Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials.

Importance: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed.

Objective: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms.

Design, Setting, And Participants: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023).

Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause.

Objective: Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS.

Methods: The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance.

Absence of Drug-Drug Interaction of Anastrozole on Levonorgestrel Delivered Simultaneously by an Intravaginal Ring: Results of a Phase 2 Trial.

Intravaginal rings (IVRs) are an established option for continuous administration of drugs in women. The combination of anastrozole (ATZ) and levonorgestrel (LNG) in an IVR with an intended 4-week wearing period has been considered for long-term treatment of endometriosis-associated pelvic pain. A randomized, parallel-group, multicenter phase 2b study to assess the efficacy and safety of different dose combinations in women with symptomatic endometriosis has recently been performed.

Different Pearl Indices in studies of hormonal contraceptives in the United States: impact of study population.

Objective: To examine the impact of subject characteristics on efficacy as measured by the Pearl Index (PI) in clinical trials and to make study populations similar by matching.

Methods: Our analysis used US data from four large Phase III studies. We compared results from one fertility control patch study with pooled data from three studies with virtually identical design on oral hormonal contraceptives.

Effect of a low-dose contraceptive patch on efficacy, bleeding pattern, and safety: a 1-year, multicenter, open-label, uncontrolled study.

This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD.

Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea.

Objective: To demonstrate the superiority of estradiol valerate plus dienogest (E(2)V/DNG) over ethinylestradiol plus levonorgestrel (EE/LNG) in reducing the number of days with dysmenorrheic pain among women with primary dysmenorrhea.

Methods: In a phase IIIb trial conducted at 44 centers worldwide between April 2009 and November 2010, otherwise healthy women aged 14-50 years requesting contraception were randomized to daily oral administration of E(2)V/DNG (n = 253) or EE/LNG (n = 254) for three 28-daycycles. The primary efficacy variable was number of days with dysmenorrheic pain, the category of which (none, mild, moderate, severe) was self-assessed on a daily basis (irrespective of menstrual bleeding status) and recorded on diary cards.

Efficacy and safety of a combined oral contraceptive containing estradiol valerate/dienogest: results from a clinical study conducted in North America.

Background: This study investigated the efficacy and safety of a combined oral contraceptive (COC) containing estradiol valerate/dienogest (E2V/DNG).

Methods: This was a multicenter, noncomparative, 13-cycle (extended to 28 cycles) study conducted in the United States and Canada. Contraceptive efficacy was calculated as a Pearl Index for 13 cycles, based on all on-treatment pregnancies; bleeding patterns were calculated based on bleeding and spotting information recorded daily in diary cards.

Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction.

Introduction: It is a commonly held belief that combined oral contraceptive (COC) pills containing an androgenic progestin may be less likely to impair sexual function than COCs containing an anti-androgenic progestin.

Aim: The study aims to compare the effects of a COC containing a progestin with an anti-androgenic profile (estradiol valerate [E2 V]/dienogest [DNG]) to that of one with an androgenic progestin (ethinyl estradiol [EE]/levonorgestrel [LNG]) on sexual function in women with COC-associated sexual dysfunction.

Methods: In this multicenter, randomized, double-blind, noninferiority study, women with COC-associated female sexual dysfunction (FSD) were randomized to E2 V/DNG or EE/LNG for six cycles.

Efficacy and bleeding profile of a combined oral contraceptive containing oestradiol valerate/dienogest: a pooled analysis of three studies conducted in North America and Europe.

Objective: To summarise all clinical data on the contraceptive efficacy and bleeding profile associated with an oestradiol valerate (E2V) and dienogest (DNG) [E2V/DNG] combined oral contraceptive (COC) derived from Phase III trials.

Methods: Pooled analysis of three large-scale multicentre trials conducted in healthy women who received oral E2V/DNG for 7 to 28 cycles (28-day cycles).

Results: A total of 2266 women were included in this analysis.

Hormone withdrawal-associated symptoms: comparison of oestradiol valerate/dienogest versus ethinylestradiol/norgestimate.

Objectives: To determine the effect of oestradiol valerate/dienogest (E2V/DNG) versus ethinylestradiol/norgestimate (EE/NGM) on hormone-withdrawal associated symptoms (HWAS) in otherwise healthy women who had experienced at least one of these symptoms when using 21/7-day combined oral contraceptives (COCs).

Methods: This phase III, parallel-group study randomised 409 women aged 18 to 50 years to E2V/DNG or EE/NGM. The primary efficacy variable was the change from baseline to cycle 6 in the average of the three highest visual analogue scale values for headache and/or pelvic pain during cycle days 22 to 28.

Estimation of menstrual blood loss volume based on menstrual diary and laboratory data.

Background: Abnormal uterine bleeding is often investigated in clinical studies and critical to identify during gynecological consultation. The current standard for quantification of menstrual blood loss is the alkaline-hematin-method. However, this method is expensive and inconvenient for patients.

Evaluation of the effects of rifampicin, ketoconazole and erythromycin on the steady-state pharmacokinetics of the components of a novel oral contraceptive containing estradiol valerate and dienogest in healthy postmenopausal women.

Background: We evaluated the effects of cytochrome P450 3A4 (CYP3A4) induction and inhibition on steady-state pharmacokinetics of the components of a novel oral contraceptive (OC) containing estradiol valerate (E₂V) and dienogest (DNG).

Study Design: CYP3A4 induction was assessed in an open-label, one-arm study. Sixteen healthy postmenopausal women received E₂V 2 mg/DNG 3 mg (days 1-17) and concomitant rifampicin (600 mg, days 12-16).

Normalization of blood loss in women with heavy menstrual bleeding treated with an oral contraceptive containing estradiol valerate/dienogest.

Background: The study was conducted to assess the efficacy of estradiol valerate/dienogest (E₂V/DNG) administered using an estrogen step-down and progestogen step-up approach in a 28-day regimen in the treatment of heavy menstrual bleeding (HMB) using clinical end points allowing E₂V/DNG to be compared with other available medical therapies.

Study Design: This was a pooled analysis of data from two identically designed randomized, placebo-controlled, multiple center studies conducted in Europe, Australia and North America that assessed the effectiveness of E₂V/DNG in reducing menstrual blood loss (MBL) in women with HMB. Women aged ≥ 18 years with objectively confirmed HMB were randomized to E₂V/DNG (n=220) or placebo (n=135) for seven treatment cycles.

Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest.

Objectives: To evaluate the efficacy of oestradiol valerate/dienogest (E2V/DNG) for the treatment of heavy and/or prolonged menstrual bleeding without organic pathology based on the analysis of data from two identically designed double-blind, randomised studies.

Methods: Women aged ≥ 18 years with heavy and/or prolonged menstrual bleeding were randomised to E2V/DNG (n = 269) or placebo (n = 152) for 196 days. Objective changes in menstrual blood loss (MBL) volume were assessed using the alkaline haematin method.

Effect of extended-cycle regimen with an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on bleeding patterns, safety, acceptance and contraceptive efficacy.

Background: The present study compared the efficacy and safety of a combined oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year of treatment.

Study Design: In a phase III, randomized, prospective, open, two-arm, multicenter study, 1315 sexually active women (range, 18-40 years) were treated with EE/DNG either conventionally (21/7 days) or according to an extended-cycle regimen (84/7 days). Data were documented on volunteer diaries, and adverse events (AEs) were reported during five visits.

Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study.

Background And Objective: The hormonal components of combined oral contraceptives (COCs) have various metabolic and haemostatic effects. The objective of this study was to compare the metabolic and haemostatic effects of a novel COC comprising estradiol valerate/dienogest (E(2)V/DNG) with ethinylestradiol/levonorgestrel (EE/LNG).

Methods: In a randomized, open-label study conducted in Germany over seven cycles, healthy women aged 18-50 years received E(2)V/DNG (E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26, placebo on days 27-28; n = 30) or EE/LNG (EE 0.

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

Background: A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance.

Objective: The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel.

Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial.

Objective: To estimate the efficacy of a fixed estrogen step-down and progestin step-up 28-day estradiol (E2) valerate and dienogest oral contraceptive regimen in women with heavy menstrual bleeding, prolonged menstrual bleeding, or heavy and prolonged menstrual bleeding without organic pathology.

Methods: This double-blind, placebo-controlled study randomized women aged 18 years or older with prolonged, frequent, or heavy menstrual bleeding, objectively confirmed during a 90-day run-in phase, to treatment with E2 valerate and dienogest or placebo (2:1) for 196 days. Data from the last 90 days of treatment and the run-in phase were compared.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on lipid metabolism during 1 year of conventional or extended-cycle use.

Background: The effects of extended regimens of combined oral contraceptives (COC) on lipid parameters are largely unknown. The present study compared the effects of a COC containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year.

Study Design: Lipid parameters were measured in 59 women treated with EE/DNG either conventionally (21+7 days) or in extended-cycle regimen (84+7 days).

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

Background: This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol.

Study Design: This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.

Effects of conventional or extended-cycle regimen of an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on various hemostasis parameters.

Background: The study was conducted to investigate the effect of a combined oral contraceptive (COC) containing 30 mcg ethinylestradiol and 2 mg dienogest with two different regimens on various hemostasis variables.

Study Design: Hemostatic parameters were measured in 59 women treated with a monophasic COC containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or with an extended-cycle regimen (4 extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle or on Days 82-84 of the first and fourth extended cycle.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use.

Background: This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters.

Study Design: Thyroid and androgen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or according to an extended-cycle regimen (four extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle, or on Days 82-84 of the first and fourth extended cycle.

A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women.

Objectives: To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1mg estradiol valerate (1EV) and 2mg dienogest (2DNG) on the number of moderate and severe hot flushes.

Methods: This study compared the effects of an oral continuous-combined HT containing 1mg EV and 2mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks.