RAS-Peptide-Profile Study in Healthy Male Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01771783
First received: January 16, 2013
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

The primary objective is the characterization of the RAS peptide profiles after single and repeated oral administration of a renin inhibitor, an ACE inhibitor and an angiotensin receptor blocker in healthy volunteers.

Secondary objectives are the correlation of RAS peptide profiles with pharmacokinetic profiles of the different RAS inhibitors and with pharmacodynamic parameters such as blood pressure and heart rate. Output of the classic RAS system will be assessed using aldosterone concentrations. Fluid and sodium intake will be monitored using sodium concentration and total volume in 24h urine.


Condition Intervention Phase
RAS Peptide Profile in Healthy Volunteers
Drug: ACEI-ARB-RI
Drug: ARB-RI-ACEI
Drug: RI-ACEI-ARB
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Single-center, Randomized, Open-label, 3-way Crossover Study to Characterize the RAS-peptide-profile After Single and Repeated Oral Administration of Different RAS-inhibitors in Healthy Male Subjects

Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • RAS-peptide profile [ Time Frame: 0-192h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood pressure and heart rate [ Time Frame: 0-192 h ] [ Designated as safety issue: No ]
  • Aldosterone concentrations [ Time Frame: 0-192 h ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: November 2012
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACEI-ARB-RI
angiotensin converting enzyme inhibitor (ACEI) angiotensin receptor antagonist (ARB) renin inhibitor (RI)
Drug: ACEI-ARB-RI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: ARB-RI-ACEI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: RI-ACEI-ARB
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Experimental: ARB-RI-ACEI
ARB-RI-ACEI
Drug: ACEI-ARB-RI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: ARB-RI-ACEI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: RI-ACEI-ARB
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Experimental: RI-ACEI-ARB
RI-ACEI-ARB
Drug: ACEI-ARB-RI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: ARB-RI-ACEI
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)
Drug: RI-ACEI-ARB
Other Names:
  • angiotensin converting enzyme inhibitor (ACEI)
  • angiotensin receptor antagonist (ARB)
  • renin inhibitor (RI)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01771783

Locations
Switzerland
Department Clinical Pharmacology, University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Manuel Haschke, PD Dr. med. Clinical Pharmacology, University Hospital Basel
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01771783     History of Changes
Other Study ID Numbers: USBMH-001
Study First Received: January 16, 2013
Last Updated: May 8, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
RAS-Peptide Profile
Renin-Angiotensin-System
Angiotensin-Converting-Enzyme-Inhibitor
Angiotensin-Receptor-Antagonist
Renin-inhibitor

Additional relevant MeSH terms:
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Angiotensin Receptor Antagonists
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014