baseline	2.18 (2.032)	1.97 (1.772)	1.82 (1.824)
Week 12 change from baseline	1.37 (2.881)	3.30 (4.628)	3.24 (4.518)

4. Secondary Outcome

Title	Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach
Description	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. = separate hard lumps like nuts (difficult to pass) = sausage shaped but lumpy = like a sausage but with cracks on its surface = like a sausage or snake, smooth and soft = soft blobs with clear-cut edges (passed easily) = fluffy pieces with ragged edges, a mushy stool = watery, no solid pieces (entirely liquid)
Time Frame	12-Week Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT (Intent-to-treat) population was used for analysis.

Arm/Group Title	Placebo	Plecanatide 3.0 mg	Plecanatide 6.0 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks Placebo: Matching placebo tablets QD for 12 weeks	Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide: Plecanatide tablets QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Measure Participants	452	453	441
Baseline	2.56 (1.114)	2.52 (1.046)	2.59 (1.171)
Week 12 change from baseline	0.83 (1.246)	1.56 (1.504)	1.47 (1.584)

5. Secondary Outcome

Title	Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach
Description	Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly average straining score was derived from the straining scores reported during the Treatment Period in the Daily Symptom Diary. The severity of straining during bowel movements was assessed on a 5-point Likert scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.
Time Frame	12-Week Treatment Period

Outcome Measure Data

Analysis Population Description

The ITT (Intent-to-treat) population was used for analysis.

Arm/Group Title	Plecanatide 3.0 mg	Placebo	Plecanatide 6.0 mg
Arm/Group Description	Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide: Plecanatide tablets QD for 12 weeks	Matching placebo tablets QD for 12 weeks Placebo: Matching placebo tablets QD for 12 weeks	Plecanatide tablets 6.0 mg QD for 12 weeks
Measure Participants	453	452	441
Baseline	2.31 (0.835)	2.30 (0.842)	2.28 (0.894)
Week 12 change from baseline	-0.70 (0.967)	-0.95 (1.027)	-1.00 (1.155)

Adverse Events

Adverse Event Reporting Description	The Intent-to-treat Safety (ITT-S) population (1389) was the enrolled population (1394) who received at least one dose of study drug.
Arm/Group Title	Placebo		Plecanatide 3.0 mg		Plecanatide 6.0 mg
Arm/Group Description	Matching placebo tablets QD for 12 weeks		Plecanatide tablets 3.0 mg QD for 12 weeks		Plecanatide tablets 3.0 mg QD for 12 weeks
All Cause Mortality
	Placebo		Plecanatide 3.0 mg		Plecanatide 6.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Plecanatide 3.0 mg		Plecanatide 6.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/458 (0.9%)		6/474 (1.3%)		5/457 (1.1%)
Gastrointestinal disorders
Intestinal obstruction	0/458 (0%)	0	1/474 (0.2%)	1	1/457 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	0/458 (0%)	0	1/474 (0.2%)	1	0/457 (0%)	0
Infections and infestations
Diverticulitis	1/458 (0.2%)	1	0/474 (0%)	0	0/457 (0%)	0
Mastitis	1/458 (0.2%)	1	0/474 (0%)	0	0/457 (0%)	0
Pneumonia	1/458 (0.2%)	1	0/474 (0%)	0	0/457 (0%)	0
Gastroenteritis	0/458 (0%)	0	0/474 (0%)	0	1/457 (0.2%)	1
Staphylococcal infection	0/458 (0%)	0	0/474 (0%)	0	1/457 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/458 (0%)	0	0/474 (0%)	0	1/457 (0.2%)	1
Investigations
Aspartate aminotransferase increased	0/458 (0%)	0	1/474 (0.2%)	1	0/457 (0%)	0
Nervous system disorders
Cerebral infarction	0/458 (0%)	0	1/474 (0.2%)	1	0/457 (0%)	0
Headache	0/458 (0%)	0	0/474 (0%)	0	1/457 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/458 (0%)	0	2/474 (0.4%)	2	0/457 (0%)	0
Vascular disorders
Peripheral arterial occlusive disease	1/458 (0.2%)	1	0/474 (0%)	0	0/457 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Plecanatide 3.0 mg		Plecanatide 6.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/458 (1.7%)		38/474 (8%)		37/457 (8.1%)
Gastrointestinal disorders
Diarrhoea	6/458 (1.3%)	6	28/474 (5.9%)	28	26/457 (5.7%)	28
Infections and infestations
Sinusitis	2/458 (0.4%)	2	10/474 (2.1%)	11	0/457 (0%)	0
Nasopharyngitis	0/458 (0%)	0	0/474 (0%)	0	11/457 (2.4%)	12

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.