Clinical trial NCT02116465: Pharmacokinetic Study With Levodopa-carbidopa Fixed-dose Products in Healthy Subjects After Oral Administration
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fasted State
Lead sponsor: Desitin Arzneimittel GmbH
Sponsor class: INDUSTRY
First posted: 2014-04-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Cmax and AUC(0-tz) of levodopa and carbidopa
timeFrame: 12 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Department of Clinical Pharmacology
Study officials:
References: