Fed Bioequivalence Study of CBZ Formulations

• ClinicalTrials.gov Identifier: NCT02132897
• Recruitment Status: Completed
• First Posted: May 7, 2014
• Last Update Posted: June 17, 2014
• Sponsor: Center for Clinical Pharmacology Research Bdbeq S.A.
• Information provided by (Responsible Party): Francisco E. Estevez-Carrizo, M.D., Center for Clinical Pharmacology Research Bdbeq S.A.

Tracking Information

• First Submitted Date: May 6, 2014
• First Posted Date: May 7, 2014
• Last Update Posted Date: June 17, 2014
• Study Start Date: May 2014
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2014)

• AUC0-240 [ Time Frame: 10 days ]
  Area Under the CBZ Concentration vs. time curve from sample time point 0 hour to sample time point 240 hour.
• AUC0-inf [ Time Frame: 0 to 240 hours ]
  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.
• Cmax [ Time Frame: 12 to 48 hours ]
  The maximum concentration in the CBZ concentrations vs. time curves for each subject and each formulation.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02132897 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 6, 2014)

AE [ Time Frame: 31 days ]

Recording of all adverse events (AE) occurring during the study: expected, unexpected and serious (SAE) from tree different sources. The AEs may be clinical occurrences, abnormal labs or ECG alterations.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 6, 2014)

• Tmax [ Time Frame: 12 to 48 hours ]
  Time from 0 concentration sample point to the Cmax sample point.
• Ke [ Time Frame: From 48 to 240 hours ]
  The constant rate of elimination (Ke) is the slope of the terminal phase of the CBZ concentration vs. time curve.
• T1/2e [ Time Frame: 48 to 240 hours ]
  It is the time that CBZ concentration, in the elimination (terminal) phase, fall off by half.
• Vital signs [ Time Frame: 20 days ]
  Measuring of blood pressure, heart rate, body temperature and ventilation rate.
• Admission and discharge screening [ Time Frame: 21 days ]
  Laboratory analysis and ECG performed prior to admission to the clinic and prior to discharge from the study.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Fed Bioequivalence Study of CBZ Formulations
• Official Title: Fed Bioequivalence Study of Carbamazepine Controlled Release Formulations in Healthy Male Uruguayan Subjects

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Investigator)

Condition

• Bio-equivalence Study
• Fed Conditions

Intervention

• Drug: Auration CR Tablets 400 Single Dose-Tegretol CR 400 Single Dose
  Carbamazepine CR Tablets 400 milligrams is given orally with 250 mL of water at room temperature.
  Other Names:

  • Carbamazepine
  • Carbamazepine CR
  • Carbamazepine CR 400 millligrams
• Drug: Tegretol CR 400 Single Dose-Auration CR 400 Single Dose
  Auration CR 400 milligrams Single Dose is given orally with 250 mL of water at room temperature.
  Other Names:

  • Carbamazepine
  • Carbamazepine CR
  • Carbamazepine CR 400

Study Arms

• TR (Test - Reference)
  Sequence : Auration CR 400 Single Dose/Tegretol CR 400 Single Dose
  Intervention: Drug: Auration CR Tablets 400 Single Dose-Tegretol CR 400 Single Dose
• RT (Reference - Test)
  Sequence: Tegretol CR 400 Single Dose/Auration CR 400 Single Dose
  Intervention: Drug: Tegretol CR 400 Single Dose-Auration CR 400 Single Dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2014): 20
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 2014
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Uruguay

Administrative Information

• NCT Number: NCT02132897
• Other Study ID Numbers: BDBEQ-CBZ400/EUFUY-023
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Francisco E. Estevez-Carrizo, M.D., Center for Clinical Pharmacology Research Bdbeq S.A.
• Study Sponsor: Center for Clinical Pharmacology Research Bdbeq S.A.
• Collaborators: Not Provided

Investigators

• Study Director: Francisco E. Estevez-Carrizo, M.D.; Center for Clinical Pharmacology Research Bdbeq S.A.
• Principal Investigator: Francisco T. Estevez-Parrillo, M.D.; Center for Clinical Pharmacology Research Bdbeq S.A.

• PRS Account: Center for Clinical Pharmacology Research Bdbeq S.A.
• Verification Date: June 2014