Pharmacokinetic Study With Levodopa-carbidopa Fixed-dose Products in Healthy Subjects After Oral Administration (LCD18K)

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

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.

Study Overview

• Status: Completed
• Conditions: Fasted State
• Intervention / Treatment: Drug: Levodopa Carbidopa immediate release tablets

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1527
    • Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Levodopa Carbidopa 100/25 tablets Test 1; single oral dose of levodopa carbidopa immediate release tablets	Drug: Levodopa Carbidopa immediate release tablets; oral administration; Other Names: isicom 100/25 mg; Nacom 100/25 mg
Active Comparator: Levodopa Carbidopa 100/25 tablets Ref. 1; single oral dose of levodopa carbidopa immediate release tablets	Drug: Levodopa Carbidopa immediate release tablets; oral administration; Other Names: isicom 100/25 mg; Nacom 100/25 mg
Active Comparator: Levodopa Carbidopa 100/25 tablets Test 2; single oral dose of levodopa carbidopa immediate release tablets	Drug: Levodopa Carbidopa immediate release tablets; oral administration; Other Names: isicom 100/25 mg; Nacom 100/25 mg
Active Comparator: Levodopa Carbidopa 100/25 tablets Ref. 2; single oral dose of levodopa carbidopa immediate release tablets	Drug: Levodopa Carbidopa immediate release tablets; oral administration; Other Names: isicom 100/25 mg; Nacom 100/25 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Desitin Arzneimittel GmbH

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 14, 2014
• First Posted (Estimate): April 17, 2014

Study Record Updates

• Last Update Posted (Estimate): April 17, 2014
• Last Update Submitted That Met QC Criteria: April 14, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination
• Other Study ID Numbers: LCD-018/K; 2013-003175-35 (EudraCT Number)