Fed Bioequivalence Study of CBZ Formulations

NCT02132897 | Completed Phase 1 DMC

• 1 other identifier: BDBEQ-CBZ400/EUFUY-023
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Bio-equivalence Study; Fed Conditions

Keywords

Antiepileptic; Carbamazepine; Bio-equivalence; Fed; Crossover

Outcome Measures

Primary Outcomes (3)

• AUC0-240

  Area Under the CBZ Concentration vs. time curve from sample time point 0 hour to sample time point 240 hour.

  10 days

• AUC0-inf

  Area Under the CBZ Concentrations vs, time curve from sample time point 0 hour to sample time point 240 hours plus extrapolation to infinity of the terminal concentration slope.

  0 to 240 hours

• Cmax

  The maximum concentration in the CBZ concentrations vs. time curves for each subject and each formulation.

  12 to 48 hours

Secondary Outcomes (1)

• AE

  31 days

Other Outcomes (5)

• Tmax

  12 to 48 hours

• Ke

  From 48 to 240 hours

• T1/2e

  48 to 240 hours

Study Arms (2)

TR (Test - Reference)

OTHER

Sequence : Auration CR 400 Single Dose/Tegretol CR 400 Single Dose

Drug: Auration CR Tablets 400 Single Dose-Tegretol CR 400 Single Dose

RT (Reference - Test)

OTHER

Sequence: Tegretol CR 400 Single Dose/Auration CR 400 Single Dose

Drug: Tegretol CR 400 Single Dose-Auration CR 400 Single Dose

Interventions

Auration CR Tablets 400 Single Dose-Tegretol CR 400 Single Dose DRUG

Carbamazepine CR Tablets 400 milligrams is given orally with 250 mL of water at room temperature.

Also known as: Carbamazepine, Carbamazepine CR, Carbamazepine CR 400 millligrams

TR (Test - Reference)

Tegretol CR 400 Single Dose-Auration CR 400 Single Dose DRUG

Auration CR 400 milligrams Single Dose is given orally with 250 mL of water at room temperature.

Also known as: Carbamazepine, Carbamazepine CR, Carbamazepine CR 400

RT (Reference - Test)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Center for Clinical Pharmacology Research Bdbeq S.A.: lead

Study Sites (1)

Center for Clinical Pharmacology Research Bdbeq S.A. Italian Hospital

Montevideo, Montevideo Department, 11800, Uruguay

Location

MeSH Terms

Conditions

Lecithin Cholesterol Acyltransferase Deficiency

Interventions

Carbamazepine

Condition Hierarchy (Ancestors)

Hypoalphalipoproteinemias; Hypolipoproteinemias; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Francisco E. Estevez-Carrizo, M.D.

  Center for Clinical Pharmacology Research Bdbeq S.A.

  STUDY DIRECTOR

• Francisco T. Estevez-Parrillo, M.D.

  Center for Clinical Pharmacology Research Bdbeq S.A.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Medical Officer

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 7, 2014
• Study Start: May 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 17, 2014

Record last verified: 2014-06

Locations

UR (1)