Diarrhea-predominant Irritable Bowel Syndrome
Conditions
Brief summary
Irritable bowel syndrome is a complex condition with a high unmet medical need for effective and safe treatment options. Lacteol® is a lactobacillus product used for adjunctive and symptomatic treatment of diarrhea. In this study, Lacteol® 340 mg will be evaluated as a potential therapy for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D).
Detailed description
This study will include the following phases: Screening Phase, Run-In Phase, Double-Blind Treatment Phase and Open-Label Treatment Phase. Screening: Eligibility of subjects will be evaluated following informed consent signature. Screening procedures/evaluations (physical exam, concomitant medications, clinical laboratory tests) and confirmation of eligibility following Rome III Diagnostic questionnaire will be performed. Run-In: Subjects will enter a 2-week Run-In Phase during which IBS Symptoms and Stool Characteristics will be recorded. At the end of the Run-In Phase, data collected over the last week will be reviewed. Upon confirmation of IBS-D severity status, subjects may be randomized. Double-Blind Treatment: Subjects will take study medication (either LACTEOL® 340 mg or Placebo) for 28 days. During this time, IBS Symptoms and Stool Characteristics and global assessment of relief will be recorded, and clinical laboratory tests will be performed. HAD score will be assessed at the end of the double blind treatment. Open-Label Treatment: All study completers will be eligible for a second 28 day Open-Label Treatment in the event that IBS-D symptoms remain or recur within the month following the end of Double-Blind Treatment. Subjects will take the study medication (LACTEOL® 340 mg) for 28 days. During this time, IBS Symptoms and Stool Characteristics and global assessment of relief will be recorded, and clinical laboratory tests will be performed.
Interventions
DRUGLACTEOL® 340 mg
LACTEOL® 340 mg will be taken for a 4-week duration (28 days) as three capsules a day: two capsules in the morning and one capsule in the evening.
DRUGPLACEBO
Matched LACTEOL® 340 mg Placebo will be taken for a 4-week duration (28 days) as three capsules a day: two capsules in the morning and one capsule in the evening.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* IBS-D diagnosis using the Rome III questionnaire * IBS Symptoms Severity Scale (IBS-SSS) score ranging between 100 and 400 * Bristol Stool Form Scale score exceeding two (\> 2) but less than seven (\< 7) * Stable diet * Mental and legal ability to sign informed consent
Exclusion criteria
* Diagnosis of Inflammatory Bowel Disease (IBD) * Chronic use of systemic steroids * Diagnosis of autoimmune Diseases or Disorders * Invasive abdominal surgery * Use of antibiotics prior to screening * Allergy to active substance or any other ingredient in LACTEOL® 340 mg * Congenital galactosemia, glucose, fructose and/or galactose malabsorption syndrome, lactase deficiency or lactose intolerance * Diagnosis of exocrine pancreatic insufficiency * Use of any experimental drug within the 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA) | Weekly Assessment (every 7 days) | Subjects were considered as responders if they had answered Yes to the following question at least 50% of the time during the 4-week treatment phase: Over the past week, do you consider that you have had satisfactory relief from your IBS symptoms? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | Weekly assessment (every 7 days) | The IBS-SSS has five questions related to four domains: abdominal pain severity and duration, abdominal distension, dissatisfaction with bowel habit and quality of life. The IBS-SSS score ranges from 0 (best outcome) to 500 (worst outcome). |
| Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Daily assessment | The Bristol Stool Form Scale score ranges from 1 to 7 from hard (score of 1) to watery (score of 7). Data are presented as the mean of daily assessments over a week. |
| Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase | At Screening and End of Double-Blind Treatment Phase | The HADS has 14 questions related to 2 domains: Anxiety subscale (7 questions) and Depression subscale (7 questions). Each question is graded from 0 (best outcome) to 3 (worst outcome), for a total score ranging from 0 (best outcome) to 42 (worst outcome). |
| Global Assessment of Relief During the Open-Label Treatment Phase Using the Subject Global Assessment (SGA) | Weekly Assessment (every 7 days) | Subjects were considered as responders if they had answered Yes to the following question at least 50% of the time during the 4-week treatment phase: Over the past week, do you consider that you have had satisfactory relief from your IBS symptoms? |
| Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | Daily assessment | The Bristol Stool Form Scale (BSFS) score ranges from 1 to 7 from hard (score of 1) to watery (score of 7). Data are presented as the mean of daily assessments over a week. |
| Use of Rescue Medication During the Double-Blind and Open-Label Treatment Phases of the Study | 8 weeks | Number of subjects using rescue medication (bisacodyl or loperamide) during each treatment phase of the study |
| Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | Weekly assessment (every 7 days) | The IBS-SSS has five questions related to four domains: abdominal pain severity and duration, abdominal distension, dissatisfaction with bowel habit and quality of life. The IBS-SSS score ranges from 0 (best outcome) to 500 (worst outcome). |
Countries
France, Germany
Participant flow
Recruitment details
First subject in: 22 June 2010; last subject out: 12 September 2011; ten (10) sites were recruited to participate in this trial and 7 of these (4 in France and 3 in Germany) enrolled subjects.
Pre-assignment details
Inclusion criteria related to symptom severity and stool characteristics assessed during 2nd week of Run-In Phase; ≥ 5 days of symptom data necessary for randomization; Double-Blind Phase completers eligible for a 28-day open-label treatment with LACTEOL® if symptoms not improved or recurring within 1 month after end of blinded treatment.
Participants by arm
| Arm | Count |
|---|---|
| LACTEOL® 340 mg LACTEOL® active medication was taken for a 4-week duration (28 days) as three capsules a day: two capsules in the morning and one capsule in the evening. | 13 |
| PLACEBO Matched LACTEOL® placebo was taken for a 4-week duration (28 days) as three capsules a day: two capsules in the morning and one capsule in the evening. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Phase | Lost to Follow-up | 2 | 0 |
| Double-Blind Treatment Phase | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | LACTEOL® 340 mg | PLACEBO | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 21 Participants |
| Region of Enrollment France | 6 participants | 6 participants | 12 participants |
| Region of Enrollment Germany | 7 participants | 7 participants | 14 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 2 / 13 | 2 / 17 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 17 |
Outcome results
Primary
Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA)
Subjects were considered as responders if they had answered Yes to the following question at least 50% of the time during the 4-week treatment phase: Over the past week, do you consider that you have had satisfactory relief from your IBS symptoms?
Time frame: Weekly Assessment (every 7 days)
Population: Analysis conducted on the Intent-to-Treat population defined as all randomized subjects; observed case (OC) data with no imputation made
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LACTEOL® 340 mg | Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA) | Responders | 30.8 percentage of participants |
| LACTEOL® 340 mg | Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA) | Non-responders | 69.2 percentage of participants |
| PLACEBO | Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA) | Responders | 30.8 percentage of participants |
| PLACEBO | Global Assessment of Relief During the Double-Blind Treatment Phase Using the Subject Global Assessment (SGA) | Non-responders | 69.2 percentage of participants |
Secondary
Global Assessment of Relief During the Open-Label Treatment Phase Using the Subject Global Assessment (SGA)
Subjects were considered as responders if they had answered Yes to the following question at least 50% of the time during the 4-week treatment phase: Over the past week, do you consider that you have had satisfactory relief from your IBS symptoms?
Time frame: Weekly Assessment (every 7 days)
Population: Analysis conducted on the Intent-to-Treat population defined as all subjects randomized to double-blind treatment and who subsequently entered the Open-Label Treatment Phase; observed case (OC) data with no imputation made; SGA data not available for one patient so that the analysis was performed on 16 rather than 17 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LACTEOL® 340 mg | Global Assessment of Relief During the Open-Label Treatment Phase Using the Subject Global Assessment (SGA) | Responders | 50.0 percentage of participants |
| LACTEOL® 340 mg | Global Assessment of Relief During the Open-Label Treatment Phase Using the Subject Global Assessment (SGA) | Non-responders | 50.0 percentage of participants |
Secondary
Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase
The HADS has 14 questions related to 2 domains: Anxiety subscale (7 questions) and Depression subscale (7 questions). Each question is graded from 0 (best outcome) to 3 (worst outcome), for a total score ranging from 0 (best outcome) to 42 (worst outcome).
