Phase III, Randomized, Double-Blind, Placebo-Controlled,... | NCT00765882

Status Module

Name	Class
Ironwood Pharmaceuticals, Inc.	INDUSTRY

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
1	Experimental	Linaclotide 290 micrograms	Drug: Linaclotide 290 micrograms
2	Experimental	Linaclotide 145 micrograms	Drug: Linaclotide 145 micrograms
3	Placebo Comparator	Matching placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Linaclotide 290 micrograms	Drug	Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Complete Spontaneous Bowel Movement (CSBM) Overall Responder	A 12-week CSBM overall responders was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline. A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.	Change from Baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
12-week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate	The number of CSBMs per week.	Change from Baseline to Week 12
12-Week Spontaneous Bowel Movement (SBM) Frequency Rate	A patient's 12-week spontaneous bowel movement (SBM) frequency rate was the number of SBMs per week calculated over the 12-weeks of the treatment period.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Paul F.C. Eng, PhD	Forest Laboratories	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site		Birmingham	Alabama	35205	United States
Forest Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25312449	Derived	Chang L, Lembo AJ, Lavins BJ, Shiff SJ, Hao X, Chickering JG, Jia XD, Currie MG, Kurtz CB, Johnston JM. The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials. Aliment Pharmacol Ther. 2014 Dec;40(11-12):1302-12. doi: 10.1111/apt.12985. Epub 2014 Oct 13.
21830967

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Dose matched placebo, oral administration, once per day.
FG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Dose matched placebo, oral administration, once per day.
BG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
BG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day
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
	BG00047.0± 13.5 BG00148.5± 12.3 BG00247.3± 13.3 BG003

Age, Customized

Number

participants

Title

Denominators

Categories

18 years to 64 years

Title	Measurements
	BG000188 BG001189 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000196 BG001195 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000208 BG001208 BG002

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

Complete Spontaneous Bowel Movement (CSBM) Overall Responder

A 12-week CSBM overall responders was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline.

A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation.

An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the Intent to Treat (ITT) Population. An observed-cases approach to missing postbaseline data was applied.

Posted

Number

participants

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts
Participants	OG000215 OG001213 OG002202

Title

Denominators

Categories

Responder

Title	Measurements
	OG00013 OG00134 OG00243

Nonresponder

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: There is no difference in the proportion of 12-week CSBM overall responders between patients taking the 145-μg dose and those taking placebo. The power, adjusted for multiplicity, was expected to be 90% based on study NCT00402337 (MCP-103-201) data.	Cochran-Mantel-Haenszel		0.0012	The p-value is still less than 0.05 after adjusting multiplicity using a serial gatekeeping multiple comparison procedure.	Odds Ratio (OR)	2.93			2-Sided	95	1.50	5.72				No	Superiority or Other

Secondary

12-week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate

The number of CSBMs per week.

Posted

Least Squares Mean

Standard Error

CSBM per week

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts
Participants

Secondary

12-Week Spontaneous Bowel Movement (SBM) Frequency Rate

A patient's 12-week spontaneous bowel movement (SBM) frequency rate was the number of SBMs per week calculated over the 12-weeks of the treatment period.

Posted

Least Squares Mean

Standard Error

SBM per week

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts
Participants

Secondary

12-Week Stool Consistency

The consistency of each BM was assessed using the 7-point Bristol Stool Form Scale:

= separate hard lumps like nuts [difficult to pass]
= sausage shaped but lumpy
= like a sausage but with cracks on 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]

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the ITT Population; 97 patients with no pretreatment spontaneous bowel movements were excluded from the 12-Week Stool Consistency analysis. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Secondary

12-Week Severity of Straining

Straining is measured on a 5-point scale, where a value of 1 is "not at all" and a value of 5 is "an extreme amount.

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the ITT Population; 97 Patients with no pretreatment spontaneous bowel movements were excluded from the 12-Week Severity of Straining analysis. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts

Secondary

12-Week Abdominal Discomfort

Abdominal discomfort is based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe."

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the Intent to Treat (ITT) Population. 1 additional patient without a baseline Abdominal Discomfort score was excluded from analysis in this endpoint. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts

Secondary

12-Week Bloating

Bloating was based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe".

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the ITT population; 1 additional patient without a baseline Bloating score was excluded from analysis in this endpoint. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts
Participants

Secondary

12-Week Constipation Severity

Constipation severity was based on a 5-point ordinal scale where a value of l is "none" and a value of 5 is "very severe".

A total of 633 patients were randomized to treatment and received at least 1 dose of study drug. 630 patients were included in the ITT population; 11 additional patients who dropped out prior to finishing 1 week of the trial were excluded from the Constipation Severity endpoint. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

units on a scale

Change from Baseline to Week 12

ID	Title	Description
OG000	Placebo	Dose matched placebo, oral administration, once per day.
OG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day
OG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day

Units	Counts

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Dose matched placebo, oral administration, once per day.	4	215	35	215
EG001	Linaclotide 145µg	Linaclotide, 145µg dose, oral administration, once per day	3	213	70	213
EG002	Linaclotide 290µg	Linaclotide, 290µg dose, oral administration, once per day	7	205	49	205

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0011 affected213 at risk EG0020 affected205 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Diverticulitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Drug toxicity	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0011 affected213 at risk EG0020 affected205 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Lymphoma	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Postoperative wound infection	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0010 affected213 at risk EG0021 affected205 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected215 at risk EG0011 affected213 at risk EG0020 affected205 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected215 at risk EG0010 affected213 at risk EG0020 affected205 at risk
Cellulitis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected215 at risk EG0010 affected213 at risk EG0020 affected205 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected215 at risk EG0010 affected213 at risk EG0020 affected205 at risk
Goitre	Endocrine disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected215 at risk EG0010 affected213 at risk EG0020 affected205 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected215 at risk EG00142 affected213 at risk EG00230 affected205 at risk
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected215 at risk EG00116 affected213 at risk EG00213 affected205 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00014 affected215 at risk EG00116 affected213 at risk EG0029 affected205 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected215 at risk EG00111 affected213 at risk EG00211 affected205 at risk

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