E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
refractory diarrhea after normal extended work-up to exclude causes of diarrhea not or not enough responding to standard anti-diarrhetics as evaluated by the investigator |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012727 |
E.1.2 | Term | Diarrhea |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to assess the effect of lanreotide autogel 120 mg on stool frequency in subjects with refractory diarrhea at day 28 (mean of last 7 days) compared to baseline. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of lanreotide autogel 120 mg on Quality of Life (QOL) at day 21, 28, 49 and day 56 in comparison to baseline.
To assess the effect of lanreotide autogel 120 mg on the consistency of the stools at day 28 and day 56 compared to baseline.
To assess the effect of lanreotide autogel 120 mg on the number of stools in subjects with refractory diarrhea at day 28 and day 56 (mean of last 7 days) compared to baseline.
To assess the effect of lanreotide autogel 120 mg on the normalization of stool frequency in subjects with refractory diarrhea at day 21, day 28, day 49 and day 56.
To assess the effect of lanreotide autogel 120 mg on stool frequency in subjects with refractory diarrhea at day 49 compared to baseline.
To document the etiology of refractory diarrhea.
To investigate the safety and tolerability of 2 doses of lanreotide autogel 120 mg.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must fulfill the following:
•Male or female subject with a refractory diarrhea (> 3 stools / 24 hours) for at least 1 month, after normal extended work-up to exclude causes of diarrhea (such as duodenum scopy with biopsies, ileocolonscopy with biopsies, 72 hours stool collection, bile acid breath test and normal thyroid function), not or not enough responding to standard anti-diarrhetics (probiotics, astringents, absorbents and transit inhibitors or any combination) as evaluated by the investigator
•Subject having discontinued anti-diarrheic treatment (these are, but are not limited to, probiotics, astringents, absorbents and transit inhibitors or any combination) at screening
•Subject having provided written informed consent prior to any study related procedures
•Subject of 18 years and older
•Subject mentally fit for completing a diary
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E.4 | Principal exclusion criteria |
Subjects will not be included in the study if the subject:
•Has already received a treatment with somatostatin analogues for the treatment of refractory diarrhea,
•Has received a treatment with somatostatin analogues for any other indication
within the last 6 months before study entry,
•Had a weight of stool < 600 g in the last 72 hrs stool collection,
•Has received a treatment with laxatives within the last week before study entry,
•Suffers from IBS with alternating bowel habits and predominant constipation,
•Suffers from infectious and/or inflammatory gastro-enteritis (colitis ulcerosa,
crohn´s disease and macroscopic colitis),
•Has a known intolerance to lanreotide or other somatostatin analogues,
•Is at risk of pregnancy or lactation, or is likely to father a child during the
study. Females of childbearing potential must provide a negative pregnancy
test at start of study and must be using double barrier or injectable
contraception. Non childbearing potential is defined as post-menopause for at
least 1 year, surgical sterilisation or hysterectomy at least three months before
the start of the study,
•Has abnormal baseline findings or any other medical condition(s) that, in the
opinion of the Investigator, might jeopardise the subject’s safety or decrease
the chance of obtaining satisfactory data needed to achieve the objective(s) of
the study,
•Was treated with any other investigational drug within the last 3 months before study entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint and Evaluation
A minimum reduction of 50 % or normalization (≤ 3 stools / 24 hours) in the mean number of stools recorded during the seven days period immediately prior to Day 28, or early termination (if before day 28), compared to the mean of seven day period prior to baseline visit.
Secondary Efficacy Endpoints and Evaluations
1. Change in QOL (assess using SF-36 and IBS-QOL) at Day 21, 28, 49 and 56 compared to baseline.
2. Change in median score of stool consistency (Bristol Stool Form Scale) recorded during the seven day period immediately prior to Day 28, and Day 56 or early termination compared to the mean of seven day period prior to baseline visit.
3. Percent change in mean number of stools recorded during the seven day period before Day 28 and Day 56 compared to the mean of seven day period prior to baseline visit.
4. Percentage of normalized subjects (=subjects with ≤ 3 stools per 24 hours) at Day 21, at Day 28, Day 49 and Day 56 or at early termination visit (according to the seven day period before each considered assessment).
5. Minimum reduction of 50 % or normalization (≤ 3 stools / 24 hours) in the mean number of stools recorded during the seven day period immediately prior to Day 49 or early termination compared to the mean of seven day period prior to baseline visit.
6. Documentation of etiology of refractory diarrhea. Percentage & number of subjects with same etiology.
The primary criterion for the assessment of safety will be an investigation of the incidence of adverse events.
The other safety endpoints are: vital signs and clinical examination findings.
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 18 |
E.8.5 | The trial involves multiple Member States | No |
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
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The end of the trial is defined as the last visit of the last patient 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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |