Effects of Heme Arginate in Healthy Male Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Subjects, Heme Oxygenase, Genetic Polymorphism

Intervention / Treatment
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* Drug: saline solution
* Drug: heme arginate
* Drug: heme arginate
* Drug: heme arginate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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