RAS-Peptide-Profile Study in Healthy Male Subjects

The results of a pilot study have shown that single doses of different RAS inhibitors produce characteristic changes of the RAS peptide profiles. In a first step this finding needs to be verified in a larger number of healthy subjects. Since it is unknown, whether the changes that were observed within hours after a single inhibitor dose are stable over time, the profiles also need to be investigated under steady-state conditions of the different inhibitors. Comparison of RAS peptide profiles after single dose and under steady-state conditions will also allow to detect whether the peptide profiles are altered by compensatory mechanisms.

Inclusion criteria

• Male aged between 18 and 45 years (inclusive) at screening.
• Body mass index (BMI) between 18 and 28 kg/m2 (inclusive) and body weight at least 50 kg at screening.
• Systolic blood pressure (SBP) 100-140 mmHg, diastolic blood pressure (DBP) 60-90 mmHg and heart rate (HR) 45-90 bpm (inclusive), measured on the leading arm*, after 5 min in the supine position at screening.
• Signed informed consent prior to any study-mandated procedure.
• No clinically significant findings on the physical examination at screening.
• 12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening.
• Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study.

• leading arm right = writing with right hand

Exclusion criteria

• Smoking > 5 cigarettes per day
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Loss of ≥ 250 ml of blood within 3 months prior to screening.
• Treatment with an investigational drug within 30 days prior to screening.
• Previous treatment with any prescribed or over the counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of study.
• Legal incapacity or limited legal capacity at screening.
• Positive results from urine drug screen 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 drugs, or which might increase the risk for toxicity.
• Known hypersensitivity to any excipients of the drug formulations.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.