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Completed

NCT Number: NCT01642914

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

The purpose of this study is to evaluate the efficacy and safety of linaclotide compared with placebo in patients with chronic constipation (CC) and prominent abdominal bloating. This study includes an up to 3-week screening period and a 2-3 week pretreatment period. Patients who are eligible will be randomized to one of two doses of linaclotide or placebo for 12 weeks. This 12-week study will assess the effects of linaclotide on bowel movement frequency, as well as other abdominal and bowel symptoms of CC.

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Key information

Conditions

Chronic Constipation Constipation Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Forest Investigative Site 054, Greater Sudbury, Ontario, Canada

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient has completed a colonoscopy according to the American Gastroenterological Association criteria with no clinically significant findings
  • Patient has successfully completed protocol procedures (with no clinically significant findings)
  • Patient meets protocol criteria for Chronic Constipation(CC): < 3 bowel movements per week and reports one or more of the following symptoms for at least 12 weeks:
  • Straining during more than 25% of BMs
  • Lumpy or hard stools during more than 25% of BMs
  • Sensation of incomplete evacuation during more than 25% of BMs
  • Patient demonstrates continued chronic constipation and bloating through Pretreatment Period
  • Patient is compliant with Interactive voice response System (IVRS)

Exclusion criteria

  • Patient has a history of loose or watery stools
  • Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS)
  • Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
  • Patient has any protocol-excluded or clinically significant medical or surgical history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

Treatment and study plan

Linaclotide 290 micrograms

Drug

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

Linaclotide 145 micrograms

Drug

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

Matching Placebo

Drug

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

Primary outcomes

  1. 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder

    Time frame: 12-week treatment period

    A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.

Secondary outcomes

  1. 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder

    Time frame: 12-week treatment period

    A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.

  2. Change From Baseline in 12-Week Abdominal Bloating

    Time frame: Baseline and 12-week treatment period

    Abdominal Bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization (Visit 3, Day 1). The change from baseline in 12-Week Abdominal Bloating score is the difference between the average nonmissing daily patient assessments of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during the 12 week Treatment Period.

  3. Percent Change From Baseline in 12-week Abdominal Bloating

    Time frame: Baseline and 12-week treatment period

    Abdominal Bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). The percent change from baseline in 12-Week Abdominal Bloating score is the percentage difference between the average nonmissing daily patient assessments score of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during the 12 week Treatment Period.

  4. Percent Change From Baseline in Abdominal Bloating at Week 12

    Time frame: Baseline and Week 12

    Abdominal bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). The percent change from baseline at Week 12 in Abdominal Bloating score is the percentage difference between the average nonmissing daily patient assessments of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during Week 12.

  5. 6/12 Week Abdominal Bloating 30% Responder

    Time frame: 12-week treatment period

    A patient was a 6/12 week abdominal bloating 30% responder if, for at least 6 weeks of the 12-week treatment period, that patient's improvement from baseline in the weekly abdominal bloating score was ≥ 30% from baseline.

  6. Change From Baseline in 12-week CSBM Frequency Rate

    Time frame: Baseline and 12-week treatment period

    A patient's 12-week CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's 12-week CSBM frequency rate was the CSBM rate (CSBMs/week) calculated over the 12 weeks of the treatment period.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  7. Change From Baseline in CSBM Frequency Rate at Week 1.

    Time frame: Baseline and Week 1

    A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 1 was the CSBM rate (CSBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  8. Change From Baseline in CSBM Frequency Rate at Week 4.

    Time frame: Baseline and Week 4

    A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 4 was the CSBM rate (CSBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  9. Change From Baseline in CSBM Frequency Rate at Week 8

    Time frame: Baseline and Week 8

    A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 8 was the CSBM rate (CSBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  10. Change From Baseline in CSBM Frequency Rate at Week 12

    Time frame: Baseline and Week 12

    A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 12 was the CSBM rate (CSBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  11. Change From Baseline in 12-Week SBM Frequency Rate

    Time frame: 12-week treatment period

    A patient's Baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's 12-week SBM frequency rate was the SBM rate (SBMs/week) calculated over the 12 weeks of the treatment period.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  12. Change From Baseline in SBM Frequency Rate at Week 1

    Time frame: Baseline and Week 1

    A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at week 1 was the SBM rate (SBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  13. Change From Baseline in SBM Frequency Rate at Week 4

    Time frame: Baseline and Week 4

    A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at Week 4 was the SBM rate (SBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  14. Change From Baseline in SBM Frequency Rate at Week 8

    Time frame: Baseline and Week 8

    A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at Week 8 was the SBM rate (SBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  15. Change From Baseline in SBM Frequency Rate at Week 12

    Time frame: Baseline and Week 12

    A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at week 12 was the SBM rate (SBMs/week) calculated over that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  16. Change From Baseline in the Number of Days With a Spontaneous Bowel Movement (SBM)

    Time frame: Baseline and 12-week treatment period

    A patient's baseline number of days with a Spontaneous Bowel Movement (SBM) was calculated as the number of days with at least 1 Spontaneous Bowel Movement (SBM), derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's number of days with a SBM during the Treatment Period was calculated as the number of days with at least 1 Spontaneous Bowel Movement (SBM), divided by treatment duration (in days), and multiplied by 7.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  17. SBM Within 24 Hours After the First Dose of Investigational Product

    Time frame: 24 hours from first dose of investigational product (Day 1)

    The proportion of patients with a SBM within 24 hours of first taking investigational product in each linaclotide dose group was compared with the proportion in the placebo group using the Cochran-Mantel-Haenszel (CMH) test controlling for geographic region.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  18. Time to Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product

    Time frame: 12-week treatment period

    Time to first SBM after the first dose of investigation product was defined as the number of hours between the time of the first dose of investigational product to the occurrence of the first SBM. Patients who did not achieve an SBM were considered censored, with time to censoring defined as the number of hours elapsing from the time of the first dose of investigational product was taken to the end of the day of the last dose, at 12:00 AM (24:00 military time).

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  19. Change From Baseline in 12-week Stool Consistency

    Time frame: Baseline and 12-week treatment period

    Stool consistency was measured using the 7-point Bristol Stool Form Scale (BSFS):

    • = 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 patient's BSFS score for the baseline period (14 days before randomization, up to the time of randomization) and for the 12-week treatment period, was the average of the nonmissing BSFS scores from the SBMs reported by the patient during the respective baseline and treatment periods.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  20. Change From Baseline in Stool Consistency at Week 12

    Time frame: Baseline and Week 12

    Stool consistency was measured using the 7-point Bristol Stool Form Scale (BSFS):

    • = 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 patient's BSFS score for the baseline period (14 days before randomization, up to the time of randomization) and at week 12, was the average of the nonmissing BSFS scores from the SBMs reported by the patient during the respective baseline period and during Week 12.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  21. Change From Baseline in 12-week Severity of Straining

    Time frame: Baseline and 12-week treatment period

    Severity of straining was measured using a 5-point ordinal scale, where of value of 1 is "not at all" and a value of 5 is "an extreme amount." A patient's straining score for baseline was derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's straining score for the treatment period was the average of the nonmissing straining scores from the SBMs reported by the patient during the 12-week treatment period.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  22. Change From Baseline in Severity of Straining at Week 12

    Time frame: Baseline and Week 12

    Severity of straining was measured using a 5-point ordinal scale, where of value of 1 is "not at all" and a value of 5 is "an extreme amount."

    A patient's straining score for baseline was derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's straining score at Week 12 was the average of the nonmissing straining scores from the SBMs reported by that patient during analysis Week 12.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

  23. 9/12 Week Mild Straining and Diarrhea-free Responder

    Time frame: 12-week treatment period

    A patient was a 9/12 week mild straining and diarrhea-free responder if that patient met the weekly criterion for at least 9 weeks of the 12-week treatment period. A patient was considered to have met the weekly criterion in a given week if that patient had a nonmissing average straining score ≤ 2 (where a value of 1 represents no straining, an a value of 5 represents an extreme amount of straining), and the patient had no diarrhea adverse event (AE) reported for that week.

    Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

Sponsors and collaborators

Lead sponsor

Forest Laboratories

Industry

Collaborators

  • Ironwood Pharmaceuticals, Inc.

Registry information

Official study title

Phase 3b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Chronic Constipation and Prominent Abdominal Bloating at Baseline

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Jul 17, 2012
Registry last updated
Apr 26, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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