Clinical trial NCT02132897: Fed Bioequivalence Study of CBZ Formulations
Official title: Fed Bioequivalence Study of Carbamazepine Controlled Release Formulations in Healthy Male Uruguayan Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bio-equivalence Study
Fed Conditions
Keywords: Antiepileptic
Carbamazepine
Bio-equivalence
Fed
Crossover
Lead sponsor: Center for Clinical Pharmacology Research Bdbeq S.A.
Sponsor class: OTHER
First posted: 2014-05-07
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Controlled release Carbamazepine (CBZ) is a antiepileptic, antineuralgic and mood stabilizer drug. The CR formulation of CBZ is slowly absorbed and the elimination half life varies with time due to metabolism autoinduction.

The primary objective of this study is to estimate the bioequivalence of the new brand generic product (Auration(R) CR) 400 mg manufactured in Uruguay vs. the innovative product (Tegretol(R) CR) 400 mg manufactured in Brasil, under fed conditions. The secondary objective will be evaluation of safety issues.

The study design will be randomized two sequences, two periods and crossover. For a power of not less than 80% sample size was estimated to be 20 healthy male subjects. Products will be administered with food (high calories/high fat breakfast) after an overnight fast.

Time vs. concentration curves will be built for each subject and formulation and Area Under Curve (AUC0240) will be estimated using the trapezoid rule, the AUC 0-inf. (from time 0 to infinity) will be estimated using the formula Cz/Ke, Cmax will be taken from the individual curves.

This parameters will be statistically processed with the WinNonlin 6.3 Pharmacokinetics/Statistic software in order to prove bioequivalence between the study products.


Eligibility criteria: Inclusion Criteria:

* Non-smoking or smokers of less than 5 cigarettes/day, within the age range of 18 to 50 years.
* Body Mass Index (BMI = weight/height2) greater than or equal to 18.5 kg/m2 and less than or equal to 24.9 kg/m2.
* No clinically significant findings in the physical examination, 12-lead electrocardiogram (ECG) and vital signs (blood pressure between 100-140/58-90 mmHg, heart rate between 50-99 beats/min, temperature between 35.8ºC and 37.6ºC, respiration rate between 12 and 20 breaths/minute)
* No clinical laboratory values outside of the acceptable range as per protocol, unless the Principal Investigator or Sub-investigator decides that they are not clinically significant (NCS).
* Availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements.
* The subject agrees to abstain from alcohol, coffee and other food and drinks containing methylxanthines (mate, tea, cola, chocolate) for 48hours, and grapefruit containing food and beverages for 72 hours prior study drug administration and during each study period.

Exclusion Criteria:

* Known history of hypersensitivity to Carbamazepine and/or related drugs.
* Positive test for hepatitis B surface antigen, hepatitis C or HIV.
* Known history of gastrointestinal (e.g: gastritis, inflammatory bowel disease, celiac disease), cardiac, pulmonary, endocrine, musculoskeletal, neurological, hematological, immunological, hepatic or renal disease, or malignancies, unless deemed NCS by the Principal Investigator or Sub-investigator.
* Any history of peptic ulcer disease or gastrointestinal (GI) bleeding.
* Any history of gastrointestinal surgery (except for appendectomy).
* Presence of any significant physical or organ abnormality.
* Any illness during the 4 weeks before this study, unless deemed NCS by the Clinical Investigator or Sub-investigator.
* Any history or evidence of psychiatric or psychological disease, unless deemed NCS by the Clinical Investigator or Sub-investigator.
* Any history of asthma (after 12 years of age).
* Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens).
* Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
* Any history of drug and psychoactive medicines abuse.
* Any recent history of alcohol abuse (less than 1 year).
* Use of any prescription medication within 14 days preceding this study.
* Use of vaccinations within 30 days preceding this study.
* Use of over-the-counter (OTC) medication within the 7 days preceding this study (except for spermicidal/barrier contraceptive products, sunscreen and sunblock products).
* Participation as a plasma donor in a plasmapheresis program within 7 days preceding this study.
* Blood donations within 60 days preceding and after this study.
* Participation in a clinical trial with an investigational drug within 180 days preceding this study, and agreement not to participate in a clinical trial for 180 days after this study.
* Intolerance to venipuncture.

Primary outcomes:
measure: AUC0-240
timeFrame: 10 days
measure: AUC0-inf
timeFrame: 0 to 240 hours
measure: Cmax
timeFrame: 12 to 48 hours
Secondary outcomes:
measure: AE
timeFrame: 31 days
Other outcomes:
measure: Tmax
timeFrame: 12 to 48 hours
measure: Ke
timeFrame: From 48 to 240 hours
measure: T1/2e
timeFrame: 48 to 240 hours
measure: Vital signs
timeFrame: 20 days
measure: Admission and discharge screening
timeFrame: 21 days
Locations:
city: Montevideo
country: Uruguay
facility: Center for Clinical Pharmacology Research Bdbeq S.A. Italian Hospital
Study officials:
affiliation: Center for Clinical Pharmacology Research Bdbeq S.A.
name: Francisco E. Estevez-Carrizo, M.D.
role: STUDY_DIRECTOR
affiliation: Center for Clinical Pharmacology Research Bdbeq S.A.
name: Francisco T. Estevez-Parrillo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: