Clinical trial NCT03099785: Rifamycin SV-MMX® 600 mg Tablets Administered Three or Two Times Daily to Patients With IBS-D
Official title: A Phase II, Multicentre, Randomised, Double-blind, Placebo Controlled, Proof of Concept Study of Efficacy and Safety of Rifamycin SV-MMX® 600 mg Tablets Administered Three or Two Times Daily to Patients With Diarrhoea-predominant Irritable Bowel Syndrome (IBS-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diarrhea-predominant Irritable Bowel Syndrome
Lead sponsor: Cosmo Pharmaceuticals NV
Sponsor class: INDUSTRY
First posted: 2017-04-04
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety and efficacy Rifamycin SV-MMX® 600 mg tablets for patients with diarrhoea-predominant irritable bowel syndrome when administered two to three times daily.


Eligibility criteria: Inclusion Criteria:

1. Informed Consent: signed written informed consent before inclusion in the study
2. Sex and Age: males/females, ≥18 year old
3. IBS Diagnosis: confirmed IBS-D diagnosis per Rome IV criteria
4. Symptoms: active symptoms of IBS at baseline (day 1) as measured by average daily scores for at least 7 days before baseline:

   1. abdominal pain score ≥3 using an 11-point numeric rating scale and
   2. bloating score: 2-4 inclusive and
   3. stool consistency: score 6 or 7 (measured by the Bristol stool form scale) for at least 2 days from day -7 to day -1

      and by a negative response to the global IBS symptom assessment question and to the IBS-related bloating assessment question both given weekly during the screening phase up to day 1 before randomisation:
   4. "In the past 7 days, have you had adequate relief of your IBS symptoms?" \[No\] and
   5. "In the past 7 days, have you had adequate relief of your IBS symptom of bloating?"\[No\]
5. Colonoscopy: performed within 5 years; if patient's age \>50, colonoscopy performed within 2 years
6. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the study
7. Literacy: sufficiently literate to comply with the study requirement of using electronic diaries and filling in electronic forms
8. Contraception and fertility: females of childbearing potential and fertile males must be using at least one reliable method of contraception.

Reliable methods of contraception for women include:

1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
2. A non-hormonal intrauterine device \[IUD\] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit

   Reliable methods of contraception for men and male partners of female patients include:
3. Male condoms with spermicide

   Reliable methods of contraception for both women and men include:
4. A sterile sexual partner or sexual abstinence Women of non-childbearing potential or in post-menopausal status for at least 1 year and sterile or surgically sterilised men will be admitted.

For women of childbearing potential, serum pregnancy test result must be negative at screening

Exclusion Criteria:

1. IBS: symptoms of constipation at baseline:

   1. less than 3 bowel movements a week and
   2. stool consistency score ≤2 for ≥2 days in a week
2. Screening phase: failure to record the daily symptom assessments in the diary cards for at least 7 days before baseline
3. Gastroenteric: underlying gastrointestinal diseases including ulcerative colitis, Crohn's disease, pancreatitis, any active infectious, haemorrhagic or inflammatory disorder not related to IBS-D, gastrointestinal motility disorders such as ileus, gastroparesis or pseudoobstruction, gastroduodenal ulcer, gastrointestinal malignancy or potentially fatal diseases if not full in remission (5 years from diagnosis and without maintenance treatment), amyloidosis and cholelithiasis if cholecystectomy not performed
4. Intolerance: ascertained underlying lactose intolerance with response to diet or any other malabsorption syndrome with the exclusion of asymptomatic lactose malabsorption
5. Coeliac disease: ascertained or presumptive underlying coeliac disease
6. Bile: ascertained or presumptive bile acid malabsorption or bile acid induced diarrhoea
7. Diabetes: underlying diabetes type I or II
8. Thyroid: abnormal thyroid function not controlled by thyroid medications
9. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
10. Renal function: ascertained or presumptive clinically significant renal insufficiency or creatinine above twice the upper limit of normal (ULN) of the performing laboratory reference range
11. Liver function: chronic liver disease or clinically significant liver enzyme abnormality as evidenced by elevated AST, ALT or total bilirubin \>1.5 times ULN
12. AIDS/HIV: ascertained or presumptive acquired immunodeficiency (AIDS) or known infection with human immunodeficiency virus (HIV)
13. Diseases: significant history of medical or surgical conditions excluding hysterectomy, caesarean section, appendectomy, cholecystectomy, benign polypectomy and inguinal hernia and including renal, hepatic, cardiovascular, haematological, endocrine, immune, psychiatric or neurological diseases that in the investigator's opinion may interfere with the aim of the study; malignant diseases not in remission for at least 5 years
14. Medications: alosetron, eluxadoline, ondansetron, tegaserod, lubiprostone, warfarin, antipsychotic, antispasmodic, prokinetic, antidiarrhoeal, laxative, probiotic, narcotic or antibiotic agents within 14 days before the screening visit; antidepressant agents of the selective serotonin-reuptake inhibitor and tricyclic classes unless taken at a stable dose for at least 6 weeks before the screening visit
15. Investigational drugs: participation in the evaluation of any investigational product within 30 days before this study
16. Drug and alcohol: known history of drug or alcohol \[\>1 drink/day for females and \>2 drinks/day for males, defined according to the USDA Dietary Guidelines 2015\] abuse
17. Pregnancy (females only): pregnant or lactating women or wishing to become pregnant in the 3 months following this visit

