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    Summary
    EudraCT Number:2009-015166-62
    Sponsor's Protocol Code Number:EME-08/43/15
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-10-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2009-015166-62
    A.3Full title of the trial
    A randomised controlled trial of Losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the effects of Losartan in patients with non-alcoholic steatohepatitis.
    A.3.2Name or abbreviated title of the trial where available
    Fibrosis Effects of Losartan in Nash Evaluation Study- FELINE
    A.4.1Sponsor's protocol code numberEME-08/43/15
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN57849521
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01051219
    A.5.4Other Identifiers
    Name:REC RefNumber:10/H0904/8
    Name:NIHR CSPNumber:37194
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNewcastle upon Tyne Hospitals NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNIHR, Efficacy, Mechanism and Evaluation Programme
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Cozaar
    D.2.1.1.2Name of the Marketing Authorisation holderMerck, Sharp and Dohme Limited
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameLosartan
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLosartan Potassium
    D.3.9.1CAS number 114798-26-4
    D.3.9.3Other descriptive nameLosartan
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Fibrosis in patients with non-alcoholic steatohepatitis.
    E.1.1.1Medical condition in easily understood language
    Accumulation of tough scar tissue in the liver in patients with non-alcoholic steatohepatitis.
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10053219
    E.1.2Term Non-alcoholic steatohepatitis
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The principal research question/objective is to determine whether Losartan, taken as a tablet (50mg once a day) versus a dummy pill (which will look exactly the same as the real medication) is effective at slowing down, halting or reversing liver fibrosis (scar tissue) in patients with non-alcoholic steatohepatitis.
    E.2.2Secondary objectives of the trial
    The secondary research questions/objectives are: 1. to determine whether Losartan can prevent clinical deterioration in NASH, or impact on the quality of life. 2. to show any changes in serum (blood sample), radiological (fibroscan) or histological (liver tissue) samples giving an indication to disease progression. 3. to measure the change in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) from baseline. 4. to note responder rate for placebo versus intervention.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria: Adults (aged 18+ years), with steatohepatitis and fibrosis (Kleiner F1-F3), resulting from non-alcoholic fatty liver disease.
    E.4Principal exclusion criteria
    Exclusion criteria: 1. refusal or inability (lack of capacity) to give informed consent 2. average alcohol ingestion more than 21 units per week (males) or more than 14 units per week (females) 3. history or presence of Type 1 diabetes mellitus 4. haemoglobin A1C >15.0 5. other causes of chronic liver disease or hepatic steatosis 6. any contra-indication to liver biopsy 7. history of or planned gastrointestinal bypass surgery 8. hepatocellular carcinoma 9. previous liver transplant 10. recent significant weight loss (more than 5% total body weight within last 6 months) 11. electrolyte disturbance: potassium level outside the normal (local) range. 12. ALT or AST > 10 x ULN at screening 13. recent (within six months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis (corticosteroids, amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid), or concomitant use of pioglitazone, fluconazole, rifampicin or any drug contra-indicated in the Losartan Summary of Product Characteristics (SmPC) 14. Introduction of metformin, glitazones, a GLP-1 agonist, Vitamin E or C, betaine, s-adenosyl methionine, ursedeoxycholic acid, silymarin, fibrate, pentoxifylline, orlistat, sibutramine or rimonabant within 3 months of baseline liver biopsy and screening visit. 15. intolerance of ARBs or presence of multiple allergic reactions to drugs 16. use of ACE inhibitor or ARB in previous year 17. hypotension (Systolic less than 100, diastolic less than 60) 18. renal failure (Cr >130) 19. participation in any clinical study of an investigational medicinal product (IMP) within 30 days or five half-lives of the IMP, whichever is longer 20. presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, renal, hepatic, metabolic, haematological, neurological, psychiatric, systemic, ocular, gynaecological or any acute infectious disease or signs of acute illness that, in the opinion of the investigator, might compromise the patient’s safe participation in the trial 21. presence or history of cancer within the past five years, with exception of adequately-treated localised basal cell carcinoma of the skin, in situ cervical carcinoma or solid malignancy surgically excised in toto without recurrence for five years 22. women of child-bearing potential not protected by effective contraceptive method of birth control or surgical sterilization, and/or who are unwilling or unable to be tested for pregnancy (Pregnancy status will be checked by serum pregnancy testing before initiation of study treatment and by urine pregnancy testing during the trial) 23. known allergy or sensitivity to Losartan or its excipients (microcrystalline cellulose (E460); lactose monohydrate; pregelatinized maize starch; magnesium stearate (E572); hydroxypropyl cellulose (E463); hypromellose (E464))
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome will be change in Kleiner fibrosis score, [Kleiner DE et al, Hepatology 2005], based on histological fibrosis stage (as judged by two independent blinded histopathologists, from liver biopsies), from pre-treatment to end-of-study (ie. 96 weeks follow-up).
    E.5.1.1Timepoint(s) of evaluation of this end point
    This endpoint measured at visit 8 (96 weeks).
    E.5.2Secondary end point(s)
    Secondary outcomes are: changes in radiological (Fibroscan) assessment. changes in serological (Enhanced Liver Fibrosis - ELF and Fibromax). change in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) - determined by liver biopsy.
    E.5.2.1Timepoint(s) of evaluation of this end point
    This endpoint measured at visit 1 (screening), 48 & 96 weeks. NAS (liver biopsy) measured prior to study entry and at 96 weeks.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned30
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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 trial will be the last patient's last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months42
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 214
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state214
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 214
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Continuation of the study medication after the trial will be decided by the patient's doctor, based on evidence from the trial and clinical condition of the patient.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Northumberland, Tyne and Wear CLRN
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2010-11-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-03-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-12-31
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