| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | diarrhea-predominant irritable bowel syndrome | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Classification code | 10023003 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To investigate the potential efficacy, safety and tolerability of different oral doses of YM060 in patients with diarrhea-predominant irritable bowel syndrome | |
| E.2.2 | Secondary objectives of the trial | To identify dose(s) for future phase III clinical studies
To obtain data on population pharmacokinetics
| |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | At study entry (visit 1):
1.Patient who signs written informed consent.
2.Male or female patient aged between 18-70 years.
3.a. Patient meets Rome II criteria for IBS(2) , i.e.: at least 3 weeks or more, which need not be consecutive, in the preceding 3 months of abdominal discomfort or pain that has two out of three following features:
(1) Relieved with defecation; and/or
(2) Onset associated with a change in frequency of stool; and/or
(3) Onset associated with a change in form (appearance) of stool
b. Patient is identified as having d-IBS, i.e.: one or more of question 2, 4 or 6 from the Questions and Rules to Identify d-IBS Patient (Appendix 5) are rated 2 or above, and questions 1, 3 and 5 are rated 0 or 1.
4.Patient in whom organic disease has been ruled out after being diagnosed with IBS, within 5 years prior to the run-in, by a sigmoidoscopic (for patients <50 yrs), colonoscopic (for patients ³50 yrs) or contrast-enema examination. Source documentation must be obtained as evidence. However, IBS patients with benign polyps or colonic diverticulosis which is judged to have no influence on the digestive tract passage are acceptable
5.Regarding stool form, the patient’s main complaint is diarrhea
At randomization (visit 2):
6.Patient who answered all daily questions for at least 5 days per week, and answered all the weekly questions during the 2-week run-in period
7.Patient whose average daily scores of abdominal discomfort or pain are greater than 0.7 based on a 5-point severity scale during the run-in period
Abdominal discomfort/pain severity score:
0: None, 1: mild, 2: moderate, 3: severe, 4: intolerable
| |
| E.4 | Principal exclusion criteria | Patient will be excluded from participation if any of the following apply:
At study entry (visit 1):
1.Patient with a history of surgical resection of the stomach, small intestine or large intestine (excluding resection of the appendix or benign polyps)
2.Patient with a history of inflammatory intestinal diseases (Crohn’s disease or ulcerative colitis)
3.Patient with a history of ischemic colitis
4.Patient with infectious enteritis
5.Patient with any disease, other than IBS, potentially affecting the digestive tract passage or colonic function
6.Patient requiring treatment with any of the non-permitted drugs which has not been safely stopped 3 days prior to the 2-week run-in period
7.Patient who has a history of drug or alcohol abuse within 1 year prior to the start of this clinical trial
8.Patient with malignant melanoma and any non-skin malignancy within 5 years prior to the start of this clinical trial
9.Patient with thyroid dysfunction
10.Patient receiving radiotherapy for abdominal disease
11.Patient with severe cardiovascular disease, respiratory diseases, renal diseases, hepatic diseases, digestive tract diseases (excluding IBS), blood diseases, or neurological or psychiatric diseases
12.Female of child-bearing potential without using a medically acceptable method of birth control (medically acceptable methods of birth control are: intra-uterine devices, vaginal device, contraceptive pills of combination type, contraceptive patch, barrier method, hormonal implants and injectable contraceptives, or female being surgically sterile or being at least 1-year postmenopausal)
13.Pregnant woman or lactating mother or woman with an intention of pregnancy
14.Participation in any clinical study within 3 months, or participation in more than 3 clinical studies within 12 months, prior to visit 1
15.Known allergy to the study drug, any of its components or any other 5-HT3 antagonists.
16.Any clinical condition which, in the opinion of the investigator would not allow safe completion of the study
17.Employee of the Yamanouchi Group or CRO involved in the study
At randomization (visit 2):
18.Patient reported having any Type 1 or Type 2 stool on the Bristol Stool Form Scale during the run-in period (see Appendix 6 for the detailed description and illustration of the Bristol Stool Form Scale).
19.Patient with fewer than three bowel movements per week in the 2-week run-in period
20.Pregnant woman as determined by the positive pregnancy test result
21.Patient who has recently experienced lactose intolerance.
22.Patient with abnormal laboratory test or positive stool cultures (e.g., C. difficile, ova and parasites, Camplylobacter, E. Coli 0157:H7, Yersinia, Salmonella, Shigella), which is judged to be clinically significant.
23.Patient who takes contraindicated concomitant drugs (see Appendix 1)
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| E.5 End points |
| E.5.1 | Primary end point(s) | ·Responder rate of global assessment of relief of overall IBS symptoms during the last 4 weeks of treatment
·Responder rate of global assessment of relief of abdominal discomfort/pain during the last 4 weeks of treatment
Definitions of responder:
IBS symptoms relief: Patient-reported Global assessment of relief of overall IBS symptoms (question #10 in Appendix 4) with a score of 0 or 1 for at least 2 weeks of the last 4 weeks treatment.
Abdominal discomfort/pain relief: Patient-reported Global assessment of relief of abdominal discomfort/pain (question #11 in Appendix 4) with a score of 0 or 1 for at least 2 weeks of the last 4 weeks of treatment.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
