Pharmacy & Therapeutics - October 2008 - (Page PP10)

PRODUCT PROFILER: Granisetron Transdermal Delivery System Clinical Trials Five studies have been conducted to evaluate the efficacy and safety of the granisetron transdermal delivery system (GTDS): three phase 1 trials, one phase 2 trial, and one phase 3 trial. was considered as hour zero (0). Patients were observed throughout the study at predetermined time points, up to and including Day 7.21 Patient assessments included a physical examination, routine laboratory evaluations, vitals signs, AEs, a 12-lead electrocardiogram (ECG), dermal tolerability, and patch adhesiveness.21 All 12 subjects completed the study. Pharmaco kinetic parameters could not be analyzed for one subject, because none of the samples could be quantified analytically for their content of granisetron.21 Therefore, all pharmacokinetic parameters from this trial were based on data obtained from 11 subjects. Nine subjects showed quantifiable levels of granisetron after wearing the patch for 24 hours. In the remaining subjects, plasma concentrations exceeded the lower limit of quantification (0.1 ng/mL) within 48 hours of patch application. The maximum plasma concentration (Cmax) obtained in any subject was 5.2 ng/mL. The geometric mean of the maximum values was 1.5 ng/mL (geometric coefficient of variation [CV] of 72%) with a median peak time of concentration (tmax) of 48 hours. Steady-state concentrations were reached in 24 to 30 hours after patch application.21 Data from Figure 3 demonstrate sustained delivery over a five-day period.21 The area-under-the-curve (AUC) concentration time from time 0 to 132 hours was estimated at 114 hours • ng/mL (geometric CV of 88%). The inter-individual vari- Study 392MD/4/C: A Phase 1 Pharmacokinetics/ Safety/Patch Adhesiveness Study21 A single-center, single-dose bioavailability phase 1 study was conducted to confirm the systemic bioavailability of GTDS, to determine the resultant pharmacokinetic profile, to assess the dermal irritation potential of GTDS, and to evaluate patch adhesiveness.21 This study was conducted in Germany from June to July 2003 in 12 healthy subjects over a period of five days.21 The primary objective was to confirm the systemic bioavailability of granisetron from a transdermal patch. Secondary objectives were to assess the pharmacokinetic profile of granisetron delivered from a transdermal patch and to compare the dermal irritation potential of this patch with that of a placebo transdermal patch. The objective of assessing the product’s adhesiveness was to compare the gran isetron and placebo patches. The safety objective was to assess the local and systemic safety of the granisetron patch.21 Criteria required enrollees to be healthy smoking and nonsmoking Caucasian men and women between 18 and 40 years of age. Six healthy males and six healthy females were enrolled.21 No other drugs were permitted for 14 days before the study began except contraceptives for women,21 and no 3.0 prescription or nonprescription drugs (except contraceptives in women) were allowed during the study period. Drugs could be used 2.5 only when necessary to treat an adverse event (AE) after a consultation with the study inves2.0 tigator.21 Two granisetron transdermal patches (each 1.5 15 cm 2) were applied concurrently to the upper abdomen of all patients on Day 1 and 1.0 remained on the skin continuously for five days.21 A placebo patch was applied to the 0.5 left side of the abdomen, and a 9.9-mg granisetron patch was applied to the right side of 0.0 the abdomen.21 The patch contained a gran0 6 12 18 24 30 36 48 60 72 84 96 108 120 isetron dose of 660 mcg/cm2, and with the Study time (hr) total area of 15 cm2, the maximum drug expoFigure 3 Mean concentrations of granisetron. (From Study sure was 9.9 mg over a period of five days.21 392MD/4/C, p 38.)21 The patches were removed at the 120th hour on Day 6; the time of patch application ng/mL 126 132 10

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - October 2008

Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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