Brain Neoplasms, Malignant, Primary Clinical Trial
Official title:
A Randomized, Open Label, Two-way Crossover, Single Dose Bioequivalence Study Comparing Dralitem® Capsules to the Reference Drug Temodal® Capsules in Patients With Primary Tumors of the Central Nervous System Under Fasting Conditions
The purpose of this crossover, single-dose, bioequivalence study is to compare the rate and extent of absorption of Temozolomide after the administration of the study product (Dralitem®, Monte Verde S.A.) and the reference product (Temodal®, Schering Plough) in primary Central Nervous System patients.
Prospective, randomized, two-period, two treatment, two-way crossover bioequivalence study
of two Temozolomide oral formulations (Dralitem vs. Temodal), in primary Central Nervous
System tumor patients under fasting conditions. Open label to the patients and investigators
and blind to the bioanalytical and clinical laboratories.
Study plan: days -21 to 0 (Recruitment period); days 1 to 5 (Treatment period); days 6 to 21
(Safety surveillance period). Sample size: 24 patients will be randomized. The patients will
be administered Temozolomide 200 mg/m2 on the first two days (Dralitem) of the treatment
cycle.
They will be admitted to the study clinical site on the evening of day 2. In the morning of
day 3 they will be randomized into two groups of equal size. According to the assigned
random number, each subject will receive a single oral dose of Temozolomide 200mg/m2 from
either Monte Verde Sociedad Anónima (SA) product (Dralitem) or from Schering-Plough product
(Temodal). The single dose of 200 mg/m2 will be reached with three different Temozolomide
capsule strengths: 20, 100 and 250 mg. Drugs will be administered with 200-240 ml of water
in semi-sitting upright position.
The following day (day 4) each subject will receive an oral dose of Temozolomide 200 mg/m2
of the product that did not receive the day before. On days 3 and 4 after drug
administration, blood samples will be obtained for pharmacokinetic evaluation. The patient
will be discharged from the clinical site on day 4 after completion of sampling for
pharmacokinetic analysis. On day 5, all patients will receive Temozolomide 200 mg/m2
(Dralitem).
On days 3 and 4, samples of venous blood will be withdrawn from the forearm vein of each
volunteer at the following time points: 0 (pre-dose) and 0.25, 0.5, 0.75, 1.0, 1.25, 1.5,
1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours post-dose after each period administration.
The washout period between the treatment arms was 10 hours, on days 3 and 4. Samples will be
processed according to the validated method MANA (Método Analítico) - PLB (Proyecto
Laboratorio Bioanalítico) 004 - TEM (Temozolomide) - 01/01. Measurement of plasma
concentration of Temozolomide was performed using High Performance Liquid Chromatography
(HPLC) followed by detection by tandem mass spectrometry (MS / MS).
The area under the curve (AUC) and the Cmax levels of the drug vs. time will be obtained for
each subject. The resulting values of the logarithmic transformation of these parameters
will be used for statistical comparisons (mixed effects ANOVA). The limits of the 90%
confidence interval for the ratio of log transformed pharmacokinetic parameters will be
calculated. Bioequivalence criteria: each calculated confidence interval should be within
the acceptance range from 80.00 to 125.00.
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Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment