Effects of Heme Arginate in Healthy Male Subjects (HEMAHS)

Dose Escalation, Randomized, Placebo Controlled Study to Investigate the Effects of Intravenous Heme Arginate on Heme Oxygenase-1 (HO-1) and Heme Metabolism in Association With HO-1 Gene GTn Promoter Polymorphism in Healthy Male Subjects

Heme oxygenase 1 (HO-1) serves as a protective gene. It has been shown that one factor modulating HO-1 activity is a genetic variation in the HO-1 gene (functional GT length polymorphism in the promotor region). Heme arginate is a strong inducer of HO-1 as shown in several animal experimental studies. The aim of this clinical trial is to evaluate the HO-1 stimulation of heme arginate in healthy humans.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Genetic Polymorphism; Heme Oxygenase
• Intervention / Treatment: Drug: heme arginate; Drug: heme arginate; Drug: heme arginate; Drug: saline solution

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure.
• Male aged between 18 and 45 years (inclusive) at screening.
• No clinically significant findings on the physical examination at screening.
• Body mass index (BMI) between 18 and 28 kg/m2 (inclusive) at screening.
• 12-lead ECG without clinically relevant abnormalities at screening.
• Hematology, clinical chemistry, and urinalysis test 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 the study drug or any excipients of the drug formulation.
• Treatment with another investigational drug within 3 months prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to 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.
• Smoking within the last 3 months prior to screening.
• Previous treatment with any prescribed or OTC 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 3 months prior to screening.
• Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
• Positive results from the HIV serology at screening.
• Presumed non-compliance.
• Legal incapacity or limited legal capacity at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: P; Placebo	Drug: saline solution; intravenous infusion, single dose
Experimental: A1; 0.3 mg/kg heme arginate	Drug: heme arginate; intravenous infusion, single dose 0.3 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 1 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 3 mg/kg heme arginate
Experimental: A2; 1 mg/kg heme arginate	Drug: heme arginate; intravenous infusion, single dose 0.3 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 1 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 3 mg/kg heme arginate
Experimental: A3; 3 mg/kg heme arginate	Drug: heme arginate; intravenous infusion, single dose 0.3 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 1 mg/kg heme arginate; Drug: heme arginate; intravenous infusion, single dose 3 mg/kg heme arginate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The maximal HO-1 mRNA expression in PBMCs	2 months

Collaborators and Investigators

• Sponsor: Daniel Doberer

Publications and helpful links

Helpful Links

• Department of Clinical Pharmacology, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: May 16, 2008
• First Submitted That Met QC Criteria: May 21, 2008
• First Posted (Estimate): May 22, 2008

Study Record Updates

• Last Update Posted (Estimate): January 15, 2013
• Last Update Submitted That Met QC Criteria: January 13, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Other Study ID Numbers: EudraCT - 2007-003790-11