Pharmacokinetic Study With Levodopa-carbidopa Fixed-dose Products in Healthy Subjects After Oral Administration

Study Overview
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Brief Summary
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The study is carried-out to describe and compare the plasma pharmacokinetics of levodopa and carbidopa after oral single-dose administration of 100 mg levodopa plus 25 mg carbidopa by means two fixed combination products (test: Isicom® 100/25 mg; reference: Nacom® 100/25 mg). Additionally, to describe and compare the safety and tolerability of the two investigational treatments administered to healthy subjects.

Detailed Description
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Isicom® 100/25 mg and Sinemet® (Trade name in Germany: Nacom®) 100/25 mg are authorised fixed-combination products containing 100 mg levodopa plus 25 mg carbidopa. These two formulations were tested for bioequivalence in 1997 (DESITIN trial № LCD-010/K); based on the regulatory provisions in place at that time (CPMP/EWP/QWP/1401/98), the two formulations could be accepted to be bioequivalent. The present study is proposed to be conducted in order to verify and confirm the bioequivalence of Isicom® 100/25 mg (test formulation) and Nacom® 100/25 mg (reference formulation) in agreement with the pertinent regulatory guidance that came in place 2010 (CHMP Guideline On The Investigation Of Bioequivalence - CPMP/EWP/QWP/1401/98- Rev. 1/ Corr - Jan.2010).

Official Title
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Open-label, Two-treatment, 4-period Replicated Crossover Study in Healthy Subjects to Investigate the Plasma Pharmacokinetics of Levodopa and Carbidopa After Oral Administration of Single Doses of Two Fixed-dose Combination Products

Conditions
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Fasted State

Intervention / Treatment
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* Drug: Levodopa Carbidopa immediate release tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females (females of non-childbearing potential or of childbearing potential while taking medically appropriate contraception) Race: Caucasian Age: 18 to 45 years Body weight: 50 100 kg Body Mass Index: 18 26 kg.m-2 Healthy based on the screening examination Willing and able to provide informed consent Exclusion Criteria: Previous participation in this trial or participant in any other trial during the last 90 days Donation of blood or plasma during the last 90 days or a history of blood loss exceeding 300 mL within the last 3 months History of any clinically relevant allergy including hypersensitivity to levodopa or carbi-dopa and related excipients Presence of any acute or chronic infection Presence or history of any relevant co-morbidity Resting systolic blood pressure > 160 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg Clinically relevant ECG-abnormalities, in particular prolonged QTc(F) of > 450 msec in males and > 460 msec in females Presence of any relevant abnormality in the laboratory safety tests, especially low haemo-globin (< 120 g/L in females and (< 136 g/L in males) and increased liver enzymes (2 times the upper limit of the normal range) Positive serology for HBsAg or anti HCV Positive HIV test Positive alcohol or urine drug test at screening Regular use of any prescription medicine (except for contraceptives) or over-the-counter product, herbal product, hormone supplement, etc. in the 30 days prior to the Screening visit History of alcohol and/or drug abuse and/or daily use of > 30 g alcohol Smoking more than 10 cigarettes/day or equivalent of other tobacco products Suspicion or evidence that the subject is not trustworthy and reliable Suspicion or evidence that the subject is not able to make a free consent or to understand the information in this regard. Positive pregnancy test Lactating Female subjects of child-bearing potential not using appropriate contraception in the 3 weeks prior to enrolment until two weeks after the last dose of the trial medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Active Comparator: Levodopa Carbidopa 100/25 tablets Test 1<br>single oral dose of levodopa carbidopa immediate release tablets | Drug: Levodopa Carbidopa immediate release tablets<br>* oral administration<br>* Other names: Nacom 100/25 mg;|
| Active Comparator: Levodopa Carbidopa 100/25 tablets Ref. 1<br>single oral dose of levodopa carbidopa immediate release tablets | Drug: Levodopa Carbidopa immediate release tablets<br>* oral administration<br>* Other names: Nacom 100/25 mg;|
| Active Comparator: Levodopa Carbidopa 100/25 tablets Test 2<br>single oral dose of levodopa carbidopa immediate release tablets | Drug: Levodopa Carbidopa immediate release tablets<br>* oral administration<br>* Other names: Nacom 100/25 mg;|
| Active Comparator: Levodopa Carbidopa 100/25 tablets Ref. 2<br>single oral dose of levodopa carbidopa immediate release tablets | Drug: Levodopa Carbidopa immediate release tablets<br>* oral administration<br>* Other names: Nacom 100/25 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax and AUC(0-tz) of levodopa and carbidopa | Cmax (maximal plasma concentration), AUC (area under the curve) | 12 hours |