Fasting Comparative Bioavailability of Two Tablet Formulations of Levodopa /Benserazide in Healthy Volunteers (PHOE10903)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Levodopa + benserazide

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Buenos Aires
• Collaborators: Laboratorios Phoenix S.A.I.C.y F.
• Investigators: Principal Investigator: Guillermo Di Girolamo, MD, PhD, Buenos Aires University

Publications and helpful links

General Publications

• Keller GA, Czerniuk P, Bertuola R, Spatz JG, Assefi AR, Di Girolamo G. Comparative bioavailability of 2 tablet formulations of levodopa/benserazide in healthy, fasting volunteers: a single-dose, randomized-sequence, open-label crossover study. Clin Ther. 2011 Apr;33(4):500-10. doi: 10.1016/j.clinthera.2011.04.012.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: March 31, 2011
• First Posted (Estimate): April 1, 2011

Study Record Updates

• Last Update Posted (Estimate): August 4, 2011
• Last Update Submitted That Met QC Criteria: August 3, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: pharmacokinetics; levodopa; bioequivalence; benserazide; A Single - Dose; Randomized- Sequence; Open -Label Crossover Study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa; Benserazide
• Other Study ID Numbers: Phoenix-Evoser (PHOE 1-0903)