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

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

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

Conditions
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Anovulation, Disorder Due Cytochrome P450 CYP2D6 Variant, Cytochrome P450 CYP3A Enzyme Deficiency

Intervention / Treatment
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* Drug: Clomiphene
* Drug: clomiphene and paroxetine
* Drug: clomiphene and clarithromycin


Participation Criteria
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Eligibility Criteria
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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

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

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, clomiphene, CYP2D6 polymorphisms, inhibition of CYP2D6 and CYP3A4