Irritable Bowel Syndrome Constipation Predominant Clinical Trial
Official title:
Effect of ROSE-010 on Gastrointestinal Motor Functions in Female Patients With Constipation Predominant Irritable Bowel Syndrome (C-IBS)
This trial will study the effects of an investigational (not FDA approved) medication,
ROSE-010, on the movement of food through the stomach, small intestine and colon in females
with constipation predominant irritable bowel syndrome (C-IBS).
The study hypothesis is that ROSE-010 will delay gastric emptying of solids and enhances
gastric accommodation without retarding colonic transit in female patients with C-IBS.
Methodology
Female patients with C-IBS will be screened for eligibility and informed about the study at
the initial screening visit Visit 1. Within two weeks of Visit 1, eligible patients will be
randomized to study medication, either 30 mcg, 100 mcg or 300 mcg ROSE-010 or placebo
administered via abdominal subcutaneous (s.c.) injection for a total of four days, three
consecutive days during transit scintigraphy and once prior to SPECT imaging. The allocation
to treatment group will be concealed.
Study medication will be administered at Visits 2, 3, and 4, the days of scintigraphic
assessment of gastric, small bowel and colonic transit of solids performed over a 48 hour
period.
Within two to seven days of Visit 4, patients will be instructed to return for
administration of a final injection of study medication followed by SPECT gastric
accommodation measurements (Visit 5). Within seven to ten days of Visit 5, patients will
return for Visit 6, final safety monitoring and an exit interview with study staff.
Investigational product, dosage and mode of administration
Patients will receive placebo or 30 mcg, 100 mcg or 300 mcg ROSE-010 administered s.c. in
the abdomen once on Visit 2, immediately before the standardized breakfast meal, fifteen
minutes before the first camera image is obtained. Study medication will be administered
fifteen minutes before camera images obtained on Visits 3 and 4. Study medication will be
administered immediately after the first fasting scan is obtained and before the second
fasting scan during SPECT at Visit 5.
Duration of treatment
ROSE-010 or matching placebo will be administered via abdominal s.c injection once daily for
three consecutive days and one final day two to seven days later, over a ten-day interval.
Duration of patients involvement in the study
Each patient will attend six visits at the clinic during a period of two to four weeks.
Efficacy assessments
1. Scintigraphic gastrointestinal and colonic transit
2. Technetium-99m (99mTc) SPECT measurement of gastric volumes
3. Assessment of stool frequency and consistency made by the patient using the Bowel
Pattern Diary
Safety assessments
The following safety assessments will be performed:
1. Laboratory safety tests, including a complete blood count (CBC), a comprehensive
metabolic panel (CMP), and urinalysis (UA) at Visit 1 (study entry) and Visit 6 (study
exit)
2. A physical examination by a study physician at Visit 1
3. Weight and vital signs (including temperature, pulse, blood pressure and respiration
rate) at every visit
4. Urine pregnancy tests performed at Visit 1 and within 48 hours prior to receipt of
radiation at Visit 2 transit test and Visit 5 SPECT test
5. Interview for concomitant medications and adverse events at every visit
Statistical methods
An analysis of covariance (ANCOVA) will be used to compare transit parameters and gastric
volumes among the treatment groups. If necessary a suitable transformation for potential
skewness in the distributions of measured volumes may be used (e.g., ANCOVA on ranks or log
volumes). If ANCOVA shows a p value less than or equal to 0.10, then both the 100 mcg and
300 mcg doses will be compared to placebo (p value less than or equal to 0.25). Dunnett's
Test will be used to compare each dose group with placebo. Since each of the primary
endpoints assesses a separate hypothesis regarding the effects of ROSE-010, no adjustment in
the alpha level for testing multiple types of endpoints is anticipated, and a two-sided
significance level of 0.05 will be used in each ANCOVA model.
Analysis data sets
The primary analyses will follow the intent to treat (ITT) paradigm with all patients
randomized included in the analyses. Those patients with missing response values will have
their missing values imputed via the overall (patients with non-missing data) mean and a
corresponding adjustment in the ANCOVA residual error variance degrees of freedom
(subtracting one for each missing value imputed). Safety data will be presented for all
patients receiving investigational product.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment