Clinical trial NCT00526097: Dulcolax vs Placebo in Functional Constipation
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Constipation
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-09-06
Enrollment: 368
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Mean Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week Over the 4 Weeks Treatment Period
timeFrame: 4 Weeks
Secondary outcomes:
measure: Number of CSBMs at Week 1
timeFrame: Week 1 in treatment period
measure: Number of CSBMs at Week 2
timeFrame: Week 2 in treatment period
measure: Number of CSBMs at Week 3
timeFrame: Week 3 in treatment period
measure: Number of CSBMs at Week 4
timeFrame: Week 4 in treatment period
measure: Mean Number of SBMs Per Week Over the 4 Weeks Treatment Period
timeFrame: 4 Weeks
measure: Number of SBMs at Week 1
timeFrame: Week 1 in treatment period
measure: Number of SBMs at Week 2
timeFrame: Week 2 in treatment period
measure: Number of SBMs at Week 3
timeFrame: Week 3 in treatment period
measure: Number of SBMs at Week 4
timeFrame: Week 4 in treatment period
measure: Time to the First SBM Following the First Dose of Study Medication (SM)
timeFrame: Time of first dose of SM up to 4 weeks
measure: 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
timeFrame: Baseline and 4 weeks
measure: Number of Participants With an Increase of at Least 1 CSBM at Week 1 Compared to Baseline
timeFrame: Baseline and week 1 in treatment period
measure: Number of Participants With an Increase of at Least 1 CSBM at Week 2 Compared to Baseline
timeFrame: Baseline and week 2 in treatment period
measure: Number of Participants With an Increase of at Least 1 CSBM at Week 3 Compared to Baseline
timeFrame: Baseline and week 3 in treatment period
measure: Number of Participants With an Increase of at Least 1 CSBM at Week 4 Compared to Baseline
timeFrame: Baseline and week 4 in treatment period
measure: Number of Participants With a Mean of at Least 1 CSBM a Day Over the 4 Weeks Treatment Period
timeFrame: 4 weeks
measure: Number of Participants With a Mean of at Least 3 CSBMs a Week Over the 4 Weeks Treatment Period
timeFrame: 4 weeks
measure: Number of Premature Withdrawals Over the 4 Weeks Treatment Period
timeFrame: 4 weeks
measure: Number of Premature Withdrawals at Week 1 in the Treatment Period
timeFrame: Week 1 in the treatment period
measure: Number of Premature Withdrawals at Week 2 in the Treatment Period
timeFrame: Week 2 in the treatment period
measure: Number of Premature Withdrawals at Week 3 in the Treatment Period
timeFrame: Week 3 in the treatment period
measure: Number of Premature Withdrawals at Week 4 in the Treatment Period
timeFrame: Week 4 in the treatment period
measure: Number of Participants Using Rescue Medication Over the 4 Weeks Treatment Period
timeFrame: 4 weeks
measure: Number of Participants Using Rescue Medication at Week 1 in the Treatment Period
timeFrame: Week 1 in the treatment period
measure: Number of Participants Using Rescue Medication at Week 2 in the Treatment Period
timeFrame: Week 2 in the treatment period
measure: Number of Participants Using Rescue Medication at Week 3 in the Treatment Period
timeFrame: Week 3 in the treatment period
measure: Number of Participants Using Rescue Medication at Week 4 in the Treatment Period
timeFrame: Week 4 in the treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 1
timeFrame: Baseline and week 1 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 2
timeFrame: Baseline and week 2 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 3
timeFrame: Baseline and week 3 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Straining' at Week 4
timeFrame: Baseline and week 4 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 1
timeFrame: Baseline and week 1 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 2
timeFrame: Baseline and week 2 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 3
timeFrame: Baseline and week 3 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Stool Quality' at Week 4
timeFrame: Baseline and week 4 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 1
timeFrame: Baseline and week 1 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 2
timeFrame: Baseline and week 2 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 3
timeFrame: Baseline and week 3 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Sensation of Incomplete Evacuation' at Week 4
timeFrame: Baseline and week 4 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 1
timeFrame: Baseline and week 1 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 2
timeFrame: Baseline and week 2 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 3
timeFrame: Baseline and week 3 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Anorectal Obstructions/Blockade' at Week 4
timeFrame: Baseline and week 4 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 1
timeFrame: Baseline and week 1 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 2
timeFrame: Baseline and week 2 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 3
timeFrame: Baseline and week 3 in treatment period
measure: Change From Baseline in the Mean Score for Constipation Symptom 'Manual Manoeuvre' at Week 4
timeFrame: Baseline and week 4 in treatment period
measure: Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 1 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 1 in the treatment period
measure: Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 2 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 2 in the treatment period
measure: Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 3 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 3 in the treatment period
