Dulcolax vs Placebo in Functional Constipation

A Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks Treatment With Bisacodyl (Dulcolax) Tablets 10mg Administered Orally, Once Daily, in Patients With Functional Constipation.

Sponsors

Lead Sponsor: Boehringer Ingelheim

Source Boehringer Ingelheim
Brief Summary

The objective of the study was to compare the efficacy and safety of 4 weeks treatment with bisacodyl (Dulcolax) tablets 10 mg to placebo in patients with functional constipation. In addition, the effect of treatment on quality of life and general health status was evaluated.

Overall Status Completed
Start Date September 2007
Primary Completion Date June 2009
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week Over the 4 Weeks Treatment Period 4 Weeks
Secondary Outcome
Measure Time Frame
Number of CSBMs at Week 1 Week 1 in treatment period
Number of CSBMs at Week 2 Week 2 in treatment period
Number of CSBMs at Week 3 Week 3 in treatment period
Number of CSBMs at Week 4 Week 4 in treatment period
Mean Number of SBMs Per Week Over the 4 Weeks Treatment Period 4 Weeks
Number of SBMs at Week 1 Week 1 in treatment period
Number of SBMs at Week 2 Week 2 in treatment period
Number of SBMs at Week 3 Week 3 in treatment period
Number of SBMs at Week 4 Week 4 in treatment period
Time to the First SBM Following the First Dose of Study Medication (SM) Time of first dose of SM up to 4 weeks
Number of Participants With an Increase of at Least 1 in the Mean Number of CSBMs Per Week Over the 4 Weeks Treatment Period Compared to Baseline Baseline and 4 weeks
Number of Participants With an Increase of at Least 1 CSBM at Week 1 Compared to Baseline Baseline and week 1 in treatment period
Number of Participants With an Increase of at Least 1 CSBM at Week 2 Compared to Baseline Baseline and week 2 in treatment period
Number of Participants With an Increase of at Least 1 CSBM at Week 3 Compared to Baseline Baseline and week 3 in treatment period
Number of Participants With an Increase of at Least 1 CSBM at Week 4 Compared to Baseline Baseline and week 4 in treatment period
Number of Participants With a Mean of at Least 1 CSBM a Day Over the 4 Weeks Treatment Period 4 weeks
Number of Participants With a Mean of at Least 3 CSBMs a Week Over the 4 Weeks Treatment Period 4 weeks
Number of Premature Withdrawals Over the 4 Weeks Treatment Period 4 weeks
Number of Premature Withdrawals at Week 1 in the Treatment Period Week 1 in the treatment period
Number of Premature Withdrawals at Week 2 in the Treatment Period Week 2 in the treatment period
Number of Premature Withdrawals at Week 3 in the Treatment Period Week 3 in the treatment period
Number of Premature Withdrawals at Week 4 in the Treatment Period Week 4 in the treatment period
Number of Participants Using Rescue Medication Over the 4 Weeks Treatment Period 4 weeks
Number of Participants Using Rescue Medication at Week 1 in the Treatment Period Week 1 in the treatment period
Number of Participants Using Rescue Medication at Week 2 in the Treatment Period Week 2 in the treatment period
Number of Participants Using Rescue Medication at Week 3 in the Treatment Period Week 3 in the treatment period
Number of Participants Using Rescue Medication at Week 4 in the Treatment Period Week 4 in the treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 1 Baseline and week 1 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 2 Baseline and week 2 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 3 Baseline and week 3 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 4 Baseline and week 4 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 1 Baseline and week 1 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 2 Baseline and week 2 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 3 Baseline and week 3 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 4 Baseline and week 4 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 1 Baseline and week 1 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 2 Baseline and week 2 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 3 Baseline and week 3 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 4 Baseline and week 4 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 1 Baseline and week 1 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 2 Baseline and week 2 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 3 Baseline and week 3 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 4 Baseline and week 4 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 1 Baseline and week 1 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 2 Baseline and week 2 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 3 Baseline and week 3 in treatment period
Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 4 Baseline and week 4 in treatment period
Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 1 in the Treatment Period in Comparison to Baseline Baseline and week 1 in the treatment period
Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 2 in the Treatment Period in Comparison to Baseline Baseline and week 2 in the treatment period
Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 3 in the Treatment Period in Comparison to Baseline Baseline and week 3 in the treatment period
Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 4 in the Treatment Period in Comparison to Baseline Baseline and week 4 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 1 in the Treatment Period in Comparison to Baseline Baseline and week 1 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 2 in the Treatment Period in Comparison to Baseline Baseline and week 2 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 3 in the Treatment Period in Comparison to Baseline Baseline and week 3 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 4 in the Treatment Period in Comparison to Baseline Baseline and week 4 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 1 in the Treatment Period in Comparison to Baseline Baseline and week 1 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 2 in the Treatment Period in Comparison to Baseline Baseline and week 2 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 3 in the Treatment Period in Comparison to Baseline Baseline and week 3 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 4 in the Treatment Period in Comparison to Baseline Baseline and week 4 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 1 in the Treatment Period in Comparison to Baseline Baseline and week 1 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 2 in the Treatment Period in Comparison to Baseline Baseline and week 2 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 3 in the Treatment Period in Comparison to Baseline Baseline and week 3 in the treatment period
Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 4 in the Treatment Period in Comparison to Baseline Baseline and week 4 in the treatment period
Number of Participants With Respect to the Final Global Assessment of Efficacy by the Investigator 4 weeks
Number of Participants With Respect to the Final Global Assessment of Efficacy by the Patient 4 weeks
Number of Participants With Respect to the Final Global Assessment of Tolerability by the Investigator 4 weeks
Number of Participants With Respect to the Final Global Assessment of Tolerability by the Patient 4 weeks
Change From Baseline in the SF-36 Dimension 'Physical Functioning' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Role Limitation Due to Physical Problems' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Bodily Pain' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'General Health' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Vitality' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Social Functioning' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Role Limitation Due to Emotional Problems' Baseline and 4 weeks
Change From Baseline in the SF-36 Dimension 'Mental Health' Baseline and 4 weeks
Change From Baseline in the SF-36 Mental Component Scale (MCS) Baseline and 4 weeks
Change From Baseline in the SF-36 Physical Component Scale (PCS) Baseline and 4 weeks
Change From Baseline in the PAC-QoL Subscale 'Worries and Concerns' Baseline and 4 weeks
Change From Baseline in the PAC-QoL Subscale 'Physical Discomfort' Baseline and 4 weeks
Change From Baseline in the PAC-QoL Subscale 'Psychosocial Discomfort' Baseline and 4 weeks
Change From Baseline in the PAC-QoL Subscale 'Satisfaction' Baseline and 4 weeks
Change From Baseline in the PAC-QoL Overall Score Baseline and 4 weeks
Change From Baseline for Sodium (Normalized Value) Baseline and 4 weeks
Change From Baseline for Potassium (Normalized Value) Baseline and 4 weeks
Change From Baseline for Chloride (Normalized Value) Baseline and 4 weeks
Enrollment 368
Condition
Intervention