Primary outcomes:
measure: Proportion of subjects with relief from abdominal pain and improved stool consistency.
timeFrame: 88 days
Secondary outcomes:
measure: Proportion of subjects with relief of global IBS symptoms during weeks 3-12 [Efficacy]
timeFrame: 10 weeks
measure: Proportion of subjects with monthly relief of global IBS symptoms [Efficacy]
timeFrame: 88 days
measure: Proportion of subjects with relief of IBS-related bloating during weeks 3-12 [Efficacy]
timeFrame: 10 weeks
measure: Proportion of subjects with monthly relief of IBS-related bloating [Efficacy]
timeFrame: 88 days
measure: Proportion of subjects with weekly relief of IBS symptoms, bloating and abdominal pain [Efficacy]
timeFrame: 88 days
measure: Number of weeks of IBS-symptom relief during follow-up [Efficacy]
timeFrame: 10 weeks
measure: Number of weeks of bloating relief during follow-up [Efficacy]
timeFrame: 10 weeks
measure: Change in IBS-symptoms, bloating and abdominal pain from baseline to 12 weeks - captured by a daily diary [Efficacy]
timeFrame: 12 weeks
measure: Proportion of monthly responders for IBS-symptoms, bloating and abdominal pain [Efficacy]
timeFrame: 3 months
measure: Change from baseline to each week during follow up for IBS-symptoms bloating, abdominal pain, stool consistency, urgency - captured by a daily diary [Efficacy]
timeFrame: 12 weeks
measure: Change from baseline at weeks 4, 8 and 12 in quality of life assessment [Efficacy]
timeFrame: 12 weeks
Other outcomes:
measure: Treatment Emergent Adverse Events [Safety]
timeFrame: 12 weeks
measure: Change from Baseline in Physical Exam [Safety]
timeFrame: 12 weeks
measure: Change from Baseline in Vital Signs [Safety]
timeFrame: 12 weeks
measure: Change from Baseline in Lab Tests [Safety]
timeFrame: 12 weeks
measure: Change from Baseline in ECG [Safety]
timeFrame: 12 weeks
Locations:
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg, Department of Gastroenterology
state: Herestraat 49
city: Brugge
country: Belgium
facility: St Lukas Ziekenhuis,
state: Lucaslaan 29
city: Bruxelles
country: Belgium
facility: Clinique universitaires Saint-Luc Gastroenterologie Route 606 Avenue Hippocrate, 10
city: Gent
country: Belgium
facility: Maria Middelares, Digestief Centrum, Buitenring St-Denijs 30
city: Gent
country: Belgium
facility: University Hospital Gent, Depintelaan 185
city: Berlin
country: Germany
facility: Emovis GmbH Wilmersdorfer Straße 79
city: Essen
country: Germany
facility: Unterfrintroper Hausarztzentrum Lehrpraxis der Universität Essen
city: Gauting
country: Germany
facility: Internistenzentrum Bahnhofstrasse 30
city: Hamburg
country: Germany
facility: Clinical Research Hamburg GmbH, Rahlstedter Bahnhofstraße 33
city: Hannover
country: Germany
facility: Gastroenterologie, Interventionelle Endoskopie, Diabetologie und Akutgeriatrie, KRH-Zentrumsgeschaftsfuhrer innere Medizin, KRK Klinikum Siloah-Oststadt-Heidehaus Stadionbrucke 4
city: Künzing
country: Germany
facility: Gemeinschaftspraxis Dr. Klein & J. Minnich
city: Leipzig
country: Germany
facility: AmBeNet GmbH, Wilhelm-Leuschner-Platz I2,
city: Magdeburg
country: Germany
facility: Universitatsklinikum Magdeburg A.O.R. Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Leipziger Str.44
city: Reinfeld
country: Germany
facility: Ärztehaus Reinfeld Praxisgemeinschaft für Allgemeinmedizin Klosterstraße 7
city: Rodgau
country: Germany
facility: Innomed Dr. med. Naudts Ludwig-Erhard-Platz 11
city: Weyhe
country: Germany
facility: Internistische Praxisgemeinschaft, Bereich Gastroenterologie Hauptstraße. 51
city: Aviano
country: Italy
facility: S.O.C Gastroenterologia Oncologica
state: PN
city: Cagliari
country: Italy
facility: Azienda Ospedaliera G. Brotzu, U.O. di Gastroenterelogia, Via Peretti
city: Milano
country: Italy
facility: Istituto Clinico Humanitas, Centro Malattie Infiammatorie Croniche Intestinali
city: Milano
country: Italy
facility: Fonazione IRCCS Ospedale Maggiore
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo, Dip Area Medica: Medicina Generale 1, Viale Camillo Golgi, 19
city: Roma
country: Italy
facility: Polo Scienze Gastroenterologiche ed
city: Roma
country: Italy
facility: Universita Campus Bio Medico, U.O.C di Gastroenterologia ed Endoscopia Digestiva
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato, Medicina Generale III- Gastroenterologia
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pijol (Can Ruti). Servicio de Aparto Digestivo Carretera de Canyet, s/n
state: Barcelona
city: Castellana
country: Spain
facility: Hospital Universitario La Paz, Servicio de Aparato Digestivo Po de la Castellana 261
state: Madrid
city: Colmenar Viejo
country: Spain
facility: Hospital Universitario Ramon Y Cajal, Servicio de Gastroenterologia y Hepatologia Ctra. de colmenar Viejo, Km 9,100
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari vall d'Hebron, Servicio de Aparato Digestivo, Passeig Vall d'Hebron, 119-129
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos, Servicio de Aparato Digestivo, Calle del Prof Martin Lagos, s/n,
Study officials:
References: