Effects of ROSE-010 on GI Transit in Constipation Predominant Irritable Bowel Syndrome (C-IBS) Patients
Condition: Irritable Bowel Syndrome Constipation Predominant
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): ROSE-010; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The study medication was used in 30 mcg, 100 mcg, and 300 mcg subcutaneous injections daily, depending upon study arm.; Placebo subcutaneous injection daily
Other intervention name(s): Glucagon-like peptide-1 (GLP-1) analogue; Glucagon-like peptide-1 (GLP-1) analogue
Intervention MeSH terms: Glucagon; Glucagon-Like Peptide 1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Constipation, Irritable Bowel Syndrome (IBS), Glucagon Like Peptide analogue