measure: Number of Participants With Improved, Unchanged or Worsened Overall Satisfaction With Bowel Habits at Week 4 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 4 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 1 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 1 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 2 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 2 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 3 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 3 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Constipation at Week 4 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 4 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 1 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 1 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 2 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 2 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 3 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 3 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Bloating at Week 4 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 4 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 1 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 1 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 2 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 2 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 3 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 3 in the treatment period
measure: Number of Participants With Reduced, Unchanged or Increased Bothersomeness With Abdominal Discomfort at Week 4 in the Treatment Period in Comparison to Baseline
timeFrame: Baseline and week 4 in the treatment period
measure: Number of Participants With Respect to the Final Global Assessment of Efficacy by the Investigator
timeFrame: 4 weeks
measure: Number of Participants With Respect to the Final Global Assessment of Efficacy by the Patient
timeFrame: 4 weeks
measure: Number of Participants With Respect to the Final Global Assessment of Tolerability by the Investigator
timeFrame: 4 weeks
measure: Number of Participants With Respect to the Final Global Assessment of Tolerability by the Patient
timeFrame: 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Physical Functioning'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Role Limitation Due to Physical Problems'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Bodily Pain'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'General Health'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Vitality'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Social Functioning'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Role Limitation Due to Emotional Problems'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Dimension 'Mental Health'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Mental Component Scale (MCS)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the SF-36 Physical Component Scale (PCS)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the PAC-QoL Subscale 'Worries and Concerns'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the PAC-QoL Subscale 'Physical Discomfort'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the PAC-QoL Subscale 'Psychosocial Discomfort'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the PAC-QoL Subscale 'Satisfaction'
timeFrame: Baseline and 4 weeks
measure: Change From Baseline in the PAC-QoL Overall Score
timeFrame: Baseline and 4 weeks
measure: Change From Baseline for Sodium (Normalized Value)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline for Potassium (Normalized Value)
timeFrame: Baseline and 4 weeks
measure: Change From Baseline for Chloride (Normalized Value)
timeFrame: Baseline and 4 weeks
Other outcomes:
Locations:
city: Addlestone
country: United Kingdom
facility: 122.56.44032 Boehringer Ingelheim Investigational Site
city: Ash Vale, Aldershot
country: United Kingdom
facility: 122.56.44018 Boehringer Ingelheim Investigational Site
city: Ashford
country: United Kingdom
facility: 122.56.44029 Boehringer Ingelheim Investigational Site
city: Atherstone
country: United Kingdom
facility: 122.56.44023 Boehringer Ingelheim Investigational Site
city: Bedworth
country: United Kingdom
facility: 122.56.44011 Boehringer Ingelheim Investigational Site
city: Bennetthorpe, Doncaster
country: United Kingdom
facility: 122.56.44009 Boehringer Ingelheim Investigational Site
city: Bexhill on Sea
country: United Kingdom
facility: 122.56.44025 Boehringer Ingelheim Investigational Site
city: Blackpool
country: United Kingdom
facility: 122.56.44012 Boehringer Ingelheim Investigational Site
city: Burbage
country: United Kingdom
facility: 122.56.44024 Boehringer Ingelheim Investigational Site
city: Cardiff
country: United Kingdom
facility: 122.56.44003 Boehringer Ingelheim Investigational Site
city: Chesterfield
country: United Kingdom
facility: 122.56.44017 Boehringer Ingelheim Investigational Site
city: Chippenham
country: United Kingdom
facility: 122.56.44014 Boehringer Ingelheim Investigational Site
city: Chorley
country: United Kingdom
facility: 122.56.44006 Boehringer Ingelheim Investigational Site
city: Dundee
country: United Kingdom
facility: 122.56.44033 Boehringer Ingelheim Investigational Site
city: Edgbaston, Birmingham
country: United Kingdom
facility: 122.56.44002 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 122.56.44004 Boehringer Ingelheim Investigational Site
city: Leamington Spa
country: United Kingdom
facility: 122.56.44020 Boehringer Ingelheim Investigational Site
city: Liverpool
country: United Kingdom
facility: 122.56.44007 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 122.56.44005 Boehringer Ingelheim Investigational Site
city: Midsomer Norton
country: United Kingdom
facility: 122.56.44010 Boehringer Ingelheim Investigational Site
city: Newtonabbey
country: United Kingdom
facility: 122.56.44021 Boehringer Ingelheim Investigational Site
city: Paignton
country: United Kingdom
facility: 122.56.44022 Boehringer Ingelheim Investigational Site
city: Slough
country: United Kingdom
facility: 122.56.44001 Boehringer Ingelheim Investigational Site
city: Sunbury-on-Thames
country: United Kingdom
facility: 122.56.44026 Boehringer Ingelheim Investigational Site
city: Swindon
country: United Kingdom
facility: 122.56.44019 Boehringer Ingelheim Investigational Site
city: Warminster
country: United Kingdom
facility: 122.56.44015 Boehringer Ingelheim Investigational Site
city: Wolverhampton
country: United Kingdom
facility: 122.56.44008 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: