12-Week Study of Plecanatide for CIC (The National CIC3 S... | NCT02122471

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Plecanatide 3.0 mg	Experimental	Plecanatide tablets 3.0 mg QD for 12 weeks	Drug: Plecanatide
Placebo	Placebo Comparator	Matching placebo tablets QD for 12 weeks	Drug: Placebo
Plecanatide 6.0 mg	Experimental	Plecanatide tablets 6.0 mg QD for 12 weeks	Drug: Plecanatide

Name	Type	Description	Arm Group Labels	Other Names
Plecanatide	Drug		Plecanatide 3.0 mg Plecanatide 6.0 mg
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Durable Overall CSBM Responders, Mean Replacement Approach	The primary efficacy endpoint was measured by the number of durable overall CSBM responders over the 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, including 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.	12-Week Treatment Period

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach	The change from baseline in the number of Complete Spontaneous Bowel Movements (CSBMs) over the 12-week Treatment Period was analyzed. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. 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.

Eligibility Module

Name	Affiliation	Role
Mary Beth Layton	Synergy Pharmaceuticals Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Synergy Research Site		Anniston	Alabama	36207	United States
Synergy Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37332239	Derived	Cash BD, Sharma A, Walker A, Laitman AP, Chang L. Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation. Neurogastroenterol Motil. 2023 Sep;35(9):e14632. doi: 10.1111/nmo.14632. Epub 2023 Jun 18.
35086735

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Matching placebo tablets QD for 12 weeks
FG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Matching placebo tablets QD for 12 weeks
BG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks
BG002	Plecanatide 6 mg	Plecanatide tablets 6 mg QD for 12 weeks
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00057 OG00188 OG00288

Secondary

Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach

The change from baseline in the number of Complete Spontaneous Bowel Movements (CSBMs) over the 12-week Treatment Period was analyzed. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. 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.

A total of 1288 patients included in ITT-E population for secondary outcome which consisted of the randomized subjects (1410) excluding 95 duplicate subjects as described in the Participate Flow and 27 subjects eliminated from two OAI sites.

Posted

Least Squares Mean

Standard Error

CSBMs per week

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo	Matching placebo tablets QD for 12 weeks
OG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks
OG002	Plecanatide 6 mg	Plecanatide tablets 6 mg QD for 12 week

Secondary

Change From Baseline in SBMs (SBMs/Week) Over the 12-week Treatment Period, Mean Replacement Approach

The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was analyzed. 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.

Posted

Mean

Standard Deviation

SBMs per week

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo	Matching placebo tablets QD for 12 weeks
OG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks
OG002	Plecanatide 6 mg	Plecanatide tablets 6 mg QD for 12 weeks

Secondary

Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach

The change from baseline in the stool consistency score (i.e. BSFS) over the 12-week Treatment Period was analyzed. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly mean BSFS score per patient was derived from the BSFS entries reported during the Treatment Period in the Daily Symptom Diary.

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)

Posted

Mean

Standard Deviation

score on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo	Matching placebo tablets QD for 12 weeks
OG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks

Secondary

Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach

The change from baseline in the straining score over the 12-week Treatment Period was analyzed. 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo	Matching placebo tablets QD for 12 weeks
OG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks
OG002	Plecanatide 6 mg	Plecanatide tablets 6 mg QD for 12 weeks

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Matching placebo tablets QD for 12 weeks	8	466	15	466
EG001	Plecanatide 3 mg	Plecanatide tablets 3 mg QD for 12 weeks	8	467	25	467
EG002	Plecanatide 6 mg	Plecanatide tablets 6 mg QD for 12 weeks	4	469	31	469

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0020 events0 affected469 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0020 events0 affected469 at risk
Non-cardiac chest pain	General disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0020 events0 affected469 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Alanine aminotransferase increased	Investigations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0020 events0 affected469 at risk
Liver function test abnormal	Investigations	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0021 events1 affected469 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0020 events0 affected469 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected466 at risk EG0011 events1 affected467 at risk EG0021 events1 affected469 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0011 events1 affected467 at risk EG0021 events1 affected469 at risk
Arterial occlusive disease	Vascular disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected466 at risk EG0010 events0 affected467 at risk EG0020 events0 affected469 at risk
Convulsion	Nervous system disorders	MedDRA (14.1)	Systematic Assessment	EG0000 events0 affected466 at risk EG0010 events0 affected467 at risk EG0021 events1 affected469 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment		EG0006 events6 affected466 at risk EG00115 events15 affected467 at risk EG00225 events21 affected469 at risk
Headache	Nervous system disorders	MedDRA (14.1)	Systematic Assessment		EG00010 events9 affected466 at risk EG00110 events10 affected467 at risk EG00210 events10 affected469 at risk

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms