• You are a healthy male or female.
• You are at least 18 and at most 60 years old.
• Your weight is at least 50 kg and your Body Mass Index (BMI) is at least 18.0 and at most 32.0 kg/m2. 
• Only non-smokers (minimum 3 months non-smoking) are allowed to participate in this clinical study.
• In group 1b and 2b only heavy smokers (10 cigarettes or more per day) are allowed to participate. During your stay in our research facility you are allowed to smoke two cigarettes after every meal (breakfast, lunch and dinner) and before or at the end of a walk outside. This comes down to a maximum of 8 cigarettes per day during your period of stay. The use of e-cigarettes and vapes is not allowed.

Note:

• You cannot participate in the study if you have participated in another clinical study in the 30 days prior to the first compound administration in this clinical study (counting from the last follow up appointment in the previous study).
• To determine if you are suitable to participate in this study, you will undergo a medical screening. Depending on availability, this can be performed in Groningen or in Utrecht.
• As a female you can only participate if you are not pregnant, not breast feeding and meet one of the following conditions:
  • You are using hormonal contraception (for example the contraceptive pill or intra-uterine device containing hormones) in combination with a condom;
  • You are using a copper intra-uterine device in combination with a condom;
  • You have passed the menopause (no periods for at least 12 months);
  • You have been sterilized or your male partner has been sterilized;
  • You are not sexually active according to your lifestyle;
  • You are only sexually active with a partner of the same sex.
• As a male you can only participate if you meet one of the following conditions:
  • You are using a condom in combination with an additional contraception method used by your female partner;
  • You have been sterilized or your female partner is sterilized or has passed the menopause (no periods for at least 12 months);
  • You are not sexually active according to your lifestyle;
  • You are only sexually active with a partner of the same sex.

• Part 1 of the study consists of 1 period during which you will stay in the research facility in Groningen (location van Swietenlaan 6) for 28 days (27 nights), followed by a follow up call.
• Part 2 and part 3 of the study consist of 1 period during which you will stay in the research facility in Groningen (location van Swietenlaan 6) for 24 days (23 nights), followed by a follow up call.
• Part 4 of the study consists of 1 period during which you will stay in the research facility in Groningen (location van Swietenlaan 6) for 23 days (22 nights), followed by a follow up call.

Note: You must be available for all dates to be able to participate in this clinical study.