Drug-Drug Interaction of Clomipramine HCl and Sildenafil Citrate in Healthy Males

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and pharmacokinetics/pharmacodynamics of co-administration of Clomipramine HCl 15mg and Sildenafil citrate 100mg compared to the effects after single oral administration in Korean healthy male volunteers.

Detailed Description
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Clomipramine is a dibenzazepine-derivative tricyclic antidepressant (TCA) and is a potent inhibitor of serotonin and norepinephrine reuptake. Clomipramine may be used in a variety of indications. Condencia Tab contains low dose of 15mg of clomipramine HCl as an active ingredient, which is newly approved to market for the treatment of premature ejaculation. This study is a prospective, randomised, open-labeled, 6-sequence, 3-period, 3-treatment, crossover, and single-center clinical trial. A total of 30 healthy male volunteers will be enrolled and randomised into one among 6 groups (5 subjects per a group). The safety and PK/PD characteristics of co-administration of Clomipramine HCl and Sildenafil citrate will be investigated closely compared to the effects after single dose administrations.

Official Title
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A Randomized, Open-labeled, 6-sequence, 3-period, 3-treatment Crossover Study to Evaluate the Effect of Co-administration of Clomipramine HCl (Condencia Tab.) 15mg and Sildenafil Citrate (Viagra Tab.) 100mg on the Safety and Pharmacokinetic/Pharmacodynamic Properties of Clomipramine and Sildenafil Compared to the Effects After Single Oral Administration in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Treatment 1
* Drug: Treatment 2
* Drug: Treatment 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Korean healthy males aged between 19 and 65 Body weight between 60kg and 90kg, BMI between 19 and 27 Given informed consent Exclusion Criteria: Clinically significant medical history and/or concurrent disease SBP >=140 mmHg or <=90 mmHg, DBP >=95 mmHg or <=50 mmHg Orthostatic hypotension Hypersensitivity to any ingredient of investigational drugs Severe bleeding or blood donation within 8 weeks prior to study participation Alcoholism or drug abuser Smoking more than 0.5 pack-year Persistent alcohol consumption more than 21 units(210g)/week Participation in other investigational clinical trial

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A<br>Treatment 1 - Treatment 2 - Treatment 3 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|
| Experimental: Sequence B<br>Treatment 1 - Treatment 3 - Treatment 2 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|
| Experimental: Sequence C<br>Treatment 2 - Treatment 1 - Treatment 3 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|
| Experimental: Sequence D<br>Treatment 2 - Treatment 3 - Treatment 1 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|
| Experimental: Sequence E<br>Treatment 3 - Treatment 1 - Treatment 2 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|
| Experimental: Sequence F<br>Treatment 3 - Treatment 2 - Treatment 1 | Drug: Treatment 1<br>* An oral single dose administration<br>* Other names: Clomipramine HCl 15mg (Condencia Tab);Drug: Treatment 2<br>* An oral single dose administration<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);Drug: Treatment 3<br>* Co-administration of oral single doses<br>* Other names: Sildenafil citrate 100mg (Viagra Tab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The systemic exposure measured as area under the curve (AUC) |  | From Day 1(dosing) to Day 4(72hrs) | 
| The maximum concentration (Cmax) |  | From Day 1(dosing) to Day 4(72hrs) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters except the primary endpoints | Including Tmax, T1/2, AUCnorm, Cmax norm, CL/f and Cmax/AUC | From Day 1(dosng) to Day 4(72hrs) | 
| The maximum change of systolic blood pressures within 12hrs after dosing | At supine and upright positions | Day 1(dosing) to Day 2(12hrs) | 
| Adverse events |  | For 3 Weeks after dosing | 
| The maximum change of dystolic blood pressure within 12hrs after dosing | at supine and upright positions | From Day 1(dosing) to Day 2(12hrs) | 
| The maximum change of heart rates within 12 hours after dosing | At supine and upright positions | From Day 1(dosing) to Day 2(12hrs) | 
| The rate of the subjects who experienced the clinically significant change of blood pressures | Clinically significant changes will be classified into 4 groups: SBP change >=30 or 20 mmHg, DBP change >= 20 or 10 mmHg (at supine and upright positions) | From Day 1(dosing) to Days 2(12hrs) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clomipramine, Premature ejaculation