The study compound may potentially be used for the treatment of heart and vascular diseases and metabolic diseases. In metabolic diseases, something goes wrong with the conversion of nutrients into energy, or nutrients are not properly broken down. Heart and vascular diseases and metabolic diseases are a group of long-term diseases.

The study consists of four parts: Part A, Part B, Part C and Part D. You can only participate in one part.

In all parts of this study, we will investigate how safe the study compound is and how well it is tolerated. We will also investigate how quickly and to what extent the study compound is absorbed, transported, and eliminated from the body. In addition we will also look if the study compound has an effect on an important protein involved in inflammation. In part C, we will also investigate how quickly and to what extent the study compound is absorbed, transported, and eliminated from the body, but then during fed or fasted conditions.

In Part A and B, we will compare the effects of the study compound with the effects of a placebo. A placebo is a compound without any active ingredient.

You will be given the study compound (or placebo) as capsules by mouth with water. In part C, 2 hours after administration of the first dose of capsules, you will receive a solution of the study compound directly into a blood vessel. In part D, after administration of the first dose of capsules, you will also receive a small drink containing the study compound.

In Part A, you will receive the study compound once. In part B, you will receive the study compound once daily for 7 days. In Part C, you will receive the study compound twice as capsules by mouth and once directly in a blood vessel. In Part D, you will receive the study compound twice as capsules by mouth and once as a small drink.

In part C and D, the study compound will be labeled once as a radioactive (14C). Radioactively labeling a compound is done to be able to study how quickly and to what extent the compound is absorbed, converted and excreted by the body. The radioactivity disappears from the body at the same time as the compound through the feces, urine and/or breath. The compound has a radiation burden which is less than from the natural background radiation that you are exposed to in the Netherlands in 1 month. This background radiation is released from space, soil, air, water, food and construction materials. To measure radioactivity levels in your body, blood, urine and feces will be collected during the trial.

During Part A and B, your heart will be monitored continuously from 18 hours before administration of the study compound until 36 hours (Part A) or 48 hours (Part B) thereafter. You will have sticky patches (electrodes) attached to your chest that are connected to a device. At various times, you will have to lie still for 10 minutes without moving, talking or sleeping. You also cannot listen to music, watch TV or use a laptop or phone. However, apart from these times, you may do so.

In part B, your eyes will be checked at two visits. The first eye examination will take place during a second screening visit, and the second eye examination during the study itself. These examinations will be done by a trained eye care professional. As part of the eye examination, you will receive eye drops to dilate your pupils. This will make you more sensitive to light and may cause temporary blurred vision. Therefore, you must not drive a car for at least 3 hours after such an eye examination.

In Part C, you will receive the study compound once with breakfast and once without breakfast. The order in which this will occur will be determined by chance. In one period you will receive a high-fat breakfast with a standard composition. You must start exactly on time and finish it within 30 minutes. The entire breakfast must be consumed.

At the start of the screening, you should only have consumed water for 4 hours. This means that before your potential participation in the study, we will already ask you not to eat for a period of time. You have not yet signed the form for participation in the trial. After the screening it will be announced whether you can participate.

All (potential) medicines can cause side effects. Because the compound has not yet been administered to humans, there are currently no known side effects in humans. In rare cases (<0.1%), serious side effects can occur during the first administration to humans. The compound has already been extensively tested in the laboratory and on animals. Prior to the medical screening, you will receive written information about the trial, which also describes the possible side effects based on these animal tests. This information will also be discussed with you at the start of the medical screening. You can then ask the screening physician or nurse any question you may have. The medical screening will only take place after you have given written consent to participate in the trial. We want to emphasize that even after giving written consent, participation in any clinical trial is voluntary. You can decide at any time not to participate or to stop the medical screening or the trial. You do not need to provide a reason for why you no longer wish to participate.

You will receive a gross compensation of € 1731 for participation in Part A.
You will receive a gross compensation of € 3520 for participation in Part B.
You will receive a gross compensation of € 4355 for participation in Part C.
You will receive a gross compensation of € 6479 for participation in Part D.

Travel expenses will be reimbursed based on the distance traveled (€ 0.23 per kilometer) with a minimum of € 14.23 and a maximum of € 193.20 (840 kilometers) per round trip, regardless of the mode of transportation.