Fasting Comparative Bioavailability of Two Tablet Formulations of Levodopa /Benserazide in Healthy Volunteers

Study Overview
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Brief Summary
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A group of 24 healthy volunteers receive one tablet of an association of levodopa 200 mg and benserazide 50 mg corresponding to two drug products: a test formulation (Evoser ®; Phoenix S.A.I.C. y F., Buenos Aires, Argentina) and a reference formulation (Madopar ®; Roche Pharma, Switzerland) to assess their relative bioavailability. After administration of each formulation 17 blood samples are taken and levodopa is measured by HPLC. Pharmacokinetic parameters (AUC, Tmax and Cmax) are compared.

Official Title
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Fasting Comparative Bioavailability of Two Tablet Formulations of Levodopa /Benserazide in Healthy Volunteers: A Single- Dose Randomized- Sequence, Open -Label Crossover Study

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Levodopa + benserazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Caucasian Argentinean males and females volunteers aged 21 to 50 years with a body mass index from 19 to 27 kg/m2 were enrolled in this study. All volunteers provided written informed consent prior to study initiation. Exclusion Criteria: History of cardiovascular, hepatic, renal, psychiatric, neurologic, hematologic, or metabolic disease Drug or alcohol abuse within 2 years before the start of the study Smoking HIV, hepatitis B, or hepatitis C infection Consumption of any prescribed or over-the-counter drug within 2 weeks before the study or Participation in a similar study within the past 6 months. Female subjects were not to be pregnant, planning to become pregnant, or breastfeeding at the time of the study, and were required to use an effective method of contraception (intrauterine device or hormonal method) throughout the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levodopa + benserazide (test formulation)<br>A randomized-sequence, open-label, 2-period crossover study assessing relative bioavailability of two drug products containing the association levodopa + benserazide. | Drug: Levodopa + benserazide<br>* Single oral dose of either Experimental or Active Comparator. Levodopa 200 mg/benserazide 50 mg tablets,with 200 mL of water.<br>|
| Active Comparator: Levodopa + benserazide (reference formulation)<br> | Drug: Levodopa + benserazide<br>* Single oral dose of either Experimental or Active Comparator. Levodopa 200 mg/benserazide 50 mg tablets,with 200 mL of water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Area Under the Curve and Peak Concentration of plasma levodopa reached after two different drug products containing levodopa + benserazide | In order to comply with Argentine regulation for marketing approval this study includes 24 healthy volunteers to investigate whether the relative bioavailability of the test formulation met the regulatory criterion for the assumption of bioequivalence to the branded formulation. After dosing with each formulation, 17 blood samples are taken to measure plasma levodopa concentration by HPLC. With plasma concentration values, pharmacokinetic parameters are calculated and bioequivalence assessed with WinNonLin software. | Blood samples are collected up to 6 hours after dosing. (day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety | Volunteers are asked about any discomfort or unusual manifestation they feel. Vital signs are recorded at each sampling time. | Clinical evaluation are performed up to 6 hours after dosing. (day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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levodopa, benserazide, bioequivalence, pharmacokinetics, A Single - Dose, Randomized- Sequence, Open -Label Crossover Study