Mass Balance, Pharmacokinetics, and Metabolism of 14C-labeled ACT-128800 Administered to Healthy Male Subjects

Single-center, Open-label Study With 14C-labeled ACT-128800 to Investigate the Mass Balance, Pharmacokinetics, and Metabolism Following Single Oral Administration to Healthy Male Subjects

The study was conducted to investigate the metabolism and mass balance of ACT-128800, and to identify the elimination pathways (metabolism and excretion) of ACT-128800 and compare them with the known metabolic profiles of ACT-128800 in animals.

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure.
• Male and aged between 45 and 65 years (inclusive) at screening.
• No clinically significant findings on physical examination performed at screening.
• Body mass index (BMI) between 18-28 kg/m^2 (inclusive) at screening.
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 55-90 bpm (inclusive), measured on the leading arm, after 5 minutes in the supine position at screening. These criteria should also be met before the administration of the first dose.
• 12-lead electrocardiogram without clinically relevant abnormalities at screening.
• Clinical chemistry, hematology, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening.
• Negative results from urine drug screen at screening.
• Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria:

• Known hypersensitivity to any excipients of the drug formulation.
• Treatment with another investigational drug within the 3 months prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Smoking within the 3 months prior to screening.
• Any immunosuppressive treatment within 6 weeks before study drug administration.
• Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to screening.
• Loss of 250 mL or more of blood within the 3 months prior to screening.
• Lymphopenia (< 1,100 lymphocytes/μL).
• Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration.
• Positive hepatitis B or hepatitis C serology, except for vaccinated subjects, at screening.
• Positive human immunodeficiency virus serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.
• Exposure to artificial ionizing radiation (e.g., X-ray, thyroid scan, study with radiolabeled compound) in the 12-month period before screening.
• A history of clinically relevant constipation (defined as lasting more than 3 days) in the 4-week period before screening.