S F Gordon1. 1. Future HealthCare Research Centers, Atlanta, GA 30340, USA.
Abstract
OBJECTIVE: To describe the efficacy, safety, and wearability of estrogen replacement therapy of a 7-day estradiol transdermal system (Climara), developed using new drug-in-adhesive technology. STUDY DESIGN: The pharmacokinetics of the 7-day system were investigated in single- and multiple-dose studies, a relative bioavailability study of the two patch sizes, and comparative studies with the twice-weekly transdermal system (Estraderm). Safety and efficacy in the treatment of vasomotor symptoms compared with conjugated equine estrogens (Premarin) and placebo were evaluated in two 11-week, randomized, double-blind, multicenter trials in 603 women; the data are combined in this report. Irritation and adhesion were also evaluated in comparative studies with Estraderm, Micropore (an inert once-weekly tape), and placebo controls. RESULTS:Blood levels were sustained for the full 7 days of patch wear, there was no drug accumulation, and a physiologic estrone to estradiol ratio was maintained. Pharmacokinetics studies showed dose proportionality of the 0.05 and 0.1 mg/day patches. Both patch sizes significantly decreased the frequency of hot flushes compared with placebo and were comparable with conjugated equine estrogens. There was a statistically significant difference between the two patch sizes. The mean overall decline in the hot flush rate was 74.6% for the 0.1 mg patch versus 64.5% for the 0.05 mg patch (p < or = 0.05). The combined data also showed that the onset of efficacy is within 1 to 2 weeks after the start of therapy and that efficacy is fully sustained during the 7-day patch wear period with some diminution of effect during the treatment-free week of each cycle. Treatment was well tolerated. Adverse events led to withdrawal from the studies in 8.9% of subjects. In most of these (6.8% of subjects), the cause was adverse skin reactions. Skin irritation was similar to Estraderm in comparative studies, whereas adhesion was significantly better with Climara. CONCLUSION: The Climara patch delivers estradiol for a full 7 days. Clinical efficacy of both patch sizes is comparable with currently accepted therapy and is sustained for the entire week of patch wear. A significant difference in response between the two doses supports dose titration. The patch is well tolerated and has excellent adhesion.
RCT Entities:
OBJECTIVE: To describe the efficacy, safety, and wearability of estrogen replacement therapy of a 7-day estradiol transdermal system (Climara), developed using new drug-in-adhesive technology. STUDY DESIGN: The pharmacokinetics of the 7-day system were investigated in single- and multiple-dose studies, a relative bioavailability study of the two patch sizes, and comparative studies with the twice-weekly transdermal system (Estraderm). Safety and efficacy in the treatment of vasomotor symptoms compared with conjugated equine estrogens (Premarin) and placebo were evaluated in two 11-week, randomized, double-blind, multicenter trials in 603 women; the data are combined in this report. Irritation and adhesion were also evaluated in comparative studies with Estraderm, Micropore (an inert once-weekly tape), and placebo controls. RESULTS: Blood levels were sustained for the full 7 days of patch wear, there was no drug accumulation, and a physiologic estrone to estradiol ratio was maintained. Pharmacokinetics studies showed dose proportionality of the 0.05 and 0.1 mg/day patches. Both patch sizes significantly decreased the frequency of hot flushes compared with placebo and were comparable with conjugated equine estrogens. There was a statistically significant difference between the two patch sizes. The mean overall decline in the hot flush rate was 74.6% for the 0.1 mg patch versus 64.5% for the 0.05 mg patch (p < or = 0.05). The combined data also showed that the onset of efficacy is within 1 to 2 weeks after the start of therapy and that efficacy is fully sustained during the 7-day patch wear period with some diminution of effect during the treatment-free week of each cycle. Treatment was well tolerated. Adverse events led to withdrawal from the studies in 8.9% of subjects. In most of these (6.8% of subjects), the cause was adverse skin reactions. Skin irritation was similar to Estraderm in comparative studies, whereas adhesion was significantly better with Climara. CONCLUSION: The Climara patch delivers estradiol for a full 7 days. Clinical efficacy of both patch sizes is comparable with currently accepted therapy and is sustained for the entire week of patch wear. A significant difference in response between the two doses supports dose titration. The patch is well tolerated and has excellent adhesion.
Authors: Margaret A Zimmerman; Benard O Ogola; Mary M Wilkinson; Bruna Visniauskas; Carmen De Miguel; Jill M Daniel; Sarah H Lindsey Journal: Menopause Date: 2020-12 Impact factor: 3.310