Intervention Type: Drug

Intervention Name: Bisacodyl 10 mg

Description: 2 x 5 mg bisacodyl once daily

Arm Group Label: Bisacodyl 5 mg x 2 once daily

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo-to-match bisacodyl 10 mg (2 x 5 mg) once daily

Arm Group Label: Placebo

Eligibility

Criteria:

Inclusion Criteria:

1. Male and female patients, aged 18 and above

2. Suffering from functional constipation, according to their medical history, as defined by the Rome III diagnostic criteria , i.e.:Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

1. Must include 2 or more of the following::

- straining during at least 25% of the defecations

- lumpy or hard stools in at least 25% of the defecations

- sensation of incomplete evacuation for at least 25% of the defecations

- sensation of anorectal obstruction/blockade for at least 25% of the defecations

- manual manoeuvres to facilitate at least 25% of the defecations (e.g. digital evacuation, support of the pelvic floor)

- fewer than 3 defecations per week

2. Loose stools are rarely present without the use of laxatives

3. There are insufficient criteria for irritable bowel syndrome (IBS)

3. Able and willing to complete a daily e-diary

4. Able and willing to use the trial rescue medication

5. Signed and dated written informed consent prior to enrolment into the study in accordance with GCP and local legislation

At Visit 2, patients must comply with the following additional inclusion criteria to be eligible for entry into the treatment phase:

6. Functional constipation is confirmed by e-diary data at the end of the baseline period:

a. An average of less than 3 CSBMs per week, together with at least one of the following symptoms occurring at least 25% of the time:

- straining

- incomplete evacuation

- lumpy or hard stools (i.e. type 1 or type 2 stools)

7. Compliant with the use of the e-diary throughout the baseline period (compliance is defined as completing 80% of the evening reports)

8. Compliant with the use of rescue medication throughout the baseline period. Compliance is defined as follows:

- rescue medication may be used if there has not been a bowel movement for more than 72 hrs rescue medication may not be used on either day -1 or on the day of randomisation (day 1)

Exclusion Criteria:

1. Eating disorders such as anorexia nervosa and bulimia, as a cause of excessive use of laxatives

2. Patients whose constipation is caused by primary organic disease of the colon or pelvic floor

3. Patients with metabolic disorders, neurological disorders, severe or psychiatric disorders, or any other significant disease or intercurrent illness (e.g. abdominal/gastrointestinal surgery) that, in the Investigators opinion, would interfere with participation in the trial

