Pharmacokinetics and Pharmacodynamics of BIWH 3 in Healthy Duffy Positive vs. Duffy Negative Male Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: BIWH 3

• Registration Number: NCT02249117
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Study to compare the pharmacokinetic and pharmacodynamic effects of escalating dosages of recombinant human pyro-Glu MCP-1 (BIWH 3) in Duffy positive vs. Duffy negative healthy male volunteers: plasma levels of monocyte chemotactic protein-1 (MCP-1) and markers of leukocyte, coagulation, platelet and endothelial activation will be quantified; To examine the safety of BIWH 3 in this setting

Detailed Description

Not available

Study Timeline

• Study Start: 2003-06
• Primary Completion: 2003-08
• Status Verified: 2014-08
• Study First Submitted: 2014-08-21
• Study First Submitted QC: 2014-09-23
• Last Update Submitted: 2014-09-23
• Study First Posted: 2014-09-25
• Last Update Posted: 2014-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 36

Inclusion Criteria

• Healthy male subjects as determined by results of screening
• Erythrocyte Fy positive and negative individuals because expression of the Duffy (Fy) receptor may influence MCP-1 plasma levels in humans
• Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
• Age ≥ 18 and ≤ 50 years
• Body mass index: ≥18 kg/m2 and < 30 kg/m2
• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory variables unless the investigator considers an abnormality to be clinically irrelevant
• Normal pharmacodynamic variables as determined at baseline visit
• Normal response to glucose tolerance test

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Exclusion Criteria

• Any finding in the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Current or history of: gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, autoimmune, hormonal disorders, diseases of the central nervous system (such as epilepsy), psychiatric disorders or cancer
• Symptoms of a clinically relevant illness in the 3 weeks prior to planned administration of study drug
• History of orthostatic hypotension, fainting spells and blackouts
• Chronic or relevant acute infections
• History of allergy / hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Any Electrocardiogram (ECG) value outside the reference range of clinical relevance including, but not limited to QRS interval > 110 ms or QTcB > 450 ms
• Intake of drugs with a long half-life (> 24 hours) within 1 month prior to planned administration of study drug
• Use of any drugs which might influence the results of the trial within 10 days prior to planned administration or during the trial
• Participation in another trial with an investigational drug within 2 months prior to planned administration or during trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
• Current or history of drug, alcohol, tobacco or caffeine abuse
• Blood donation within 1 month prior to planned administration or during the trial
• Excessive physical activities within 5 days prior to planned administration of study drug or during the trial
• Seropositivity for hepatitis B antigen (HBs-Ag), hepatitis C (HCV), HIV 1, or HIV 2 antibodies
• Weight over 95 kg

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
BIWH 3	BIWH 3	single escalating dose

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞)	up to 14 days after drug administration
maximum BIWH 3 plasma concentration (Cmax)	up to 14 days after drug administration
Area under the plasma concentration-time curve up to the last quantifiable plasma concentration (AUC0-tz)	up to 14 days after drug administration

Secondary Outcome Measures

Name	Time	Method
Activation of coagulation	up to 14 days after drug administration	Prothrombin fragment levels via an enzyme-immunoassay
Number of subjects with clinically significant findings in vital signs	up to 14 days after drug administration	blood pressure, pulse rate, body temperature
Number of subjects with clinically significant findings in ECG	up to 14 days after drug administration
Number of subjects with clinically significant findings in laboratory tests	up to 14 days after drug administration
Number of subjects with adverse events	up to 14 days after drug administration
Monocyte activation	up to 14 days after drug administration	Quantification of leukocyte surface markers by flow cytometry
Platelet cell activation	up to 14 days after drug administration	Quantification of soluble P-selectin by enzyme immunoassay
Endothelial cell activation	up to 14 days after drug administration	Quantification of soluble E-selectin by enzyme immunoassay
Inflammatory response	up to 14 days after drug administration	Quantification of mRNA expression of IL-1 by reverse transcriptase-polymerase chain reaction (RT-PCR)