Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating

This study has been completed.
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT01642914
First received: July 13, 2012
Last updated: March 24, 2016
Last verified: March 2016
Results First Received: May 29, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Chronic Constipation
Constipation
Interventions: Drug: Linaclotide 290 micrograms
Drug: Linaclotide 145 micrograms
Drug: Matching placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patient recruitment occurred at 136 study sites in the US and 5 study sites in Canada over a 6 month period from August of 2012 to February of 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled participants had up to 21 days of screening (screening period) to determine eligibility for entry into the study's pretreatment period. After an additional 14 to 21 days of pretreatment, those patients meeting entry criteria were randomized for 12 weeks of double-blind treatment.

Reporting Groups
  Description
Placebo

Matching placebo

Matching placebo: oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 145 Micrograms

Linaclotide 145 micrograms

Linaclotide 145 micrograms: oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 290 Micrograms

Linaclotide 290 micrograms

Linaclotide 290 micrograms: oral capsule, taken once daily each morning at least 30 minutes before breakfast


Participant Flow:   Overall Study
    Placebo     Linaclotide 145 Micrograms     Linaclotide 290 Micrograms  
STARTED     173     154     160  
COMPLETED     127     122     120  
NOT COMPLETED     46     32     40  
Adverse Event                 11                 7                 15  
Lack of Efficacy                 9                 4                 2  
Protocol Violation                 15                 13                 6  
Withdrawal by Subject                 5                 5                 10  
Lost to Follow-up                 5                 3                 7  
Other Reason                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A total of 487 patients were randomized to treatment (Randomized Population). The Safety population consists of the 486 randomized who received at least one dose of study drug. The Demographic and Baseline Characteristics data reported here is for the Safety Population.

Reporting Groups
  Description
Placebo

Matching placebo

Matching placebo: oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 145 Micrograms

Linaclotide 145 micrograms

Linaclotide 145 micrograms: oral capsule, taken once daily each morning at least 30 minutes before breakfast

Linaclotide 290 Micrograms

Linaclotide 290 micrograms

Linaclotide 290 micrograms: oral capsule, taken once daily each morning at least 30 minutes before breakfast

Total Total of all reporting groups

Baseline Measures
    Placebo     Linaclotide 145 Micrograms     Linaclotide 290 Micrograms     Total  
Number of Participants  
[units: participants]
  173     153     160     486  
Age  
[units: Years]
Mean (Standard Deviation)
  46.3  (13.4)     48.3  (12.6)     47.5  (13.6)     47.3  (13.2)  
Age, Customized  
[units: participants]
       
Age 18 to 39 years     53     37     43     133  
Age 40 to 64 years     104     104     99     307  
Age ≥ 65 years     16     12     18     46  
Gender, Customized  
[units: participants]
       
Male     14     15     12     41  
Female     159     138     148     445  
Race/Ethnicity, Customized  
[units: participants]
       
White     120     97     112     329  
Black or African American     47     54     47     148  
American Indian or Alaska Native     0     0     1     1  
Asian     3     1     0     4  
Other     3     1     0     4  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic     26     19     25     70  
Non-Hispanic     147     134     135     416  
Region of Enrollment  
[units: participants]
       
United States     165     147     152     464  
Canada     8     6     8     22  
Weight, mean  
[units: kg]
Mean (Standard Deviation)
  77.59  (19.19)     79.39  (18.01)     80.53  (18.20)     79.12  (18.50)  
Height, mean  
[units: cm]
Mean (Standard Deviation)
  164.87  (8.65)     164.85  (8.44)     164.37  (7.07)     164.70  (8.08)  
BMI (Body Mass Index), mean  
[units: kilograms per meter squared]
Mean (Standard Deviation)
  28.43  (6.03)     29.17  (6.03)     29.83  (6.57)     29.12  (6.23)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder   [ Time Frame: 12-week treatment period ]

2.  Secondary:   9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder   [ Time Frame: 12-week treatment period ]

3.  Secondary:   Change From Baseline in 12-Week Abdominal Bloating   [ Time Frame: Baseline and 12-week treatment period ]

4.  Secondary:   Percent Change From Baseline in 12-week Abdominal Bloating   [ Time Frame: Baseline and 12-week treatment period ]

5.  Secondary:   Percent Change From Baseline in Abdominal Bloating at Week 12   [ Time Frame: Baseline and Week 12 ]

6.  Secondary:   6/12 Week Abdominal Bloating 30% Responder   [ Time Frame: 12-week treatment period ]

7.  Secondary:   Change From Baseline in 12-week CSBM Frequency Rate   [ Time Frame: Baseline and 12-week treatment period ]

8.  Secondary:   Change From Baseline in CSBM Frequency Rate at Week 1.   [ Time Frame: Baseline and Week 1 ]

9.  Secondary:   Change From Baseline in CSBM Frequency Rate at Week 4.   [ Time Frame: Baseline and Week 4 ]

10.  Secondary:   Change From Baseline in CSBM Frequency Rate at Week 8   [ Time Frame: Baseline and Week 8 ]

11.  Secondary:   Change From Baseline in CSBM Frequency Rate at Week 12   [ Time Frame: Baseline and Week 12 ]

12.  Secondary:   Change From Baseline in 12-Week SBM Frequency Rate   [ Time Frame: 12-week treatment period ]

13.  Secondary:   Change From Baseline in SBM Frequency Rate at Week 1   [ Time Frame: Baseline and Week 1 ]

14.  Secondary:   Change From Baseline in SBM Frequency Rate at Week 4   [ Time Frame: Baseline and Week 4 ]

15.  Secondary:   Change From Baseline in SBM Frequency Rate at Week 8   [ Time Frame: Baseline and Week 8 ]

16.  Secondary:   Change From Baseline in SBM Frequency Rate at Week 12   [ Time Frame: Baseline and Week 12 ]

17.  Secondary:   Change From Baseline in the Number of Days With a Spontaneous Bowel Movement (SBM)   [ Time Frame: Baseline and 12-week treatment period ]

18.  Secondary:   SBM Within 24 Hours After the First Dose of Investigational Product   [ Time Frame: 24 hours from first dose of investigational product (Day 1) ]

19.  Secondary:   Time to Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product   [ Time Frame: 12-week treatment period ]

20.  Secondary:   Change From Baseline in 12-week Stool Consistency   [ Time Frame: Baseline and 12-week treatment period ]

21.  Secondary:   Change From Baseline in Stool Consistency at Week 12   [ Time Frame: Baseline and Week 12 ]

22.  Secondary:   Change From Baseline in 12-week Severity of Straining   [ Time Frame: Baseline and 12-week treatment period ]

23.  Secondary:   Change From Baseline in Severity of Straining at Week 12   [ Time Frame: Baseline and Week 12 ]

24.  Secondary:   9/12 Week Mild Straining and Diarrhea-free Responder   [ Time Frame: 12-week treatment period ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Steven Shiff, Executive Director, Clinical Development
Organization: Forest Research Institute
phone: 201-427-8000 ext 8077
e-mail: Steven.Shiff@actavis.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01642914     History of Changes
Other Study ID Numbers: LIN-MD-04
Study First Received: July 13, 2012
Results First Received: May 29, 2014
Last Updated: March 24, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada