E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023003 |
E.1.2 | Term | Irritable bowel syndrome |
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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 assess intra-patient reproducibility of barostat assessments of colorectal sensory functions and compliance in irritable bowel syndrome (IBS) patients using repeated baseline barostat measurements • To assess which is the most robust colorectal sensory parameter to detect a treatment-related difference in colorectal perception using the ascending method of limits (AML) and random phasic distension (RPD) protocols
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E.2.2 | Secondary objectives of the trial |
• To evaluate whether a treatment-related difference in colorectal pressure thresholds for first sensation, first desire to defecate, urgency, discomfort and pain perception can be detected using the AML barostat protocol • To evaluate whether a treatment-related difference in sensory intensity ratings for gas, urgency, discomfort and pain can be detected using the RPD barostat protocol • To assess inter-site differences in the pressure thresholds for first sensation, first desire to defecate, urgency, discomfort and pain perception in the AML and in the sensory intensity ratings for gas, urgency, discomfort and pain in the RPD barostat protocol
Exploratory objectives: • To conduct exploratory studies to identify proteins (TRPV1; PGP9.5), peptides (CGRP; substance P) or genes (TRPV1 mRNA) in mucosal tissue samples and blood that are correlated with visceral hypersensitivity • To assess proportions of hyper-/normo-sensitive IBS patients in the study centers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Females aged 18-65 years. 2. A positive diagnosis of IBS according to the Rome III criteria: At least 3 months, with onset at least 6 months previously, of recurrent abdominal pain or discomfort associated with 2 or more of the following: •Improvement with defecation; and/or •Onset associated with a change in frequency of stool; and/or •Onset associated with a change in form (appearance) of stool - discomfort means an uncomfortable sensation not described as pain. 3. Subjects must either: •have been surgically sterilized (bilateral oophorectomy) or hysterectomized at least 6 months prior to screening. Surgical sterilization procedures or hysterectomy must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History / Current Medical Conditions form of the eCRF. •be postmenopausal, i.e. must have no regular menstrual bleeding for at least 1 year prior to inclusion. Menopause will be confirmed by a plasma 17ί-estradiol concentration of <20 pg/mL and a plasma FSH level of >40 IU/L. •female subjects of child bearing potential must be using a double-barrier local contraception, i.e. intra-uterine device plus condom, or diaphragm plus condom, from 1 week before dosing until the end of study. In addition, appropriate precautions will be taken (e.g. Informed Consent, detailed counseling, abstinence during study, and negative pregnancy tests at screening and each baseline, with repetition of pregnancy test at the end of study). 4. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
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E.4 | Principal exclusion criteria |
1. Pregnant or breast-feeding women. 2. Body mass index (BMI) of <18 or >35. 3. Smoking of greater than 10 cigarettes per day and/or urine cotinine > 200ng/mmol at screening. 4. History of or evidence for structural diseases/conditions that affect the gastrointestinal system including prior intestinal or colonic surgery (except appendectomy). 5. Other diseases or conditions that in the opinion of the Investigator significantly affect colorectal sensitivity; specifically patients with suspected idiopathic chronic constipation must not be included. 6. Evidence of occult blood at stool analysis, or history of rectal bleeding. 7. Using or planning to use drugs or agents during the study period that alter GI physiology and visceral perception such as laxatives, prokinetics, erythromycin, 5-HT3 antagonists, 5-HT4 agonists, narcotics, pain medication, antispasmodic agents, or serotonin re-uptake inhibitors or tricyclic antidepressants. 8. Use of intra-vaginal devices (e.g. tampons) during colorectal barostat procedures. 9. Using or planning to use drugs or agents during the study period that alter blood coagulation like warfarin, heparin, NSAIDs or aspirin. 10. Diabetes mellitus or poorly controlled thyroid disease (hypo- or hyperthyroidism). 11. Known gallstones; history of biliary colic pain; history of pancreatitis. 12. Any clinical evidence (including physical exam, ECG, laboratory tests) of significant intercurrent medical conditions such as cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic or of any disease that may interfere with the objectives of the study. 13. Clinically significant bradycardia with potential to interfere with procedure induced vagal tone (Investigators may be guided by a cut-off heart rate of < 50 bpm). 14. Psychosis, schizophrenia, mania or major psychiatric illness needing pharmacological treatment. Well-compensated depression does not exclude a potential subject. 15. Symptoms of a significant clinical illness in the preceding two weeks. 16. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 17. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 18. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Sensory threshold scales for first sensation, first desire to defecate, urgency, discomfort and pain (one scale for each sensation=4 scales total per barostat procedure) - VAS scales at 12, 24, 36 and 48 mmHg for gas, urgency, discomfort and pain (one scale for each sensation at each pressure=16 scales total per barostat procedure) - pressure Pr1/2 (mmHg) at half of the maximum observed volume during AML - IBS disease activity questionnaire |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 8 |