| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Diarrhoea predominant irritable bowel syndrome |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10048571 |
| E.1.2 | Term | Irritable bowel syndrome aggravated |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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 |
Primary objective of this study is:
· To determine the efficacy of OMS210 8 mg and 32 mg bid in the treatment of IBS-D
based on patient’s global response to treatment (improvement in IBS symptoms). |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are:
· To compare OMS210 8 mg and 32 mg bid with placebo based on:
· Improvement in abdominal pain/discomfort
· Change from baseline in assessment of IBS symptoms
· Change from baseline in abdominal pain/discomfort
· Change from baseline in bloating/distension
· Change from baseline in urgency
· Change from baseline in Bristol Stool Scale score
· Improvement in quality of life (QOL) as measured by IBS quality of life
(IBS-QOL) total score
· To characterise the PK in patients with IBS-D. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A patient will be eligible for study participation if he/she meets the following criteria at both Visits 1 and 2:
1. Patient is male or female, aged 18 to 65 years, inclusive.
2. Patient has a diagnosis of IBS as defined by Rome III criterion. This criterion should be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. Recurrent abdominal pain or discomfort** at least 3 days per month in the last 3 months 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. Patient has at least one of the following criteria indicative of the diarrhoea predominant sub-type of IBS:
• More than three bowel movements a day
• Loose (mushy) or watery stools (type 5, 6 or 7 on the Bristol Stool Scale)
• Urgency (having to rush to have a bowel movement)
4. Patient has none of the following criteria, indicative of the constipation predominant sub-type of IBS:
• Fewer than three bowel movements a week
• Hard or lumpy stools (type 1 or 2 on the Bristol Stool Scale)
• Straining during a bowel movement
5. Patient is considered to be in otherwise good health in the opinion of the investigator, as determined by: a medical history with no clinically significant abnormalities, a pre-study physical examination with no clinically significant abnormalities and pre-study clinical laboratory findings within normal range, or if outside the normal range, not deemed clinically significant in the opinion of the investigator.
6. Patient is using stable lifestyle and dietary measures for treating IBS prior to study entry and will be able to maintain these throughout the study (if applicable).
7. All females of child-bearing potential must have a negative serum pregnancy test immediately prior to enrolment. In addition, all females of child-bearing potential must agree to be completely abstinent or be using an accepted form of contraception throughout the entire study period. Accepted forms of contraception are defined as those with a failure rate of < 1% when properly applied and include: combination oral pill and some intra-uterine devices, as guided by the investigator plus usage by the male partner of a condom and spermicide.
Female patients must also not be actively breast-feeding through the entire study period. For male subjects with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the follow-up visit. Adequate contraception is defined as the usage by the female partner of any form of hormonal contraception or intra-uterine device (which should be established prior to the start of the study), plus usage by the male partner of a condom and spermicide. The failure rate of the applied contraception should be less then 1% when properly applied.
8. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects.
9. Patient has the ability to co-operate with the investigator and to comply with the requirements of the entire study.
10. Patient is able to understand and voluntarily sign and date written informed consent prior to inclusion in the study.
11. Patient is willing to undergo colonoscopy with biopsy unless the same procedure has been performed in the last 3 years and results are available to exclude other possible causes of symptoms including, but not limited to, malignancy and colitis.
12. All patients will be assessed for celiac disease using the Celiac Disease Reflexive Panel. Test results must be negative for subject to be eligible.
|
|
| E.4 | Principal exclusion criteria |
A patient will not be eligible for study participation if he/she meets any of the exclusion criteria at Visit 1 and/or 2:
1. Patient has a known diagnosis of lactose intolerance or has had a previous positive hydrogen breath test (> 12 parts per million increase in hydrogen over fasting level).
2. Patient has any form of malabsorption, specifically celiac disease and exocrine pancreatic insufficiency of any aetiology.
3. Patient has any of the following red flag symptoms which are not typical of IBS: pain that awakens/interferes with sleep, diarrhoea that awakens/interferes with sleep, blood in the stool (visible or occult), weight loss, fever, clinically significant abnormal physical examination.
4. Patient has a history of lower GI bleeding in the last 2 years or has had an abnormal colonoscopy, flexible sigmoidoscopy, rectoscopy, anoscopy, protoscopy or abdominal ultrasound, unless further investigations have demonstrated a non-sinister cause.
5. Patient has uncontrolled or unstable abnormal thyroid function.
6. Patient has a positive test result for HIV, Hepatitis B or Hepatitis C at screening.
7. Patient has a history of pelvic floor dysfunction, severe constipation or faecal impaction or required manual evacuation to accomplish bowel movement.
8. Patient reports having any Type 1 or Type 2 stool on the Bristol Stool Scale during the screening period.
9. History of bariatric surgery or colonic surgery at any time. Appendectomy and cholecystectomy are acceptable if uncomplicated (no peritonitis) but these procedures must not have been undertaken within 12 months of screening.
10. Female patient with endometriosis.
11. Family history of colorectal cancer within first-degree relatives.
12. History of severe adverse reaction or severe hypersensitivity reaction to any drug.
13. Significant history of drug/solvent/alcohol abuse as per investigator’s assessments
14. Patient has a positive stool culture or presence of ova or parasites in the stool at screening.
15. Patient has donated blood or blood products (e.g., plasma or platelets) within the 3 months prior to screening.
16. Significant infection or known inflammatory process at baseline or in the 4 weeks prior to screening
17. Patient has any clinically significant medical history or ongoing findings that may include but are not limited to malignant tumours, multiple (> 3 at the same time or on separate occasions) or advanced adenomas, inflammatory bowel disease, diverticulitis, ischemic colitis, lymphocytic colitis or collagenous colitis. Patients
with diverticulosis may be included in the study provided their condition is stable and no clinically significant intervention for their condition has ever been required. Patients with mild to moderate anxiety and/or depression may be included in the study provided their condition is stable, inclusive of stable monotherapy.
18. Any other medical condition or investigations (including abnormal clinical laboratory tests) that in the Principal Investigator’s (PIs) opinion would make the administration of the study medication or study procedures hazardous to the patient or obscure the interpretation of AEs. Patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 2 x the upper limit of normal (ULN) must be excluded from the study.
19. Patient has participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
20. Concurrent use of prohibited medication
21. Male patient who intends to father a child while participating in the study.
22. Prisoners or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a psychiatric or physical (e.g., infectious disease) illness will not be allowed enrolment into the study.
23. Patients with a clinically significant history of, unstable or clinically significant cardiovascular disease such as, but not limited to, ongoing cardiac arrhythmia, cardiac insufficiency, hypokalemia, long QT syndrome or family history of long QT syndrome or QTcF greater than 450 ms prior to enrolment (patients with
uncomplicated, well controlled hypertension as judged by the Investigator, may be included).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of the study will be the proportion of responders in each treatment group, where a responder is defined as a patient who has a positive change from baseline of ≥ 1 point in self-reported assessment if IBS symptoms as measured by a 7-point Likert scale after 4 weeks of treatment. |
|
| 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 | 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 | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
| The end of the study will be defined as the last visit of the last patient in the study. |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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