Trial of Linaclotide in Patients With Chronic Constipation | NCT00730015

Status Module

Name	Class
Forest Laboratories	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	Intervention Names
145 μg linaclotide	Experimental	Drug: Linaclotide
290 μg linaclotide	Experimental	Drug: Linaclotide
Matching Placebo	Placebo Comparator	Drug: Matching Placebo

Name	Type	Description	Arm Group Labels	Other Names
Matching Placebo	Drug	Oral, once daily	Matching Placebo
Linaclotide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Complete Spontaneous Bowel Movement (CSBM) Overall Responder	A 12-week CSBM Overall Responder 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	The number of CSBMs per week.	Change from Baseline to Week 12
12-Week Spontaneous Bowl Movement (SBM) Frequency	The number of SBMs per week.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Jeffrey M. Johnston, MD, FACP	Ironwood Pharmaceuticals, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Ironwood Investigational Site		Birmingham	Alabama	35209	United States
Ironwood Investigational 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

Arm/Group Information

ID	Title	Description
FG000	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
FG001	Linaclotide, 290μg	Linaclotide, 290μg 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

No data available

No data is available for this block.

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
BG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
BG002	Placebo	Dose matched placebo, 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
	BG00047.1± 14.2 BG00147.7± 14.2 BG00249.3± 14.3 BG003

Age, Customized

Number

Participants

Title

Denominators

Categories

18 years to 64 years

Title	Measurements
	BG000190 BG001190 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000191 BG001189 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000217 BG001217 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 Responder 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.

643 randomized patients received at least 1 dose of study drug. 642 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Units	Counts
Participants	OG000217 OG001216 OG002209

Title

Denominators

Categories

Title	Measurements
	OG00046 OG00142 OG0027

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 OG002	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 at least 90% based on study NCT00402337(MCP-103-201) data.	Cochran-Mantel-Haenszel		<0.0001	The p-value is still less than 0.05 after adjusting multiplicity using a serial gatekeeping multiple comparison procedure.	Odds Ratio (OR)	7.72			2-Sided	95	3.41	17.47				No	Superiority or Other

Secondary

12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency

The number of CSBMs per week.

643 randomized patients received at least 1 dose of study drug. 642 patients were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

CSBMs per Week

Change from Baseline to Week 12

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

Units	Counts
Participants	OG000

Secondary

12-Week Spontaneous Bowl Movement (SBM) Frequency

The number of SBMs per week.

643 randomized patients received at least 1 dose of study drug. 642 patients were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.

Posted

Least Squares Mean

Standard Error

SBMs per Week

Change from Baseline to Week 12

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

Units	Counts
Participants	OG000

Secondary

12-week Change in 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]

643 randomized patients received at least 1 dose of study drug; 642 patients were included in the ITT Population; 101 patients with no pretreatment spontaneous bowel movements were excluded from the 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Secondary

12-week Change in Severity of Straining

Severity of 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".

643 randomized patients received at least 1 dose of study drug; 642 patients were included in the ITT Population; 101 patients with no pretreatment spontaneous bowel movements were excluded from the 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Units	Counts
Participants

Secondary

12-week Change in 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."

643 randomized patients received at least 1 dose of study drug. 642 patients were included in the ITT Population. 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Units	Counts
Participants

Secondary

12-week Change in Bloating

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

643 randomized patients received at least 1 dose of study drug. 642 patients were included in the ITT Population. 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Units	Counts
Participants

Secondary

12-week Change in 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".

643 randomized patients received at least 1 dose of study drug; 642 patients were included in the ITT Population; 10 patients who dropped out prior to finishing 1 week of the trial have missing data. 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	Linaclotide, 145μg	Linaclotide, 145μg dose, oral administration, once per day
OG001	Linaclotide, 290μg	Linaclotide, 290μg dose, oral administration, once per day
OG002	Placebo	Dose matched placebo, oral administration, once per day

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Linaclotide 145μg	Linaclotide, 145μg dose, oral administration, once per day	3	217	27	217
EG001	Linaclotide 290μg	Linaclotide, 290μg dose, oral administration, once per day	4	217	30	217
EG002	Placebo	Dose matched placebo, oral administration, once per day	5	209	14	209
EG003	Placebo to Linaclotide 290μg Randomized Withdrawal (RW) Period	Dose-matched placebo, oral administration, once per day or Linaclotide 290μg, oral administration, once per day.	0	177	20	177
EG004	Linaclotide 145μg to Placebo RW Period	Linaclotide 145μg, oral administration, once per day to Dose-matched placebo, oral administration, once per day	2	95	1	95
EG005	Linaclotide 145μg to Linaclotide 145μg RW Period	Linaclotide 145μg, oral administration, once per day to Linaclotide 145μg, oral administration, once per day	0	90	2	90
EG006	Linaclotide 290μg to Placebo RW Period	Linaclotide 290μg, oral administration, once per day to Dose-matched placebo, oral administration, once per day	0	86	0	86
EG007	Linaclotide 290μg to Linaclotide 290μg RW Period	Linaclotide 290μg, oral administration, once per day to Linaclotide 290μg, oral administration, once per day	0	90	1	90

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastroenteritis viral	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0010 events0 affected217 at risk EG0021 events1 affected209 at risk EG0030 events0 affected177 at risk EG0040 events0 affected95 at risk EG0050 events0 affected90 at risk EG0060 events0 affected86 at risk EG0070 events0 affected90 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected217 at risk EG0022 events2 affected209 at risk EG003
Pneumonia	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected217 at risk EG0021 events1 affected209 at risk EG003
Parathyroid tumor benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0010 events0 affected217 at risk EG0021 events1 affected209 at risk EG003
Bronchitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0010 events0 affected217 at risk EG0021 events1 affected209 at risk EG003
Chest pain	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected217 at risk EG0020 events0 affected209 at risk EG003
Cellulitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected217 at risk EG0020 events0 affected209 at risk EG003
Ectopic pregnancy	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected217 at risk EG0020 events0 affected209 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected217 at risk EG0020 events0 affected209 at risk EG003
Diverticulum intestinal hemorrhagic	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected217 at risk EG0020 events0 affected209 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected217 at risk EG0010 events0 affected217 at risk EG0020 events0 affected209 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment		EG00027 affected217 at risk EG00130 affected217 at risk EG00214 affected209 at risk EG00320 affected177 at risk EG0041 affected95 at risk EG0052 affected90 at risk EG0060 affected86 at risk EG0071 affected90 at risk