Non-alcoholic fatty liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity MedDRA version: 25.0 Level: LLT Classification code 10082249 Term: Nonalcoholic fatty liver disease System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Is capable of understanding the written informed consent, provides signed written informed consent, is willing and able to complete the electronic diary (eDiary), and agrees to comply with protocol requirements. - Is an adult male or female, 18 to 70 years (both inclusive) of age. - Was diagnosed with NAFLD. - Presents with steatosis score of S1–S3 (defined as CAP score >248 decibels per meter [dB/m], as measured by transient elastography). - Presents with liver fibrosis score of F1–F3 (defined as LSM of 5-13 kilopascals [kPa], as measured by transient elastography). - Has confirmed diagnosis of at least one of the following associated illnesses: o T2DM and has been treated with diabetes medications (eg, metformin, insulin) with stable doses for 3 months, as judged by the investigator, before the patient enrollment visit, and is willing to continue their medications during the trial. o Hyperlipidemia (defined as presence of abnormally elevated levels of any or all lipids or lipoproteins in the blood) and has been treated with hyperlipidemia medications (eg, statins) with stable doses for 3 months, as judged by the investigator, before the patient enrollment visit, and is willing to continue their medications during the trial. o Obesity (defined as body mass index [BMI] =30 kg/m2).* *Body weight and height will be recorded for the calculation of BMI (metric: BMI = weight [kg]/[height (m)]2). - Is willing to follow lifestyle modification (diet and physical activity/exercise), as recommended by the investigator, and agrees to maintain these modifications during the trial period. (Note: In order to encourage stable and sustainable lifestyle modification among patients during the conduct of this trial, sites will be encouraged to apply site- and disease-specific SoC or apply 2016 European Association for the Study of the Liver [EASL] guidelines (EASL et al 2016). In either case, SoC refers to lifestyle modification, whose common denominator across trial sites potentially could be summarized as a measure to decrease body fat and weight.) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria (at the patient enrollment visit) will be excluded from the trial: - Has other causes of liver disease or abnormal laboratory results (AST =4 × upper limit of normal [ULN], ALT =4 × ULN, bilirubin =2 × ULN), or cirrhosis within 3 months before the patient enrollment visit. - Has current viral hepatitis. - Has been diagnosed with type 1 diabetes mellitus (T1DM). - Has an HbA1c >10.0% within 3 months before the patient enrollment visit. - Has severe heart disease (eg, heart failure), according to New York Heart Association (NYHA) Functional Classification (Class II–IV; The Criteria Committee of the New York Heart Association 1994) or severe renal impairment, as defined by estimated glomerular filtration rate of 20 g per day in women or >30 g per day in men. - Is enrolled in another clinical trial or has taken other investigational drug(s) within 1 month before the patient enrollment visit. - Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or potentially is at risk of noncompliance to trial procedures. - Has hypersensitivity to Essentiale or its components or any of its excipients that, in the opinion of the investigator, contraindicates participation in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Essentiale added to SoC (lifestyle modification [diet and physical activity/exercise]) compared with placebo added to SoC (lifestyle modification [diet and physical activity/exercise]) in patients with NAFLD associated with T2DM and/or hyperlipidemia and/or obesity. ;Secondary Objective: 1. To assess the QoL of patients with NAFLD associated with T2DM and/or hyperlipidemia and/or obesity. 2. To evaluate severity of 4 major symptoms in patients with NAFLD associated with T2DM and/or hyperlipidemia and/or obesity. 3. To describe the safety of Essentiale and placebo in patients with NAFLD associated with T2DM and/or hyperlipidemia and/or obesity.;Primary end point(s): The primary efficacy variable (change in steatosis, as measured by transient elastography [CAP score] from baseline to 6 months) will be analyzed using an analysis of covariance (ANCOVA) model with treatment arms, country, and CAP score at baseline as covariates. Difference between treatment arms and two-sided 95% CIs will be estimated within the framework of ANCOVA. As the ANCOVA only uses data information that includes patients with evaluable scores at baseline and 6 months, the actual population used in this analysis will be a subset of the mITT by default.;Timepoint(s) of evaluation of this end point: From baseline to 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints will be analyzed and summarized using descriptive statistics based on the mITT. There will be no sensitivity analysis for the secondary endpoints. The Holm procedure will be applied to address multiplicity issues while performing 5 statistical tests in total for 5 secondary endpoints. The corresponding 100*(1- 0.05/(m-(i-1))) CI will be provided. Note that the primary endpoint needs to be significant in order to interpret the tests related to secondary endpoints (hierarchical approach between the primary endpoint family and the secondary endpoints family). For each secondary endpoint listed below, the same approach as for the primary endpoint will be used on the mITT, except that the CAP score at baseline in the MMRM will be replaced by either the QoL total score at baseline or the symptom evaluation score at baseline (asthenia, feeling depressed, abdominal pain/discomfort, or fatigue), depending on which secondary endpoint is considered: • Change from baseline to 6 months in QoL total score of the CLDQ-NAFLD/NASH. • Change from baseline to 6 months in asthenia symptom score. • Change from baseline to 6 months in feeling depressed symptom score. • Change from baseline to 6 months in abdominal pain/discomfort symptom evaluation. • Change from baseline to 6 months in fatigue symptom score. ;Timepoint(s) of evaluation of this end point: From baseline to 6 months- 9 months (AEs, SAEs, including adverse events of special interest (AESIs)). | — |
Countries
Germany, Poland
Contacts
Public ContactGlobal Med.Lead,Consumer Healthcare
A. Nattermann & Cie. GmbH
Outcome results
None listed