Study to Investigate the Effect of Paroxetine Mediated CYP2D6 Inhibition on the Pharmacokinetics of Tamsulosin in Healthy Male Volunteers

An Open Label Randomized Two-way Crossover Study to Investigate the Effect of Paroxetine Mediated CYP2D6 Inhibition on the Single Oral Dose Pharmacokinetics of Tamsulosin in Healthy Male Volunteers (CYP2D6 Extensive Metabolizers)

Study to investigate the effect of CYP2D6 inhibition by paroxetine on the single oral dose pharmacokinetics of tamsulosin and to investigate the effect on safety and tolerability

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Paroxetine; Drug: Tamsulosin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

All participants in the study are

• Healthy males
• Ranging from 21 to 50 years of age
• Body mass index (BMI) within 18.5 to 29.9 kg/m2
• In accordance with Good Clinical Practice (GCP) and the local legislation all volunteers will have given their written informed consent prior to admission to the study

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, clinically relevant electrolyte disturbances
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or clinically 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 (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study
• Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study
• Participation in another trial with an investigational drug (within 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 four weeks prior to administration or during the trial)
• Any laboratory value outside the reference range if indicative of underlying disease or poor health
• Excessive physical activities within the last week before the trial or during the trial
• Hypersensitivity to treatment medication and/or related drugs of these classes
• Non extensive metabolizer (EM) for CYP2D6

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamsulosin + Paroxetine; Tamsulosin: q.d on day 1 Paroxetine: higher dose q.d. on days -7 to 2 q.d., lower dose on days -10 to -8 and 3 to 5	Drug: Paroxetine; Other Names: Tagonis®; Drug: Tamsulosin; Other Names: Alna®
Active Comparator: Tamsulosin; Tamsulosin: q.d on day 1	Drug: Tamsulosin; Other Names: Alna®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of tamsulosin HCl in plasma)	up to 48 hours after dosing
AUC0-∞ (area under the concentration-time curve of tamsulosin HCl in plasma over the time interval from 0 extrapolated to infinity)	up to 48 hours after dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
tmax (time from dosing to the maximum measured concentration of tamsulosin HCl in plasma)	up to 48 hours after dosing
AUC0-tz (area under the concentration-time curve of tamsulosin HCl in plasma over the time interval from 0 to the last quantifiable data point)	up to 48 hours after dosing
λz (terminal rate constant of tamsulosin HCl in plasma)	up to 48 hours after dosing
t1/2 (terminal half-life of tamsulosin HCl in plasma)	up to 48 hours after dosing
MRTpo (mean residence time of tamsulosin HCl in the body after oral administration)	up to 48 hours after dosing
CL/F (apparent clearance of tamsulosin HCl in plasma after an extravascular administration)	up to 48 hours after dosing
Vz/F (apparent volume of distribution of tamsulosin HCl during the terminal phase λz following an extravascular administration)	up to 48 hours after dosing
RCmax,T/R (ratio of the Cmax value of the test treatment to the Cmax value of the reference treatment after single dose)	up to 48 hours after dosing
RAUC0-∞,T/R (ratio of the test treatment versus the reference treatment from zero to infinity, expressed as ratio of AUC values after single dose)	up to 48 hours after dosing
Number of subjects with adverse events	up to 21 days after last treatment
Assessment of tolerability by investigator on a 4-point scale	within 21 days after last treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 14, 2014
• First Submitted That Met QC Criteria: October 14, 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 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Paroxetine; Tamsulosin
• Other Study ID Numbers: 527.79