Clinical trial NCT01750931
Conditions: Arthritis, Rheumatoid
Keywords: BE study of Meloxicam GSK 15mg
Sponsor: GlaxoSmithKline
Start date: 2013-09-12; Completion date: 2013-10-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
It is a randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study of Meloxicam GSK 15 mg tablets manufactured by Savipharm J.S.Cc, Vietnam and Mobic® 15 mg tablets of Boehringer Ingelheim Pharma GmbH \& Co. KG Binger Str.173, 5521 Ingelheim am Rhein, Germany, in healthy, adult, human male subjects under fed condition. It is a pivotal study to demonstrate the bioequivalence of Meloxicam GSK 15 mg tablets manufactured by Savipharm J.S.C, Vietnam and Mobic® 15 mg tablets of Boehringer Ingelheim Pharma GmbH \& Co.KG Binger Str.173, 5521 Ingelheim am Rhein, Germany, in healthy adult human male subjects under fed condition.

This study will enroll 28 healthy adult human male subjects

Detailed description:
The objectives of this study are to:

To demonstrate the bioequivalence of Meloxicam GSK 15 mg tablets manufactured by Savipharm J.S.C, Vietnam and Mobic® 15 mg tablets of Boehringer Ingelheim Pharma GmbH \& Co.KG Binger Str.173, 5521 Ingelheim am Rhein, Germany, in healthy adult human male subjects under fed condition To monitor the safety of the study subjects. Study design: A randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study under fed condition. It is a pivotal study Sample size estimation: Based on the literature available \[Public assesment report Scientific Discussion Meloxicam "Arrow" Tablets 7.5 and 15 mg Meloxicam, DK/H/0905/001-002/MR\] sample size of 28 subjects will be enough to meet the study objective. And 28 healthy adult human male subjects will be enrolled.

Screening procedures:

Demographic data, medical and medication histories, complete physical examination, height, weight and BMI as well as 12 lead ECG, chest X-ray \[PA view\], vital signs \[blood pressure, pulse rate, respiratory rate and oral temperature\], hematology, biochemistry, HIV1\& 2, Hepatitis B and C, RPR test for Syphilis and urine analysis will be done at screening.

Urine drug screen, Liver chemistry test and Breath alcohol test to be done prior to each check-in.

Breath alcohol test to be done prior to each ambulatory visit blood collection. Housing: The study subjects will be housed at least 11 h prior to drug administration until after the 24 h blood sampling in each study period. The housing will be followed by three ambulatory visits \[48, 72 and 96 hr post dose\] during each period.

Study Meals Supervised fast for at least 10 h before dosing day breakfast will be maintained in each period. High calorie high fat breakfast will be served to subjects to start to consum 30 minutes before the scheduled dosing time. After dosing lunch, snacks and dinner will be served at 5, 8 and 12 h respectively. Meal plans will be identical for both the study periods.

Water will be permitted ad libitum except for 1 h before and until 1 h after post-dose.

Drug Administration:

As per the randomization schedule, one tablet of either test or reference product will be orally administered to each subject in each period in sitting posture, at 30 minutes after start of consuming served high calorie high fat breakfast on an overnight fast of at least 10 h. The investigational products will be administered with 240 ± 2 mL of water.

Subjects will be instructed not to chew or crush the tablet but should be swallowed. Compliance for dosing will be assessed by identification of subjects with subject ID card, identification of label on investigational product to confirm correct allocation of treatment and checking the oral cavity immediately after dosing.

Restrictions Subjects will remain in upright position \[sitting or ambulatory\] for two hours after dosing in each period except when clinically indicated to change the posture. The subjects will fast for at least 10 h prior to dosing day breakfast and 5 h post-dose. Water will be permitted ad libitum except for 1 h before and until 1 h after post dose.

Blood sampling:

In each period of the study, 26 blood samples of 6 mL each will be collected in K2EDTA vacutainers via an indwelling catheter placed in one of the forearm veins. Heparin-lock technique will be used to prevent clotting of blood in the indwelling catheter. Before each in-house blood sample is drawn through catheter, 0.5 mL of blood will be discarded so as to purge the heparin containing blood sample in the catheter. Blood can also be collected by direct venipuncture in case of cannula blockage, during ambulatory visits or for any other practical reasons. The two pre-dose blood samples will be collected within a period of 1 h before the drug administration. The post-dose blood samples will be collected at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 16.0, 24.0, 48.0, 72.0 and 96.0 h. The 48.0, 72.0 and 96.0 h post dose blood samples will be collected during ambulatory visits by direct venipuncture. Immediately after collection of blood, the sample will be kept in ice bath. After collecting the blood samples from all the subjects at each sampling time point, samples will be centrifuged at 4oC with 3500 rpm for 10 minutes. The plasma samples will be separated in duplicate and stored in pre-labeled polypropylene tubes at -70 ± 10°C or colder pending assay. The time interval between sample collection and the start of centrifugation should not exceed more than 45 minutes.

The total volume of blood drawn including the volume necessary for the laboratory tests, PK sample analysis and the volume of blood discarded before each in house blood draw will be about 360 mL per subject for the entire study.

Washout Period: Washout period will be of at least 14 days, but not exceeding 21 days between two dosing days.

Pharmacokinetic Parameter: Cmax, Tmax, AUC0-t, AUC0-∞, AUC%\_Extrap, Kel and t1/2 Analytical Methods: Meloxicam in plasma will be estimated using validated LC-MS/MS method.

Statistical Methods: Statistical analyses will be done using SAS® version 9.2 or higher. Analysis of variance \[ANOVA\] for log-transformed pharmacokinetic parameters \[Cmax, AUC0-t and AUC0-∞\] and two one-sided tests \[Schuirmann\] for bioequivalence will be performed. Power, ratio and 90% confidence interval for log-transformed pharmacokinetic parameters - Cmax, AUC0-t and AUC0-∞ will be calculated.

Standards for Bioequivalence: The calculated 90% Confidence Interval for the test to reference ratio of Meloxicam should fall within the range of 80%-125% for log transformed Cmax, AUC0-t and AUC0-∞ for the conclusion of bioequivalence.

Adverse Events The investigator or site staff is responsible for detecting, documenting and reporting events that meet the definition of an AE or SAE.

AEs will be collected from the start of Study Treatment and until the follow-up contact. Medical occurrences that begin prior to the start of study treatment but after obtaining informed consent may be recorded on the Medical History/Current Medical Conditions CRF.

SAEs will be collected over the same time period as stated above for AEs. However, any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication will be recorded from the time a subject consents to participate in the study up to and including any follow-up contact. All SAEs will be recorded and reported to the sponsor within 24 hours.

Investigators are not obligated to actively seek AEs or SAEs in former study participants. However, if the investigator learns of any SAE, including a death, at any time after a subject has been discharged from the study, and he considers the event reasonably related to the study treatment or study participation, the investigator would promptly notify the sponsor.

Arms: arm 1: A randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study under fed condition arm 2: A randomized, balanced, open label, crossover, two period, two treatment, two sequence, single dose, oral bioequivalence study under fed condition
Interventions: intervention 1: Meloxicam GSK 15mg intervention 2: Mobic 15mg
Intervention descriptions: intervention 1: To demonstrate the bioequivalence of Meloxicam 15 mg tablets manufactured by Savipharm J.S.C, Vietnam and Mobic® 15 mg tablets of Boehringer Ingelheim Pharma GmbH \&amp; Co.KG Binger Str.173, 5521 Ingelheim am Rhein, Germany, in healthy adult human male subjects under fed condition intervention 2: To demonstrate the bioequivalence of Meloxicam 15 mg tablets manufactured by Savipharm J.S.C, Vietnam and Mobic® 15 mg tablets of Boehringer Ingelheim Pharma GmbH \& Co.KG Binger Str.173, 5521 Ingelheim am Rhein, Germany, in healthy adult human male subjects under fed condition

Protocol documents: