Controlled clinical trial to investigate the efficacy and safety of MYRRHINIL-INTEST® versus placebo in patients with diarrhoea-dominant irritable bowel syndrome (IBS-D)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

REPHA GmbH Biologische Arzneimittel

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

7 Jul 2020 → ongoing

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514383-61-00

EudraCT number

2019-000307-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Proof of efficacy, safety and tolerability of MYRRHINIL-INTEST® versus placebo in the treatment of diarrhoea-dominant irritable bowel syndrome (IBS-D)

Conditions and MedDRA coding

Diarrhoea predominant irritable bowel syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients of both sexes aged ≥ 18 and ≤ 75 years
2. Confirmed IBS-D diagnosis at visit 1
3. Colon examination (colonoscopy) performed on patients > 55 years of age within the past 5 years prior to participation in the study
4. Stool frequency: Before visit 1 (screening) in the last 7 days on at least 3 days 1 watery bowel movement/day.
5. Assessment of IBS-D symptoms: a) NRS pain > 3 points on visit 1 and visit 2 b) Stool consistency documented by the patient using the Bristol stool form scale on visits 1 and 2
6. Stool samples for testing for the absence of blood in the stool (occult blood test) and the absence of a Clostridioides (formerly Clostridium) difficile infection by means of glutamate dehydrogenase (GDH) ELISA upon inclusion in the study (result available at visit 2)
7. Presence of a declaration of consent signed by the patient
8. Consent that changes in lifestyle and dietary habits during the dietary habits will be avoided for the duration of the study
9. Willingness to keep a patient diary in accordance with the protocol
10. Negative pregnancy test for persons of childbearing potential

Exclusion criteria 42

1. Confirmed diagnosis of microscopic colitis, ulcerative colitis or Crohn's disease
2. Confirmed diagnosis of IBS of the constipation subtype (IBS-C), mixed IBS (IBS-M), or undefined IBS (IBS-U) according to Rome IV criteria
3. present since the onset of the disease a) Weight loss within the past 6 months (clinically significant, at the discretion of the investigator's judgement) b) Nocturnal symptoms (e.g. abdominal pain, diarrhoea) c) History of 1st degree relatives with colon carcinoma
4. suspicion of acute appendicitis
5. If faecal tests were performed in the 6 months prior to inclusion in the study were performed: a) Positive test for blood in faeces except: (Impurities due to haemorrhoids documented by a digital rectal examination or proctoscopy/ Traces of blood due to local irritation caused by frequent defecation (detected by local inspection inspection or a digital rectal examination) b) Positive test for parasites and worm eggs c) Clinically relevant elevated calprotectin levels (> 50 μg/g) in the stool
6. Diagnosed infectious gastroenteritis
7. known abnormalities of the gastrointestinal tract (e.g. megacolon) or known diseases diseases that result in an altered gastrointestinal passage (e.g. colon polyps)
8. functional disorders of the liver or kidneys (serum creatinine, serum AST or ALT at least 3-fold above the specified reference value in the last 12 months before inclusion in the study)
9. patients with known or suspected gallbladder inflammation (cholecystitis), gallstones, bile acid leakage syndrome, obstruction of the bile ducts or other diseases of the gallbladder gallbladder, dysfunction of the sphincter of Oddi or abdominal adhesions
10. past or suspected pancreatitis, ileus or gastrointestinal haemorrhage
11. female patients with known endometriosis
12. patients with gastroesophageal reflux disease (GERD) greater than or equal to 2b
13. known or suspected other causes of diarrhoea: coeliac disease, fructose, lactose, lactose, sorbitol intolerance or other intolerances that lead to diarrhoea symptoms diarrhoea
14. patients with malignant diseases or cancer treatments of the gastrointestinal tract in the last the last 5 years, as well as all other areas of the body in the last 2 years before Inclusion in the study with continued risk potential
15. known autoimmune diseases in the area of the gastrointestinal tract
16. immunocompromised patients (patients with organ transplants, patients with known HIV infection, etc.)
17. condition after partial colon resection
18. known diabetes mellitus, type I and/or type II
19. inappropriate medication for known hyper- or hypothyroidism, Hashimoto's thyroiditis or signs of thyroid dysfunction according to the blood values from Visit 1 and at the discretion of the investigator.
20. Hypersensitivity to camomile, other compositae, myrrh, coffee charcoal or any other component of the test medication MYRRHINIL-INTEST® or the placebo
21. patients with the rare hereditary fructose/galactose intolerance, glucose/galactose malabsorption or sucrase malabsorption. malabsorption or sucrase-isomaltase insufficiency
22. diagnosed severe somatic/psychosomatic, neurological and/or psychiatric disorders psychiatric disorders that make it difficult for the patient to make an informed decision about consent to participate in the clinical trial. The judgement is at the discretion of the treating investigator
23. Intake of neuroleptics up to 1 month before the start of the study and during participation in the study
24. Intake of antibiotics within the last 10 days before the start of the study and/or during study participation
25. Intake of systemic corticosteroids up to 1 month before the start of the study and during study participation participation in the study
26. Intake of medication for the treatment of IBS-D (including herbal and probiotic medication) at the time of visit 1 and during participation in the study (with the exception of study medication and emergency medication)
27. Continuous intake of NSAIDs (non-steroidal anti-inflammatory drugs, e.g. ibuprofen) for a period of more than 14 days (with the exception of NSAIDs used as medication to prevent thrombosis [e.g. ASA] or for the treatment of adverse events).
28. Intake of opioids (e.g. morphine, tilidine, tramadol, etc.) up to 1 month before the start of the study and during participation in the study
29. Intake of cardiac glycosides
30. Patients who participated or are participating in other drug trials (screening) 30 days prior to initial enrolment, or have previously participated in the same study (including randomisation)
31. Patients with a medical condition or in a situation which, in the opinion of the investigator, exposes the patient to a significant risk, interfere with the study results or significantly influence the study results
32. Signs or symptoms of an incipient bacterial or viral infection associated with fever (> 38.5 °C)
33. Abnormal laboratory values (clinically significant, i.e. more than threefold deviation of the upper or lower normal limit of the laboratory or significant at the discretion of the investigator)
34. Deviating forms of food intake: a) Need for artificial nutrition b) Use of formula diets c) parenteral nutrition
35. Existing alcohol abuse or abuse of medication or drugs
36. Pregnant women, nursing mothers or persons of childbearing potential who are unable to use a reliable method of contraception (Pearl Index < 1)
37. Legal incapacity and/or other circumstances that prevent the patient from understanding the nature, aim and effects of the study
38. Persons who have been institutionalised on the basis of an official or court order
39. Uncooperative patients
40. Persons incapable of giving consent
41. Patients who do not have sufficient command of the German language (informed consent)
42. Patients who are dependent on the sponsor, investigator, other study personnel or the trial site

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy will be assessed by a co-primary endpoint defined by the responder criteria: Responder rate (decrease in abdominal pain by at least 30%, decrease in days with at least one stool of consistency 6 or 7 by at least 50%)

Secondary endpoints 15

1. Change in stool frequency in the last 14 days of the treatment phase compared to the 14 days of the screening phase, each measured as the total number of stools. The target parameter is the reduction: Frequency pre-treatment - Frequency post-treatment.
2. Number of spontaneous defecations, recorded daily based on the entries in the patient's diary.
3. Stool consistency on individual days measured using the Bristol Stool Form Scale, recorded daily in the patient's diary, assessed during visits 1 to 6 at the study center.
4. Number of occurrences of the feeling of incomplete defecation, recorded daily in the patient's diary.
5. Assessment of the severity of IBS-D symptoms using the IBS-Severity Scoring System (IBS-SSS) during visits 1 to 6 (assessed by the patient).
6. Occurrence of mucus and/or blood in the stool on individual days, recorded daily in the patient's diary, assessed during visits 1 to 6 at the study center.
7. Determination of quality of life using the IBS-QoL questionnaire during visits 1 to 6 (assessed by the patient).
8. Global assessment of efficacy by the investigator and the patient during visits 3 to 6 (4-point scale).
9. Reduced use of rescue medication (Buscopan®) over the period from day 0 to 28 for the treatment of IBS-D symptoms and over the period of treatment phase 2.
10. Compliance (amount of study medication consumed) on visits 3 - 6, based on documentation in the patient diary
11. Compliance (amount of study medication consumed) via drug accountability at visits 4 and 6
12. Adverse events (AEs) throughout the course of the study (V2 - V6)
13. Vital parameters (blood pressure, pulse, body temperature) on V1 - V6
14. Clinical chemistry and haematology on V1, V4 and V6
15. Assessment of tolerability by investigator and patient at visits 3 - 6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

REPHA GmbH Biologische Arzneimittel

Sponsor organisation

REPHA GmbH Biologische Arzneimittel

Address

Alt-Godshorn 87, Godshorn Godshorn

City

Langenhagen

Postcode

30855

Country

Germany

Scientific contact point

Organisation

REPHA GmbH Biologische Arzneimittel

Contact name

Repha GmbH

Public contact point

Organisation

REPHA GmbH Biologische Arzneimittel

Contact name

Repha GmbH

Third parties 1

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications