Pharmacy & Therapeutics - October 2008 - (Page PP17)

PRODUCT PROFILER: Granisetron Transdermal Delivery System clinical practice, GTDS would be applied for a maximum of seven days. Taking this into account, the total number of AEs during Week 1 was only 265, again with headache and constipation the most common AEs. Other AEs reported that week (more than 1%) were abdominal pain (8.3%), nausea (4.53%), vertigo (2.26%), and hot flushes (1.41%).15 No other unexpected safety problems arose.15 Granisetron plasma concentrations were quantifiable eight hours after patch application in seven of the 24 patients who underwent pharmacokinetic evaluations. At 24 hours, all but one subject had measurable plasma granisetron concentrations; by 48 hours, all subjects had measurable plasma granisetron concentrations. Mean plasma granisetron concentrations reached plateaus of greater than 7 ng/mL for women and more than 2 ng/mL for men. The women (n = 12) had higher plasma granisetron concentrations (mean maximal values of 4.00 ng/mL) than the men (2.16 ng/mL). For the men, the Cavg was 1.51 ng/mL; for the women, it was 4.8 ng/mL. Concentrations decreased slowly until the patch was removed (at 168 hours). Mean Cavg values over the entire application were 1.31 for the men and 3.2 ng/mL for the women.15 From the study data, the investigator concluded that both the active granisetron patch and its matching placebo were slight irritants when applied on healthy skin. A smaller number of subjects wearing the active patch reported irritation compared with those wearing the placebo patch. A low sensitization potential (0.5%) was detected for the active granisetron patch, and no sensitization potential was detected for the placebo patch. Study 392MD/8/C: A Phase 2 Study Assessing the Safety, Efficacy, and Tolerability of the Granisetron Transdermal Delivery System in Comparison with Oral Granisetron in Chemotherapy-Induced Nausea and Vomiting Following a Single-Day Administration of Moderately Emetogenic Chemotherapy22 A double-blind, double-dummy, randomized, multicenter phase 2 study was conducted to compare the efficacy, safety, and tolerability of the granisetron patch and oral granisetron in CINV following a singleday administration of moderately emetogenic chemotherapy. This study was conducted in 21 centers in Germany in men and women with histologically and/or cytologically confirmed solid tumors. The patients ranged from 18 to 75 years of age and had not received any prior chemotherapy or chemotherapy in the previous six months; they were to receive a single-day chemotherapy regimen of moderately emetogenic potential (Table 10). The patients were randomly assigned, in a 1:1 ratio, to receive either GTDS or a placebo. The GTDS group received a 52-cm2 patch containing 34.3 mg of granisetron, followed by a placebo capsule. The comparator group received a placebo patch, followed by a 2-mg granisetron capsule.22 The appropriate patch was applied 24 hours before single-day administration of chemotherapy. Subjects received the appropriate capsule the next day, followed by chemotherapy one hour later. The patients were requested to keep the patch on for four days after chemotherapy. A final clinic visit was conducted four days after chemotherapy, and a telephone survey was conducted the following day. Throughout the study, patients were requested to record all symptoms of CINV (time, frequency and severity of nausea, retching, and vomiting) and the use of rescue medication in diary cards.22 A total of 210 patients (105 patients in each arm) were to be included in this study. After an interim analysis, conducted at the end of March 2005 in 133 patients who had been enrolled, recruitment was halted because the granisetron patch showed efficacy comparable to that of oral granisetron during the acute phase (0–24 hours); however, no superiority over oral granisetron was observed during the delayed phase (24–120 hours). At that time, 183 patients had been enrolled; 179 of these patients were randomly assigned (91 to the GTDS group, 88 to the comparator group).22 The investigators administered oral rescue medications (dexamethasone 8 mg, additional granisetron [Kevatril], and other antiemetic agents) to patients after chemotherapy if they needed it. Patients were required to record the time and dose of rescue medication in their diaries.22 CINV symptoms were documented in patient diaries as follows: 17

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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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