Systemic Exposure of Catechins From Veregen 15% Ointment in Patients With External Anogenital Warts and From Oral Intake of Green Tea Beverage in Healthy Volunteers

Study Overview
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Brief Summary
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Investigation of systemic catechin exposure following topically administered Veregen® 15% ointment in patients with external genital and perianal warts and following oral intake of a standardized green tea beverage in healthy subjects. Pharmacokinetic parameters for the main catechin EGCg used as a marker of overall catechin exposure following dermal administration in the patient group will only be calculated if sufficiently consistent data can be obtained e.g. sufficient plasma catechin concentrations to pharmacokinetically evaluate plasma profiles for plasma catechin concentrations. If applicable, a safety margin for ointment use might need to be established with respect to intolerable systemic exposures of catechins following application of Veregen® ointment. In treatment arm 1, patients with anogenital warts will apply Veregen® 15% ointment 250 mg three times daily: in the morning, at midday, and in the evening on the defined anogenital administration area (total dose of 750 mg/d) for one week . In treatment arm 2, healthy subjects will ingest 500 mL commercially available green tea beverage (Lipton® Green Limone distributed by PepsiCo Deutschland GmbH, Neu-Isenburg, Germany), three times daily in the morning, at midday, and in the evening (total dose of 1500 mL/d) for one week. Plasma samples will be collected to aim for a complete pharmacokinetic assessment (over 24 hours) on Days 1 and 2 at Visit 2 and on Days 7 and 8 at Visit 3 (one week after first dosing). To avoid any influence on overall systemic catechin exposure deriving from any other source than Veregen® or Lipton Green Tea, all subjects participating in the trial (patients and healthy volunteers) will be asked to follow a defined diet abstaining from food or beverages known to containing catechins (a list of all prohibited and allowed foods and beverages will be provided to all subjects). For concomitant medication, only paracetamol and oral contraceptives are allowed.

Official Title
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An Open-label, Single-center Triqal to Evaluate Systemic Exposure of Catechins From Commercially Available, Topically Applied Veregen 15% Ointment in Patients With External Anogenital Warts and From Oral Intake of Green Tea Beverage in Healthy Volunteers

Conditions
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Anogenital Warts

Intervention / Treatment
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* Drug: Veregen
* Other: Green Tea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For both subject groups (treatment arms 1 + 2): Male and female subjects, 18 years of age or older at the time of enrollment. Subjects will be stratified by gender. Written informed consent. Ability to comply with the requirements of the study. For male patients and partners of male patients who are of child-bearing potential: use of two methods of effective contraception (oral contraceptives, hormone containing intrauterine device, depot injection, hormone implant or sterilization plus condom during the treatment period is mandatory. For women a negative pregnancy test and the willingness to use two methods of effective contraception (oral contraceptives, hormone containing intrauterine device, depot injection, hormone implant or sterilization plus condom during the treatment period is mandatory. For patients (treatment arm 1, additionally): Clinical diagnosis of external genital and perianal warts which can be located: in men: over the glans penis, foreskin, penis shaft, and scrotum; in women: on the vulva; in both gender: in the inguinal, perineal, and perianal areas For women a negative pregnancy test and willingness to abstain from cohabitation during the treatment phase. For male patients willingness to abstain from cohabitation during the treatment phase. Exclusion Criteria: For both subject groups (treatment arms 1 + 2): Participation in an investigational trial within 30 days prior to enrollment and for the whole study duration Any current uncontrolled infection Current known acute or chronic infection with Hepatitis virus B or C Known Human immunodeficiency virus infection Subjects with known history of instable diseases (diabetes, hypertension, etc.), severe gastritis or consuming diseases (cancer, multiple sclerosis, etc.), or liver or renal insufficiency. Any chronic or acute condition including the skin, susceptible, in the opinion of the investigator, of interfering with the evaluation of the drug effect Subject with any of the following: quantitative hematology values deviating more than 20% of upper or lower normal values clinical chemistry except electrolytes and liver enzymes deviating more than 50% of upper or lower normal values liver enzymes exceeding twice the upper limit of normal range (ULN) serum electrolytes deviating more than 20% of upper or lower normal values abnormal results in urine supported by clinical evidence laboratory values out of normal range and showing corresponding clinical signs or symptoms Systemic intake of virostatics within 30 days prior to enrollment and for the whole study duration, with the exception of acyclovir and the related drugs famcyclovir and valcyclovir Systemic intake of immunosuppressive or immunomodulatory medication or vaccination within 30 days prior to enrollment and for the whole study duration Organ allograft recipient Medication intake, including over the counter products and dietary supplements such as iodine, fluoride, or vitamins, which would interfere with study results, except paracetamol and oral contraceptives, within one week before and during the study course Subjects not willing to avoid the consumption of food or beverage containing catechins, e.g. green, black or Oolong tea, red wine For female patients: pregnancy or lactation Blood transfusion within 30 days prior to enrollment Subjects who are placed in an institution due to a judicial or official directive For patients (treatment arm 1; additionally) Previous participation in a trial investigating sinecatechins in the treatment of external genital and perianal warts Treatment of external genital warts within 14 days prior to enrollment and for the whole study duration Current infection with Herpes genitalis or history of Herpes genitalis infection within the last 3 months prior to enrollment Any current and/or recurrent pathologically relevant genital infections other than genital warts Known allergies against any of the ingredients of the ointment Internal (vaginal, urethral, or rectal) warts requiring treatment For healthy volunteers (treatment arm 2, additionally) Known hereditary fructose intolerance, glucose-galactose malabsorption or saccharase-isomaltase deficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Veregen<br>Veregen® (sinecatechins) Ointment, 15%, local application of 250 mg corresponding to 0.5 cm strand of ointment, 3 times daily (total dose of 750 mg/d) | Drug: Veregen<br>* Patients in treatment arm 1 will apply Veregen® 15% ointment (approved commercial source in US) in a total of 750 mg/day for one week, corresponding to application of maximal about 106,9 mg catechins/d, thereof maximal 81 mg ECGg per day). Patients will be instructed to apply fix portions of 250 mg three times daily on the defined anogenital administration area.<br>|
| Active Comparator: Tea<br>Lipton® Green Limone, a green tea beverage; oral intake of 500 mL green tea, 3 times daily (total dose on 1500 mL/d) | Other: Green Tea<br>* Healthy volunteers in treatment arm 2 will drink Lipton® Green Limone in a total of 1500 mL/d for one week, in portions of 500 mL three times daily after the meals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic exposure of green tea catechin EGC | The primary objective of this trial is to investigate the systemic exposure, and, if possible, the plasma concentrations and pharmacokinetics of green tea catechin EGCg after topically applied Veregen® 15% ointment in patients with external genital warts and that following oral intake of commercially available green tea beverage by healthy subjects. On the sampling Days 1/2 and 7/8, blood samples of 3 mL each will be collected (non-fasting condition) at specified time points (see above) | At time points 0, i.e. prior to the morning ingestion of 500 mL of commercial green tea beverage or the morning application of 250 mg Veregen® 15%, and 0.5, 1, 2, 4, 6, 8, 10, 12, 14, and 24 hours afterwards. |