Time frame: At Screening and End of Double-Blind Treatment Phase
Population: Analysis conducted on the Intent-to-Treat population defined as all randomized subjects; observed case (OC) data with no imputation made
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LACTEOL® 340 mg | Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase | Baseline HADS Total Score | 9.7 units on a scale (from 0 to 42) | Standard Deviation 5.14 |
| LACTEOL® 340 mg | Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase | HADS Total Score at End of Double-Blind Treatment | 9.9 units on a scale (from 0 to 42) | Standard Deviation 6.1 |
| PLACEBO | Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase | Baseline HADS Total Score | 10.7 units on a scale (from 0 to 42) | Standard Deviation 4.82 |
| PLACEBO | Hospital Anxiety and Depression Scale (HADS) Score During the Double-Blind Phase | HADS Total Score at End of Double-Blind Treatment | 9.5 units on a scale (from 0 to 42) | Standard Deviation 5.88 |
Secondary
Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale
The Bristol Stool Form Scale score ranges from 1 to 7 from hard (score of 1) to watery (score of 7). Data are presented as the mean of daily assessments over a week.
Time frame: Daily assessment
Population: Analysis conducted on the Intent-to-Treat population defined as all randomized subjects; observed case (OC) data with no imputation made. Number of participants analyzed refers to number of participants at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LACTEOL® 340 mg | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 1 | 4.3 units on a scale (from 1 ato 7) | Standard Deviation 1.29 |
| LACTEOL® 340 mg | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 3 | 4.4 units on a scale (from 1 ato 7) | Standard Deviation 1.52 |
| LACTEOL® 340 mg | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 2 | 4.6 units on a scale (from 1 ato 7) | Standard Deviation 1.33 |
| LACTEOL® 340 mg | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 4 | 4.4 units on a scale (from 1 ato 7) | Standard Deviation 1.32 |
| LACTEOL® 340 mg | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Baseline Bristol Stool Form Scale Score | 4.8 units on a scale (from 1 ato 7) | Standard Deviation 1.14 |
| PLACEBO | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 4 | 4.8 units on a scale (from 1 ato 7) | Standard Deviation 0.81 |
| PLACEBO | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Baseline Bristol Stool Form Scale Score | 4.9 units on a scale (from 1 ato 7) | Standard Deviation 0.64 |
| PLACEBO | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 1 | 4.8 units on a scale (from 1 ato 7) | Standard Deviation 0.61 |
| PLACEBO | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 2 | 4.8 units on a scale (from 1 ato 7) | Standard Deviation 0.83 |
| PLACEBO | Stool Characteristics During the Double-Blind Treatment Phase Using the Bristol Stool Form Scale | Bristol Stool Form Score during Week 3 | 4.4 units on a scale (from 1 ato 7) | Standard Deviation 0.78 |
Secondary
Stool Characteristics During the Open-Label Treatment Phase Using the BSFS
The Bristol Stool Form Scale (BSFS) score ranges from 1 to 7 from hard (score of 1) to watery (score of 7). Data are presented as the mean of daily assessments over a week.
Time frame: Daily assessment
Population: Analysis conducted on the Intent-to-Treat population defined as all subjects randomized to double-blind treatment and who subsequently entered the Open-Label Treatment Phase ; observed case (OC) data with no imputation made; baseline defined as the last non-missing assessment prior to the first dose of double-blind study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LACTEOL® 340 mg | Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | Double-Blind Baseline BSFS Score | 5.0 units on a scale (from 1 to 7) | Standard Deviation 0.68 |
| LACTEOL® 340 mg | Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | BSFS score during Week 1 | 4.6 units on a scale (from 1 to 7) | Standard Deviation 1.1 |
| LACTEOL® 340 mg | Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | BSFS score during Week 2 | 4.5 units on a scale (from 1 to 7) | Standard Deviation 1.24 |
| LACTEOL® 340 mg | Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | BSFS score during Week 3 | 4.4 units on a scale (from 1 to 7) | Standard Deviation 1.45 |
| LACTEOL® 340 mg | Stool Characteristics During the Open-Label Treatment Phase Using the BSFS | BSFS score during Week 4 | 4.4 units on a scale (from 1 to 7) | Standard Deviation 1.33 |
Secondary
Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score
The IBS-SSS has five questions related to four domains: abdominal pain severity and duration, abdominal distension, dissatisfaction with bowel habit and quality of life. The IBS-SSS score ranges from 0 (best outcome) to 500 (worst outcome).
Time frame: Weekly assessment (every 7 days)
Population: Analysis conducted on the Intent-to-Treat population defined as all randomized subjects; observed case (OC) data with no imputation made. Number of participants analyzed refers to number of participants at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LACTEOL® 340 mg | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 1 (Day 7) | 219.2 units on a scale (from 0 to 500) | Standard Deviation 76.36 |
| LACTEOL® 340 mg | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 3 (Day 21) | 233.6 units on a scale (from 0 to 500) | Standard Deviation 87.78 |
| LACTEOL® 340 mg | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 2 (Day 14) | 229.5 units on a scale (from 0 to 500) | Standard Deviation 81.95 |
| LACTEOL® 340 mg | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 4 (Day 28) | 228.6 units on a scale (from 0 to 500) | Standard Deviation 91.82 |
| LACTEOL® 340 mg | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | Baseline IBS-SSS score | 245.0 units on a scale (from 0 to 500) | Standard Deviation 87.3 |
| PLACEBO | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 4 (Day 28) | 241.4 units on a scale (from 0 to 500) | Standard Deviation 99.23 |
| PLACEBO | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | Baseline IBS-SSS score | 307.5 units on a scale (from 0 to 500) | Standard Deviation 72.36 |
| PLACEBO | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 1 (Day 7) | 271.2 units on a scale (from 0 to 500) | Standard Deviation 109.72 |
| PLACEBO | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 2 (Day 14) | 265.4 units on a scale (from 0 to 500) | Standard Deviation 99.93 |
| PLACEBO | Symptom Severity During the Double-Blind Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 3 (Day 21) | 254.8 units on a scale (from 0 to 500) | Standard Deviation 103.75 |
Secondary
Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score
The IBS-SSS has five questions related to four domains: abdominal pain severity and duration, abdominal distension, dissatisfaction with bowel habit and quality of life. The IBS-SSS score ranges from 0 (best outcome) to 500 (worst outcome).
Time frame: Weekly assessment (every 7 days)
Population: Analysis conducted on the Intent-to-Treat population defined as all subjects randomized to double-blind treatment and who subsequently entered the Open-Label Treatment Phase; observed case (OC) data with no imputation made; baseline defined as the last non-missing assessment prior to the first dose of double-blind medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LACTEOL® 340 mg | Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | Double-Blind Baseline IBS-SSS score | 270.5 units on a scale (from 0 to 500) | Standard Deviation 78.2 |
| LACTEOL® 340 mg | Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 1 (Day 7) | 224.6 units on a scale (from 0 to 500) | Standard Deviation 73.06 |
| LACTEOL® 340 mg | Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 2 (Day 14) | 211.5 units on a scale (from 0 to 500) | Standard Deviation 93.58 |
| LACTEOL® 340 mg | Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 3 (Day 21) | 199.2 units on a scale (from 0 to 500) | Standard Deviation 103.68 |
| LACTEOL® 340 mg | Symptom Severity During the Open-Label Treatment Phase Using the IBS Symptom Severity Scale (IBS-SSS) Total Score | IBS-SSS score at end of Week 4 (Day 28) | 222.5 units on a scale (from 0 to 500) | Standard Deviation 103.14 |
Secondary
Use of Rescue Medication During the Double-Blind and Open-Label Treatment Phases of the Study
Number of subjects using rescue medication (bisacodyl or loperamide) during each treatment phase of the study
Time frame: 8 weeks
Population: Analysis conducted on the Intent-to-Treat population for both treatment phases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LACTEOL® 340 mg | Use of Rescue Medication During the Double-Blind and Open-Label Treatment Phases of the Study | 2 participants |
| PLACEBO | Use of Rescue Medication During the Double-Blind and Open-Label Treatment Phases of the Study | 0 participants |
| LACTEOL® 340 mg Open-Label Period | Use of Rescue Medication During the Double-Blind and Open-Label Treatment Phases of the Study | 0 participants |