Alan C. Fisher

Contraceptive efficacy and cycle control with the Ortho Evra™/Evra™ transdermal system: the analysis of pooled data

OBJECTIVE To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra). DESIGN Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. SETTING 183 centers. PATIENT(S) 3,319 women. INTERVENTION(S) Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S) Contraceptive efficacy and cycle control. RESULT(S) Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. CONCLUSION(S) In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Topiramate for the Treatment of Binge Eating Disorder Associated With Obesity: A Placebo-Controlled Study

BACKGROUND In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial. METHODS Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized. RESULTS A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate. CONCLUSIONS This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.

Topiramate for Migraine Prevention in Children: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective.—To assess the efficacy and safety of topiramate for the prevention of pediatric migraine with or without aura in a double‐blind, randomized, placebo‐controlled trial.

Efficacy and safety of a transdermal contraceptive system

OBJECTIVES To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 μg and ethinyl estradiol 20 μg daily. METHODS In this open‐label, 73‐center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7‐day patches (21 days) followed by 1 patch‐free week. RESULTS The overall and method‐failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7‐day drug‐free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild‐to‐moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

Assessment of compliance with a weekly contraceptive patch (Ortho Evra/Evra) among North American women

OBJECTIVE To determine compliance with the contraceptive patch (Ortho Evra/Evra) overall and by age among women in North America and to compare rates of perfect use with those of an established oral contraceptive. DESIGN Data were pooled for three contraceptive studies in which women participated for up to 13 cycles; the subset of centers in North America was used in this analysis. SETTING 76 North American centers. PATIENT(S) Healthy women 18-45 years of age. INTERVENTION(S) In all studies, the patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S) Perfect use for the patch or oral contraceptive, defined as 21 consecutive days of drug-taking followed by a 7-day drug-free period; for contraceptive patch users, no patch could be worn for more than 7 days. Oral contraceptives were used according to package labeling. RESULTS For all contraceptive patch users in North America (n = 1,785), perfect use was consistent across age groups. The percentage of cycles with perfect use of the patch ranged within age groups from 88.1% to 91.0%. In the comparative study conducted only in North America, perfect use was also consistent across age groups for the patch (n = 812), but rates of perfect use for the oral contraceptive (n = 605) differed significantly by age. CONCLUSION(S) Age did not affect compliance with the patch among all North American women studied. In a comparative study of women at North American centers, compliance with the weekly contraceptive patch was significantly better than with an established oral contraceptive. The contraceptive patch is uniformly easy to use across all ages.

Ortho Evra™/Evra™ versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error

OBJECTIVE To compare the effects of the contraceptive patch to oral contraceptives (OCs) on follicular size and incidence of ovulation in normal cycles and after dosing errors. DESIGN Randomized, open-label. SETTING Twelve centers. PATIENT(S) One hundred twenty-four ovulatory women. INTERVENTION(S) Subjects received either the patch (groups 1 and 2) or one of three OCs. Correct dosing occurred in cycles 1, 2, 3, and 5. The following dosing errors were planned during cycle 4, a shortened 10-day cycle: [1] patch group 1 subjects wore one patch for 10 consecutive days; [2] for patch group 2 and OC subjects, 7 dosing days were followed by 3 drug-free days. MAIN OUTCOME MEASURE(S) Follicular size, as determined at each cycle by the maximum mean follicular diameter. RESULT(S) After a 3-day dosing error, follicular size was significantly smaller in the patch group (mean, 7.0 mm) vs. each OC group (range of means, 11.8-17.1 mm). Similar results were seen after proper dosing. The incidence of ovulation was significantly lower for the patch users than for women using OCs. CONCLUSION(S) Follicular size and incidence of ovulation were significantly reduced among contraceptive patch users compared with women using OCs in normal cycles and after planned dosing errors.

Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.

OBJECTIVE: To compare bleeding profiles and satisfaction among women using a norelgestromin/ethinyl estradiol (E2) transdermal contraceptive patch in an extended regimen to those among women using a traditional 28-day patch regimen. METHODS: Healthy, regularly menstruating women (N = 239) were randomly assigned (2:1 ratio) to receive the norelgestromin/ethinyl E2 transdermal patch in an extended regimen (weekly application for 12 consecutive weeks, 1 patch-free week, and 3 more consecutive weekly applications, n = 158) or a cyclic regimen (4 consecutive cycles of 3 weekly applications and 1 patch-free week, n = 81). Subjects recorded bleeding data daily and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of the norelgestromin/ethinyl E2 transdermal patch resulted in fewer median bleeding days (6 compared with 14, P < .001), bleeding episodes (1 compared with 3, P < .001), and bleeding or spotting episodes (2 compared with 3, P < .001) compared with cyclic use during days 1–84; median numbers of bleeding or spotting days were similar between regimens (14 compared with 16, P = .407) during this time. Extended use delayed median time to first bleeding to 54 days compared with 25 days with cyclic (P < .001). Subjects were highly satisfied with both regimens. Although not statistically significant, slightly more adverse events were reported with the extended than with the 28-day regimen. CONCLUSION: Compared with cyclic use, extended use of the norelgestromin/ethinyl E2 transdermal patch delayed menses and resulted in fewer bleeding days. This regimen may represent a useful alternative for women who prefer fewer episodes of withdrawal bleeding. LEVEL OF EVIDENCE: I

A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra™/Evra™)

OBJECTIVE To review the safety and tolerability of the contraceptive patch (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present the pooled safety and tolerability of the patch across three pivotal studies. DESIGN Three open-label, contraceptive studies of up to 13 treatment cycles. SETTING 183 centers. PATIENT(S) Comparative study (812 patch, 605 oral contraceptive); pooled analysis (3,330 patch). INTERVENTION(S) The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive was dosed according to the U.S. physician package insert. MAIN OUTCOME MEASURE(S) Adverse events, laboratory tests, vital signs, and body weight. RESULT(S) The incidence of most events was similar between the patch and oral contraceptive groups, with the exception of a higher incidence of application site reactions, breast discomfort (cycles 1 and 2 only), and dysmenorrhea in the patch group. Pooled analysis demonstrated that most application site reactions (92%) and breast symptoms (86%) were mild or moderate in severity, and <2% of participants discontinued the patch because of either event. Only 7 (0.2%) participants experienced a serious adverse event classified as possibly, probably, or likely related to the patch. The mean change in body weight from baseline to the end of treatment was an increase of 0.3 kg. CONCLUSION(S) Overall, the contraceptive patch is well tolerated and has a side effect profile similar to an established oral contraceptive.

A double-blind placebo-controlled comparison of tramadol/acetaminophen and tramadol in patients with postoperative dental pain.

&NA; The objective of this study was to compare the analgesic efficacy of tramadol/acetaminophen (APAP) (total dose 75 mg/650 mg) and tramadol (total dose 100 mg) for the control of pain after oral surgery. A total of 456 patients with moderate‐to‐severe pain within 5 h after extraction of two or more third molars were randomized to receive two identical encapsulated tablets containing tramadol/APAP 37.5 mg/325 mg, tramadol 50 mg, or placebo. Tramadol/APAP was superior to tramadol (P<0.001) or placebo (P<0.001) on all efficacy measures: total pain relief (PAR) over 6 h (7.4, 2.5, and 1.5, respectively, on a scale of 0–24); sum of pain intensity differences (PIDs) (3.1, 0.6, and 0.1, respectively, on a scale of −6 to 18); and sum of PAR and PID (10.5, 3.1, and 1.6, respectively, on a scale of −6 to 42). Median times to onset of perceptible and meaningful PAR were 37.6 and 126.5 min, respectively, for the tramadol/APAP group (P<0.001 for each, compared with tramadol and placebo arms). The most common adverse events with active treatment were nausea, dizziness, and vomiting; these events occurred more frequently in the tramadol group than in the tramadol/APAP group. This study established the superiority of tramadol/APAP 75 mg/650 mg over tramadol 100 mg in the treatment of acute pain following oral surgery.

Integrated summary of ORTHO EVRA™/EVRA™ contraceptive patch adhesion in varied climates and conditions.

OBJECTIVE To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra). DESIGN Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study. SETTING 184 centers. PATIENT(S) 3,349 healthy women. INTERVENTION(S) In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center. MAIN OUTCOME MEASURE(S) Patch adhesion. RESULT(S) In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study. CONCLUSION(S) The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.