Influence of Pharmacogenetic Factors, Paroxetine and Clarithromycin on Pharmacokinetics of Clomiphene

Aim of the study is the clinical validation of the metabolism and the pharmakokinetic of Clomifen in correlation to CYP2D6 and inhibition of CYP3A4.

Study Overview

• Status: Completed
• Conditions: Anovulation; Cytochrome P450 CYP3A Enzyme Deficiency; Disorder Due Cytochrome P450 CYP2D6 Variant
• Intervention / Treatment: Drug: Clomiphene; Drug: clomiphene and paroxetine; Drug: clomiphene and clarithromycin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • BW
    • Stuttgart, BW, Germany, 70376
      • Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology and University of Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy
• Female caucasians
• Age 18 - 45 years old
• BMI 18.5 - 26 kg/m2

Exclusion Criteria:

• Persons with known sensitivity of Clomifen and/or Paroxetine and/or Clarithromycin
• Pregnancy/lactation period
• Meno-/postmenopausal
• Smokers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYP2D6 EM; clomiphene, clomiphene and paroxetine, clomiphene and clarithromycin	Drug: Clomiphene; clomiphene once 100 mg oral; Drug: clomiphene and paroxetine; clomiphene 100mg and paroxetine 3x40mg; Drug: clomiphene and clarithromycin; clomiphene 100mg and clarithromycin 9x500mg
Experimental: CYP2D6 IM; clomiphene, clomiphene and paroxetine, clomiphene and clarithromycin	Drug: Clomiphene; clomiphene once 100 mg oral; Drug: clomiphene and paroxetine; clomiphene 100mg and paroxetine 3x40mg; Drug: clomiphene and clarithromycin; clomiphene 100mg and clarithromycin 9x500mg
Experimental: CYP2D6 PM; clomiphene, clomiphene and paroxetine, clomiphene and clarithromycin	Drug: Clomiphene; clomiphene once 100 mg oral; Drug: clomiphene and paroxetine; clomiphene 100mg and paroxetine 3x40mg; Drug: clomiphene and clarithromycin; clomiphene 100mg and clarithromycin 9x500mg
Experimental: CYP2D6 UM; clomiphene, clomiphene and paroxetine, clomiphene and clarithromycin	Drug: Clomiphene; clomiphene once 100 mg oral; Drug: clomiphene and paroxetine; clomiphene 100mg and paroxetine 3x40mg; Drug: clomiphene and clarithromycin; clomiphene 100mg and clarithromycin 9x500mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC)of clomiphene	AUC of clomiphene and metabolites	1, 2, 4, 6, 8, 10, 12, 24, 72 and 168 hours after durg application
Peak Plasma Concentration (Cmax)of Clomiphene	Cmax of Clomiphene and metabolites	1, 2, 4, 6, 8, 10, 12, 24, 72 and 168 hours after drug application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of Clomiphene	Clearance of Clomiphene and metabolites	4, 8, 12 and 24 hours after drug application
Metabolomic	Metabolomic	4, 8, 12 and 24 hours after drug application
Tmax of clomiphene	Tmax of clomiphene and metabolites	4, 8, 12, 24 hours after drug application
Pharmacogenomics	Pharmacogenomics	once

Collaborators and Investigators

• Sponsor: Robert Bosch Gesellschaft für Medizinische Forschung mbH
• Investigators: Principal Investigator: Matthias Schwab, Prof., Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 2, 2011
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (Estimate): February 4, 2011

Study Record Updates

• Last Update Posted (Estimate): February 24, 2015
• Last Update Submitted That Met QC Criteria: February 23, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetic; clomiphene; CYP2D6 polymorphisms; inhibition of CYP2D6 and CYP3A4
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Anovulation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Protein Synthesis Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Paroxetine; Clarithromycin; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: IKP237; 2009-014531-20 (EudraCT Number)