Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH)

AUC0-24 defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours.

Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

Population: Analysis was performed on PK population.

Cmax was defined as maximum observed plasma concentration.

Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

Population: Analysis was performed on PK population that included all participants who had received at least 1 dose of the study drug, did not had protocol deviations or adverse events (AEs) that significantly affected the PK, and had at least 1 post-dose PK sample.

Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.

Time frame: Pre-dose on Day 1 and 29

Population: Analysis was performed on PK population.

Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.

Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

Population: Analysis was performed on PK population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Tmax was defined as time to reach maximum observed plasma concentration.

Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

Population: Analysis was performed on PK population.

Fasting blood samples (collected after 10 hours fasting) were used to assess the following clinical chemistry parameters: creatinine, glomerular filtration rate, creatinine clearance, total proteins, albumin, electrolytes (sodium, potassium, chloride, calcium), uric acid, urea nitrogen, urea, creatine phosphokinase (CPK), AST, ALT, GGT, ALP, total and conjugated bilirubin, high sensitivity C-reactive protein, fasting plasma glucose, fasting insulin, HOMA-IR, fructosamine, C-peptide, free fatty acids, glycated hemoglobin A1c, cystatin C. Abnormal clinical chemistry values were classified based on reference range: lower limit of normality (LLN); normal (\>= LLN and \<= upper limit of normality \[ULN\]); \> ULN and \<3 ULN; \>=3 ULN and \<5 ULN and \>=5 ULN. Only the parameters for which at least one value of abnormality were reported and presented in this outcome measure.

Time frame: At Day 85 (i.e., end of treatment)

Population: Analysis was performed on safety population.

Fasting blood samples (collected after 10 hours fasting) were used to assess the following hematology and coagulation parameters: hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, prothrombin time (PT) and international normalized ratio (INR). Hematology and coagulation values were classified based on the reference range: LLN; normal (\>= LLN and \<= ULN); \> ULN and \<3 ULN; \>=3 ULN and \<5 ULN and \>=5 ULN.

Time frame: At Day 85 (i.e., end of treatment)

Population: Analysis was performed on safety population.

Blood samples were collected to assess the following urinalysis parameters: alpha-1 macroglobulin, N-acetyl glucosamide, neutrophil gelatinase-associated lipocalin, albumin, and creatinine. Abnormal urinalysis values were classified based on the reference range: LLN; normal (\>= LLN and \<= ULN); \> ULN and \<3 ULN; \>=3 ULN and \<5 ULN and \>=5 ULN.

Time frame: At Day 85 (i.e., end of treatment)

Population: Analysis was performed on safety population.

Vital signs were taken before any invasive procedures. Following vital signs were assessed: systolic blood pressure, diastolic blood pressure, heart rate. Abnormal vita signs was defined as any abnormal findings in the vital sign parameters and were categorized as 'abnormal, not clinically significant (NCS)' and 'abnormal, clinically significant (CS)'.

Time frame: At Day 85 (i.e., end of treatment)

Population: Analysis was performed on safety population.

ECG measurements were taken with the participants in resting position for at least 10 minutes. The investigator determined whether abnormal assessment results were clinically significant or not. The number of participants with abnormal clinically significant ECG findings were reported. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Day 85

Population: Analysis was performed safety population.

Physical examination findings were collected according to pre-defined body systems: general appearance; skin; eyes; ears; nose; throat; neck and thyroid; lungs; heart; upper/lower extremities; lymph nodes; abdomen; musculoskeletal system; basic neurological assessment. Additional systems were evaluated as needed. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care. Participants with at least one clinically significant abnormality in physical examination were reported and presented in this outcome measure. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on safety population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

An adverse event (AE) was any untoward medical in a participant or clinical investigation patient administered a pharmaceutical (investigational) product and which does not necessarily have to have a causal relationship with this treatment. A Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was another medically important condition. TEAEs were defined as AEs that started prior to first study drug dose and that worsened after, and the AEs that started on or after first study drug dose. TEAEs: Serious and non-serious AEs.

Time frame: From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)

Population: Analysis was performed safety population that included participants who had received at least one dose of study drug and had at least one post-baseline safety assessment.

The BMI for a given age (in years) and gender (male) was converted to an exact z-score. Given a participant's age, sex, BMI, and an appropriate reference standard, a BMI Z-score was determined. BMI Z-score \>=85th percentile was considered as overweight. Z-score was a statistical measure to describe whether a mean was above or below the standard. A Z-score of 0 was equal to the mean and is considered normal. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. Negative values are indicative of decrease in BMI (weight loss) and positive values are indicative of increase in BMI. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

The child, adolescent and parent/legal guardian PedsQL™ (Version 4.0) generic core scales was used to measure health-related quality of life (HRQOL). The response information was completed by the participant and by a parent/legal guardian individually. It consisted of 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). Items were scored on a 5 point Likert-type response scale: 0=never a problem to 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). Once scored, items were reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), where higher scores indicated better HRQOL. Total Scale Score was the sum of all the items over the number of items answered on all the Scales. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Day 85

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Waist circumference (in centimeters \[cm\]) was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Here, mIU/L was abbreviated as milli-international unit per liter.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (micro international units per milliliter \[mcIU/mL\]) \* fasting plasma glucose (mmol/L) / 22.5. A higher value indicates a greater insulin resistance. Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples to assess fibrinogen levels were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples to assess Haptoglobin level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples to assess Interleukin-6 level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples to assess plasminogen activator inhibitor-1 level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Here, IU/mL was abbreviated as International units per milliliter.

Time frame: Baseline (Day 1), Day 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Blood samples to assess Necrosis Factor Alpha level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.

Time frame: Baseline (Day 1), Days 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis. Normal range at screening: AST: 0 - 39 international units per liter (IU/L), ALT: 5 - 30 IU/L, GGT: 2 - 24 IU/L, and ALP: 74 - 390 IU/L.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific time points.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Baseline was defined as the last measurement before first intake of study treatment on Day 1.

Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113

Population: Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.