Chronic Intestinal Pseudo-obstruction
Conditions
Keywords
Rifaximin, L-105, phase 2 trial, CIPO, small intestinal bacterial overgrowth, systemic scleroderma
Brief summary
The objective of the study is to investigate efficacy and safety of rifaximin (L-105) in patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma
Detailed description
This is a placebo-controlled, randomized, double-blind, parallel group, comparative study, when patients with chronic idiopathic intestinal pseudo-obstruction(CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to the onset of systemic scleroderma, are administered rifaximin at 400 mg 3 times daily for 4 weeks. In addition, the time course of symptoms of the patients are to be confirmed for 8 weeks after the end of administration.
Interventions
Patients with chronic idiopathic intestinal pseudo-obstruction (CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma, are administered investigational product (rifaximin) for 4 weeks
DRUGPlacebo oral tablet
Patients with chronic idiopathic intestinal pseudo-obstruction (CIIPO) or patients with chronic intestinal pseudo-obstruction (CIPO), secondary to systemic scleroderma, are administered placebo for 4 weeks
Sponsors
ASKA Pharmaceutical Co., Ltd.
Yokohama City University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Outpatients aged ≥20 and \<75 on the day of informed consent (IC) * Patients with CIIPO (designated intractable disease 99) at enrollment, satisfying all the criteria specified in (1) to (7) of the CIIPO Diagnostic Criteria issued in 2014 by the MHLW Research Group, or patients with CIPO, secondary to systemic scleroderma, satisfying all the same criteria specified in (1) to (6) * Patients' levels of abdominal bloating symptoms, 4 scales of GSS, should be score 2 or 3 at the time of IC acquisition and enrollment.
Exclusion criteria
* Patients with malignant diseases (excluding those whose symptoms are stable and who do not require aggressive treatments such as chemotherapy and/or surgical therapy) * Patients with psychiatric diseases (excluding those whose symptoms are stable, and the investigator or coinvestigator concludes that efficacy of the patient can be assessed without any issue) * Patients with severe diabetes within 5 weeks before enrollment (HbA1c \>10%) * Patients who have already had gastrostomy (including percutaneousendoscopic gastro -jejunostomy, PEG-J), enterostomy, or colostomy * Patients who underwent intestinal decompression therapy not associated with surgical procedures (trans-nasal ileus tube) within 4weeks before enrollment * Patients who used antimicrobials, antiparasitics or antifungals (excluding topical use) within 4 weeks before enrollment * Patients who have changed the doses of the following concomitantly administered drugs within 4 weeks before enrollment: mosapride, daikenchuto, metoclopramide, acotiamide * Patients with severe hepatic disorders within 5 weeks before enrollment (who meet either one of the following criteria: AST≥ 5 x the upper limit of the common reference value specified in the Japanese Committee for Clinical Laboratory Standards (JCCLS), ALT≥ 5 x the upper limit of the common reference value specified in JCCLS, total bilirubin ≥ 3 x the upper limit of the common reference value specified in JCCLS, decompensated hematic cirrhosis, or jaundice) * Patients who are pregnant, breastfeeding, possibly pregnant, or those who wish to become pregnant * Patients with a previous history of hypersensitivity to any investigational product ingredients * Patients with active tuberculosis * Patients who participated in other clinical trial (including a trial with an investigational product) within 12 weeks before this enrollment and who received an intervention with a test drug * Other patients whose participation in the trial is concluded to be inappropriate by the investigator or coinvestigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement ratio (%) in abdominal bloating score in Global Symptomatic Score (GSS) | at the end of administration (4 weeks) | Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point Likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement. |
| Improvement ratio (%) in Gastrointestinal (GI) symptoms score | at the end of administration (4 weeks) | Gastrointestinal score (GI score) is a 5-point Likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms. Score 0 or 1 is defined as improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the good ratio (%) in gastrointestinal symptoms score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Gastrointestinal score (GI score), 5-point likert scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''. |
| Changes of total scores in Global Symptomatic Score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Sum of Global Symptomatic Score (GSS) of the following 7 symptoms, 0 to maximum of 21, are assessed; (a. diarrhea, b. epigastric pain/discomfort, c. abdominal distention, d. pain in the lower quadrant/discomfort, e. tenderness, f. nausea, g. vomiting). |
| Changes of the improvement ratio (%) in General health condition (symptoms) score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | General health condition (symptoms) score, a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement. |
| Changes of the good ratio (%) in General health condition (symptoms) score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | General health condition (symptoms) score, 5-point scale (0; very good, 1; good, 2; average, 3; bad, 4; extremely bad), with lower scores reflecting better conditions, is used. Score 0 or 1 is defined as ''good''. |
| Patient satisfaction score | At the end of the administration (4 weeks) | % of the satisfaction ratio in patient satisfaction score |
| Changes of Short Form (SF)-8 health survey score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | SF-8(short form-8), a self-reporting health survey ranging from 8 to maximum of 42, with lower scores reflecting better conditions, is used. |
| Small intestinal volume measured by abdominal CT scan | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Changes of small intestinal volume measured by abdominal CT scan |
| Changes from baseline of serum albumin level | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Serum albumin level is calculated for nutritional assessment |
| Changes from baseline of prealbumin (transthyretin) | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Prealbumin (transthyretin) is calculated for nutritional assessment |
| Changes from baseline of cholinesterase | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Cholinesterase is calculated for nutritional assessment |
| Changes from baseline of folic acid | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Folic acid is calculated for nutritional assessment |
| Changes from baseline of vitamin B12 (cobalamin) | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Vitamin B12 (cobalamin) is calculated for nutritional assessment |
| Changes from baseline of serum iron | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Serum iron is calculated for nutritional assessment |
| Changes of the improvement ratio (%) in gastrointestinal symptoms score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Gastrointestinal score (GI score), a 5-point likert scale (0; greatly improved, 1; improved, 2; no change, 3; worsened, 4; severely worsened), with lower scores reflecting more improved symptoms, is used. Score 0 or 1 is defined as improvement. |
| Changes of the improvement ratio (%) in abdominal bloating score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. Score 0 or 1 is defined as improvement. |
| Changes of abdominal bloating score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Abdominal bloating score in Global Symptomatic Score (GSS) is used. GSS is a 4-point likert scale ranging from 0 (no symptom) to 3 (severe, incapacitating with inability to perform normal activities), with lower scores reflecting better symptoms. |
| Changes of each score in Global Symptomatic Score other than abdominal bloating score | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Global Symptomatic Score (GSS), a 4-point likert scale ranging from 0 (no symptom) to 3 (severe), of the following symptoms are assessed; (a. diarrhea, b. epigastric pain/ discomfort, c. pain in the lower quadrant/discomfort, d. tenderness, e. nausea, f. vomiting). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | From the start of administration to 8 weeks after the end of administration | Incidence of adverse events |
| Changes from baseline of hematological parameters | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Hematological parameters (red blood cell count, hematocrit, white blood cell count, platelet count) are calculated for safety assessment |
| Changes from the baseline of total protein | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Total protein is calculated for safety assessment |
| Changes from the baseline of liver function | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Liver function parameters (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin) are calculated for safety assessment. |
| Changes from the baseline of renal function | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Creatinine and blood urea nitrogen are calculated for safety assessment. |
| Changes from the baseline of electrolytes | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Electrolytes (sodium, potassium, chlorine, calcium) are calculated for safety assessment. |
| Changes from the baseline of blood lipid level | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Blood lipid level (total cholesterol, triglyceride, and high-density lipoprotein cholesterol) is calculated for safety assessment. |
| Changes from the baseline of C reactive protein | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | C reactive protein is calculated for safety assessment. |
| Changes from the baseline of serum glucose level | Before, 2 and 4 weeks after administration; and 4 and 8 weeks after the end of administration | Serum glucose level is calculated for safety assessment. |
| Small intestinal bacterial overgrowth (SIBO) in a glucose-hydrogen breath test | Before, 4 weeks after administration;and 8 weeks after the end of administration | Elimination rate of SIBO in a glucose-hydrogen breath test |
| Changes of Serum endotoxin activity | Before, 2 and 4 weeks after administration;and 4 and 8 weeks after the end of administration | Serum endotoxin activity, ranging from 0.00-1.00, is assessed using EAA® (endotoxin activity assay, Toray Medical Co., Ltd.), FDA approved rapid whole blood assay for detection of human endotoxemia. 0.00-0.39 means low level, 0.40-0.59 means middle level, and ≥0.60 means high level. |
| Fecal test (intestinal flora) | Before and 4 weeks after administration | Changes of intestinal flora detected by 16SrDNA amplicon analysis using next generation sequencing. |
Countries
Japan
Outcome results
None listed