4. Patients with restricted mobility (e.g. wheelchair bound, or bed-ridden) that, in the Investigators opinion, would interfere with participation in the trial

5. Patients with a known hypersensitivity to bisacodyl or any other ingredient in the study medication

6. Patients with ileus, intestinal obstruction, acute surgical abdominal conditions (such as acute appendicitis and acute inflammatory bowel diseases), or severe dehydration

7. Patients with anal fissures or ulcerative proctitis with mucosal damage

8. Patients with known clinically significant abnormal electrolyte values

9. Patients whose concomitant therapy includes an opioid medication (e.g. morphine, codeine)

10. Constipation which, in the Investigators opinion, is caused by medication (e.g. anticholinergics)

11. Patients who are not willing to discontinue the use of prohibited concomitant therapy

12. Pre-menopausal women who:

1. are nursing (breast-feeding) or who are pregnant OR

2. who are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study. Acceptable methods of birth control include:

- transdermal patch

- intra-uterine devices/systems (IUDs/IUSs)

- oral, implantable or injectable contraceptives

- sexual abstinence

- sterilisation or a vasectomised partner

13. Participation in another trial with an investigational product with 1 month of enrolment into this study

14. Drug or alcohol abuse

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Boehringer Ingelheim Study Chair Boehringer Ingelheim
Location
Facility:
122.56.44032 Boehringer Ingelheim Investigational Site | Addlestone, United Kingdom
122.56.44018 Boehringer Ingelheim Investigational Site | Ash Vale, Aldershot, United Kingdom
122.56.44029 Boehringer Ingelheim Investigational Site | Ashford, United Kingdom
122.56.44023 Boehringer Ingelheim Investigational Site | Atherstone, United Kingdom
122.56.44011 Boehringer Ingelheim Investigational Site | Bedworth, United Kingdom
122.56.44009 Boehringer Ingelheim Investigational Site | Bennetthorpe, Doncaster, United Kingdom
122.56.44025 Boehringer Ingelheim Investigational Site | Bexhill on Sea, United Kingdom
122.56.44012 Boehringer Ingelheim Investigational Site | Blackpool, United Kingdom
122.56.44024 Boehringer Ingelheim Investigational Site | Burbage, United Kingdom
122.56.44003 Boehringer Ingelheim Investigational Site | Cardiff, United Kingdom
122.56.44017 Boehringer Ingelheim Investigational Site | Chesterfield, United Kingdom
122.56.44014 Boehringer Ingelheim Investigational Site | Chippenham, United Kingdom
122.56.44006 Boehringer Ingelheim Investigational Site | Chorley, United Kingdom
122.56.44033 Boehringer Ingelheim Investigational Site | Dundee, United Kingdom
122.56.44002 Boehringer Ingelheim Investigational Site | Edgbaston, Birmingham, United Kingdom
122.56.44004 Boehringer Ingelheim Investigational Site | Glasgow, United Kingdom
122.56.44020 Boehringer Ingelheim Investigational Site | Leamington Spa, United Kingdom
122.56.44007 Boehringer Ingelheim Investigational Site | Liverpool, United Kingdom
122.56.44005 Boehringer Ingelheim Investigational Site | Manchester, United Kingdom
122.56.44010 Boehringer Ingelheim Investigational Site | Midsomer Norton, United Kingdom
122.56.44021 Boehringer Ingelheim Investigational Site | Newtonabbey, United Kingdom
122.56.44022 Boehringer Ingelheim Investigational Site | Paignton, United Kingdom
122.56.44001 Boehringer Ingelheim Investigational Site | Slough, United Kingdom
122.56.44026 Boehringer Ingelheim Investigational Site | Sunbury-on-Thames, United Kingdom
122.56.44019 Boehringer Ingelheim Investigational Site | Swindon, United Kingdom
122.56.44015 Boehringer Ingelheim Investigational Site | Warminster, United Kingdom
122.56.44008 Boehringer Ingelheim Investigational Site | Wolverhampton, United Kingdom
Location Countries

United Kingdom

Verification Date

December 2013

Responsible Party

Name Title: Boehringer Ingelheim, Study Chair

Organization: Boehringer Ingelheim

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Bisacodyl 5 mg x 2 once daily

Type: Experimental

Description: patient to receive two enteric-coated tablets containing 5 mg bisacodyl

Label: Placebo

Type: Placebo Comparator

Description: patient to receive two placebo-to-match enteric-coated tablets 5 mg bisacodyl

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double

Source: ClinicalTrials.gov