Alfred E. Tiefenbacher (GmbH & Co. KG)

Background. The aim of this study was to demonstrate the equivalence of generic dorzolamide 2% eye drops solution versus the innovator formulation (Trusopt® eye drops solution) in patients with open-angle glaucoma or ocular hypertension. Methods. This prospective, monocentric, double-masked, active-controlled crossover phase III study included 32 patients. After washout, patients were randomized to reference product (Trusopt®) or test product (dorzolamide 2% eye drops, Rompharm Company SRL) for a 4-week period. Subsequent washout and crossover were performed. Drops were applied t.i.d. The primary efficacy endpoint was the difference in mean diurnal IOP. Goldmann applanation tonometry was performed at 8 am, 12 pm, and 4 pm at each visit, and safety was assessed by documentation of adverse events (AEs). Therapy adherence was documented by self-reporting and eye drop bottle weighing. An ANOVA with treatment, sequence, study period, and patient within the sequence as effects was performed and an additional post hoc ANCOVA including the baseline IOP was also performed. Results. 34 patients were randomized and analyzed in the safety population. The per-protocol population included 32 patients. According to the self-report, all patients were >80% compliant. Under the ANCOVA model, the 90% confidence interval for the average change of the IOP −0.27 mmHg (−1.17 mmHg–0.64 mmHg) is included by the acceptance range −1.5 mmHg to +1.5 mmHg after excluding 2 patients, which had falsely reported high therapy adherence. No clinically relevant difference was observed in frequency or severity of the AEs between both treatments. Conclusions. This study showed the equivalence of the tested generic dorzolamide 2% eye drops solution to the reference product Trusopt® eye drops solution. Trial Registration. This trial is registered with (ClinicalTrials.gov (identifier: NCT00878917) on April 9, 2009).

Vildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products (Galvus® and Eucreas®).

Three randomized studies with two-treatment, two-period, two-sequence crossover design were conducted in healthy adults. One study evaluated vildagliptin 50 mg tablets as single dose under fasting conditions. Vildagliptin-metformin FDC tablet strengths of 50/850 mg and 50/1000 mg were evaluated in separate studies as single dose under fed conditions, given 30 min after a standardized high-fat, high-calorie breakfast following 10 h overnight fasting. Blood samples for analysis were collected until 24 h after dosing in each study period. Bioequivalence between test (T) and reference (R) products required 90% confidence interval (CIs) for the geometric least square (LS) mean T/R ratio to be within 80-125% for the pharmacokinetic parameters, maximum plasma concentration (C_max), and area under the curve (AUC_0-t).

The 90% CIs of geometric LS means of T/R ratio for C_max and AUC_0-t with vildagliptin tablets of 50 mg were 92.22-103.94% and 99.00-102.66%, respectively; corresponding results with FDC tablets for 50/850 mg tablets were 94.81-115.41% and 95.28-106.00% for vildagliptin and 90.87-101.18% and 90.56-100.09% for metformin; for 50/1000 mg tablets C_max and AUC_0-t were 105.56-122.30% and 98.30-107.55%, respectively, for vildagliptin and 92.14-103.73% and 94.60-101.81%, respectively, for metformin. Other parameters such as AUC_0-∞, time to maximum concentration (T_max), and terminal half-life (t_1/2) were comparable between test and reference products. Adverse events (AEs), mainly vomiting, were reported without relevant difference between test and reference products in each study. AEs were generally mild and transient. No severe or serious AEs occurred.

The new generic drug products of vildagliptin and the FDCs of vildagliptin and metformin demonstrated bioequivalence to the approved originator products and are therefore expected to provide similar therapeutic effects.

The objective of this study was to determine the comparative pharmacoki-netics, safety and tolerability of test formulation Dasatinib tablets 140 mg with reference formulation Sprycel 140 mg filmtabletten after single dose administration under fasting conditions in 24 healthy adult male and female volunteers.This was an open label, two periods, two treatments, two-way crossover, controlled, block randomized, bioequivalence study in male and female, healthy volunteers, under fasting conditions.Each subject received a Dasatinib tablets 140 mg of test and reference product in each period re-spectively.Blood samples were collected before dosing and at various time points up to 24 h after drug administration.A total of 20 subjects re-ceived one dose of Dasatinib tablets 140 mg (TEST) or one dose of SPRYCEL 140 mg Filmtabletten (Reference) in two different occa-sions separated by a wash-out period of 16 days.Twenty eight (28) adverse events of mild and moderate intensity occurred in fourteen subjects in the study.These were not serious adverse events and the volunteers completely recovered before the end of the study.The statistical anal. of the phar-macokinetic data obtained in this study shows that the two Dasatinib formu-lations, Dasatinib tablets 140 mg of MSN Laboratories Pvt.Ltd., India - TEST and SPRYCEL 140 mg Filmtabletten, formulation of BRISTOL-MYERS SQUIBB PHARMA EEIG, United Kingdom - Reference are not bioequivalent, in fasting conditions.The Dasatinib Tablets 140 mg treatments (TEST and Reference), administered in single dose, orally, to male and female healthy volunteers, in fasting conditions were well tol-erated by all the subjects in this study.