Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

OBJECTIVES: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 µg ethinylestradiol [EE] and 120 µg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 µg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years. METHODS: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study. RESULTS: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result. CONCLUSIONS: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

Safety and efficacy of the NuvaRing® Applicator in healthy females: a multicenter, open-label, randomized, 2-period crossover study.

INTRODUCTION: We assessed performance and safety of the NuvaRing® Applicator. METHODS: We randomized women (18-45 years) to insert a placebo ring using the applicator or fingers-only and then vice versa. We assessed outcomes post-insertion and then 24-72 h later. RESULTS: Insertion was 100% successful using both methods (applicator, n=163; fingers-only, n=162). A total of 8.6% (applicator) and 4.3% (fingers-only) of subjects reported at least 1 treatment-related adverse event (AE); all were mild. Subjects reported 5 applicator-related AEs (vulvovaginal pain, 4; abdominal cramping, 1). There was no vaginal bleeding within 15 h post-applicator use. Ring expulsions were rare (applicator, 1; fingers-only, 2). CONCLUSION: NuvaRing Applicator is effective and well-tolerated (NCT02275546).

Upper gastrointestinal tolerability of alendronate sodium monohydrate 10 mg once daily in postmenopausal women: a 12-week, randomized, double-blind, placebo-controlled, exploratory study.

BACKGROUND: The dissolution profiles of generic oral bisphosphonate alendronate (ALN) sodium for the treatment of postmenopausal osteoporosis differ by formulation, suggesting potential differences in the risk for upper gastrointestinal (GI) irritation. OBJECTIVE: This study compared the tolerability profile of ALN monohydrate with that of placebo, with a focus on upper GI irritation, in postmenopausal women with osteoporosis. METHODS: This multicenter, double-blind, placebo-controlled estimation study enrolled postmenopausal women with osteoporosis. Patients were randomized in a 2:1 ratio to receive ALN monohydrate 10 mg or placebo once daily for 12 weeks. Tolerability was monitored throughout the study and up to 14 days after administration of the final dose. Primary end points were the proportions of patients with upper GI adverse events (AEs); upper GI AEs that were rated as serious or study drug related or that led to study discontinuation; and esophageal AEs. Between-treatment differences and associated 95% CIs were assessed using the Wilson score method. RESULTS: Of 438 patients who were randomized, 367 (mean age, 65.5 years; history of osteoporotic fracture, 6.8%; ALN monohydrate, 237; placebo, 130) completed the study. The proportion of patients with a history of upper GI disorders at baseline was numerically greater in the ALN monohydrate group than in the placebo group (117 [40.2%] and 45 [30.6%], respectively). The proportions of patients with active baseline upper GI disease were 83 (28.5%) and 30 (20.4%) in the ALN monohydrate and placebo groups, respectively. The proportions of patients who experienced an upper GI AE during the study period were 66 (22.7%) and 30 (20.4%) (95% CI, -6.2 to 10.0). The proportions of patients with upper GI AEs that were rated as serious or study drug related or that led to study discontinuation were 20.3% and 12.9% (95% CI, -0.3% to 14.1%). Three serious AEs in the active-treatment group (breast cancer, 2; wrist fracture, 1) were not considered related to the study drug, nor was the 1 serious AE in the placebo group (wrist fracture). One patient (ALN monohydrate) had an esophageal AE (nonserious spasm). Approximately 8% of patients who received ALN monohydrate reported dyspepsia, compared with none who received placebo. Within each treatment group, the rates of upper GI AEs were numerically higher in patients with a history of upper GI disease. CONCLUSIONS: In these postmenopausal women who received ALN monohydrate or placebo, upper GI AEs were common (20.4%-22.7%). The proportion of patients who experienced upper GI AEs considered drug related or that led to discontinuation was appar- ently greater with ALN monohydrate compared with placebo.

Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study.

OBJECTIVE: To compare the effects of alendronate (ALN) 70 mg once weekly (OW) and risedronate (RIS) 5 mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density (BMD) in postmenopausal women with osteoporosis. RESEARCH DESIGN AND METHODS: This was a 3-month, randomised, double-blind, placebo-controlled study with a double-blind extension to 12 months. The study enrolled 549 postmenopausal women (ALN 219, RIS 222 and placebo (PBO) 108) who were > or =60 years of age at outpatient centres. MAIN OUTCOME MEASURES: The primary endpoint was reduction in urine N-telopeptides of type 1 collagen (NTx) corrected for creatinine level at 3 months. Secondary parameters included change in BMD at the spine and hip at 6 and 12 months, NTx at 1, 6 and 12 months, and serum bone-specific alkaline phosphatase (BSAP) at 1, 3, 6 and 12 months. Adverse experiences (AEs) were recorded throughout the study for an assessment of treatment safety profiles and tolerability. RESULTS: Over 3 months, ALN produced a significantly greater mean reduction in urine NTx than did RIS (-52% vs -32%, p < 0.001), which was maintained at 12 months. ALN produced a significantly greater mean BMD increase than did RIS at 6 months, and it was maintained at 12 months at the lumbar spine (4.8% vs 2.8%, p < 0.001) and total hip (2.7% vs 0.9%, p < 0.001), as well as at the trochanter and femoral neck. Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment. Study size did not allow for meaningful assessment of differences in fracture rates. Tolerability was generally similar between ALN, RIS and PBO, and the incidence of upper GI AEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups. CONCLUSION: In this study, ALN 70 mg OW produced a 50% greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily. The treatments had similar safety profiles and were generally well-tolerated. Additional studies are needed comparing OW ALN with OW RIS, which became available after the commencement of the present study.