Metabolism and Pharmacokinetics of [14C]-DK-AH 269 CL in 12 Healthy Male Volunteers

Metabolism and Pharmacokinetics of [14C]-DK-AH 269 CL After Administration of Single Doses of 5 mg [14C]-DK-AH 269 CL Intravenously and 10 mg [14C]-DK-AH 269 CL as Oral Solution in a Parallel-group Design in 12 Healthy Male Volunteers

• To investigate absorption, metabolism and excretion of [14C]-DK-AH 269 CL after oral and intravenous administration in healthy volunteers
• To assess the safety and tolerability of DK-AH 269 CL after oral and intravenous administration to healthy volunteers

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C]-DK-AH 269 CL, solution for infusion; Drug: [14C]-DK-AH 269 CL, drinking solution

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 50 to 65 years of age
• Body Mass Index (BMI) of 19.9 to 29.9 kg/m2
• Resting heart rate (HR) (after 5 min. in the supine position) of more than 55 bpm
• All volunteers will have given their written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.

Exclusion Criteria:

• Any finding at the medical examination (including BP, HR and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, hematological/oncological, immunological or hormonal disorders
• Diseases of the central nervous system or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or 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
• Intake of drugs with a long half-life (> 24 hours) within ten half-lives of the respective drug before enrolment in the study
• Use of any drugs which might influence the results of the trial within two weeks prior to administration or during the trial
• Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial)
• Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation (≥ 100 mL within 2 months prior to administration or during the trial)
• Excessive physical activities (within the last week before the study)
• Any laboratory value outside the reference range and of clinical relevance
• Inability to comply with dietary regimen of study centre

Not necessarily clinically relevant abnormalities, but specific exclusion criteria for the drugs under study or for the study:

• Subjects at increased risk for development of cardiac arrhythmia (e.g. family history of long QT syndrome or sudden cardiac death)
• ECG: PR interval > 210 ms
• HR at rest ≤ 55 beats per minute (bpm)
• Relevant ophthalmological disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: [14C]-DK-AH 269 CL intravenous	Drug: [14C]-DK-AH 269 CL, solution for infusion
Experimental: [14C]-DK-AH 269 CL oral	Drug: [14C]-DK-AH 269 CL, drinking solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum measured concentration of the analytes in plasma (Cmax)		Up to 96 hours after start of treatment
Area under the concentration-time curve of the analytes in plasma (AUC)		Up to 96 hours after start of treatment
Time from dosing to the maximum concentration of the analytes in plasma (tmax)		Up to 96 hours after start of treatment
Terminal rate constant of the analytes in plasma (λz)		Up to 96 hours after start of treatment
Terminal half-life of the analytes in plasma (t1/2)		Up to 96 hours after start of treatment
Mean residence time of the analytes in the body after intravenous administration (MRT)		Up to 96 hours after start of treatment
Mean residence time of the analytes in the body after oral administration (MRTpo)		Up to 96 hours after start of treatment
Apparent clearance of the analytes in plasma following extravascular administration (CL/F)		Up to 96 hours after start of treatment
Total clearance of the analytes in plasma following intravascular administration (CL)		Up to 96 hours after start of treatment
Apparent volume of distribution of the analytes during the terminal phase λz following extravascular administration (Vz/F)		Up to 96 hours after start of treatment
Volume of distribution at steady state (Vss)		Up to 96 hours after start of treatment
Fraction of analytes eliminated in urine from 0 to the time of the last quantifiable data point (fe0-tz)		Up to 120 hours after start of treatment
Fraction of analytes eliminated in faeces from 0 to the time of the last quantifiable data point (fefaeces,0-tz)		Up to 120 hours after start of treatment
Renal clearance of the analytes from 0 to the time of the last quantifiable data point (CLR,0-tz)		Up to 120 hours after start of treatment
Fraction of dose absorbed, based on radioactivity data (Fa)		Up to 96 hours after start of treatment
Absolute bioavailability of the analytes after oral administration (F)		Up to 96 hours after start of treatment
Ratio of CBlood cells/Cplasma [14C]-radioactivity		Up to 96 hours after start of treatment
Number of patients with clinically significant findings in vital signs	blood pressure, heart rate	up to 12 days after last drug administration
Number of patients with clinically significant findings in 12-lead ECG		up to 12 days after last drug administration
Number of patients with clinically significant findings in 2-lead ECG (telemetry)		up to 90 minutes after start of treatment
Clinically significant changes from baseline in physical examination		Pre-dose, and 12 days after last drug administration
Occurrence of visual phenomena	questionnaire	up to 120 hours after start of treatment
Number of patients with clinically significant findings in clinical laboratory tests		up to 12 days after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: 503.209