Elafibranor Pharmacokinetic Parameters in Elderly Healthy Volunteers

Inclusion criteria

• For All Participants:

• Provide written informed consent prior to the conduct of any study related procedures;
• With a minimum body weight (BW) of 50 kg and within a Body Mass Index (BMI) range of 18.0 to 30.0 kg/m^2 (all inclusive) at Screening visit;
• Medically healthy as determined by the Investigator or medically qualified designee at both Screening and Inclusion visits. This will include no variation of BW of more than 5 percent between Screening and Inclusion visits;
• Absence of clinically relevant abnormalities identified by a detailed medical history and complete physical examination;
• Healthy participants, as determined by Normal Blood Pressure (BP) and Heart Rate (HR) at the screening and Inclusion visits after 5 minutes in supine position;
• Normal ECG recording on a 12-lead ECG at the screening and Inclusion visits and no sign of any trouble of sinusal automatism, or considered as non clinically significant by investigator;
• Laboratory parameters within the normal range of the laboratory;
• Able to comprehend and willing to sign an Informed Consent Form, and to abide by the study restrictions;
• Non-smoker participant or smoker of not more than 5 cigarettes/day within 3 months prior to Inclusion visit, and able to restrain from smoking during the whole study duration;
• Participant with normal dietary habits;
• Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research;

• For Healthy Young Volunteers only:
• Males or females, between 18 and 45 years of age (all inclusive) at screening;
• Matched to healthy elderly participants by BMI (plus or minus 20 percent) and gender;
• Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment;
• Females of childbearing potential must have a negative qualitative serum pregnancy test at Screening visit and a negative urine pregnancy test at Inclusion visit;

• For Elderly volunteers only:
• Males or females aged 75 years old or older at Screening visit;
• Participants with mild, chronic, stable disease and stable treatment dose - no change in dose for the 3 months prior to Screening visit - (hypertension, hyperlipidemia, osteoarthritis, treated benign prostate hypertrophy, stable and treated hypothyroidism, treated glaucoma);
• Participants with suitable veins for cannulation or repeated venipuncture.

Exclusion criteria

• For all participants:

• Participants with a history of noncompliance to medical regimens;
• Participant who, in the opinion of the Investigator, is likely to be not respectful or not cooperative during the study, or unable to cooperate because of a language problem or a mental deficiency;
• Participant who cannot be contacted in case of emergency;
• Participant who is in the exclusion period of a previous study;
• Administrative or legal supervision;
• Inability to abstain from intensive muscular effort;
• Participant who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study;
• A positive alcohol test result or urine screen for drugs of abuse result at Screening or Inclusion visits;
• Any history or suspicion of alcohol abuse;
• Any history or suspicion of consumption of any drug of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methamphetamines, methadone, methylenedioxymethamphetamine, opiates, tricyclic antidepressant), from screening to end of the study;
• Consumption of nutritional supplements, herb-containing drug preparations (including Chinese medicines) or other foods or beverages (e.g., grapefruit and xanthine-containing foods or beverages) that may affect drug-metabolizing enzymes or transporters from screening to end of the study visit;
• Evidence or history of gastrointestinal, hepatic, or renal disease, surgery or resection that would potentially alter absorption, distribution, metabolism, or excretion of orally administered drugs;
• Participants who have clinically significant disease of cardiovascular, respiratory, renal, endocrine, hematological, gastrointestinal, neurological (central nervous system), psychiatric, systemic, infectious disorders or malignant tumor;
• General anesthesia within 3 months before administration;
• History or presence of allergy or unusual reactions to some drugs or anesthetics or known hypersensibility to the investigation product or its excipients;
• Major surgery within 28 days prior to Screening visit or major surgery planned within 6 months following participation to the study;
• Blood donation within 2 months before administration or blood donation planned during the study or within 2 months following participation to the study;
• Receipt of blood products within 2 months prior to Inclusion visit;
• Participants with symptomatic hypotension at Screening visit, whatever the decrease of blood pressure, or asymptomatic postural hypotension defined by a decrease in SBP ≥ 20 mmHg or DBP ≥ 10 mmHg within 3 minutes when changing from the supine to the standing position;
• Frequent headaches and/or migraines, recurrent nausea and/or vomiting;
• Participants who are positive for human immunodeficiency virus antibody, hepatitis B virus surface antigen, hepatitis C virus antibody;
• Significant, uncontrolled, or life-threatening condition or organ or disease;
• Show evidence of active renal disease (e.g. diabetic renal disease, polycystic kidney disease) or estimated glomerular filtration rate <60 mL/min/1.73m²;
• Evidence of pelvic organ prolapsed, incontinence, or fistula of the urogenital system;
• Have a history of syncope, presyncope, uncontrolled vertigo, postural dizziness, or at risk for falls, as judged to be clinically significant by the investigator;
• Any drug intake during the 2 weeks or 5 half-life of the drug preceding the first administration except those defined in concomitant medication section

• For Young Adults Volunteers only:
• Females who are pregnant or breastfeeding. Female participants should not be enrolled if they plan to become pregnant during the time of study participation;
• Any medications (except paracetamol 3g/day or contraception) intake within the 2 weeks or 5 half-life prior to Screening visit;
• Evidence or history of clinically significant metabolic or allergic disease.