Dataset Information

Long-term tolerability of ethinylestradiol 20 ?g/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

ABSTRACT: This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 ?g/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens.In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres.Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ?1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens.EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

SUBMITTER: Klipping C

PROVIDER: S-EPMC3353878 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

Klipping Christine C Duijkers Ingrid I Fortier Michel P MP Marr Joachim J Trummer Dietmar D Elliesen Jörg J

The journal of family planning and reproductive health care 20120401 2

<h4>Background</h4>This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens.<h4>Study design</h4>In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRS ...[more]

PMID: 22454004

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Project description:The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 ?g/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen.This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only).Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles.EE 20 ?g/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.

Project description:OBJECTIVE:To evaluate the effect of a digital dispenser's acoustic alarm function on adherence to ethinylestradiol (EE) 20 ?g/drospirenone 3 mg in a flexible extended regimen (EE/drospirenoneFlex) among women in five European countries (France, Germany, Italy, Spain, UK) seeking oral contraception. STUDY DESIGN:Randomized, parallel-group open-label study. METHODS:Women aged 18-35 years received EE/drospirenoneFlex administered in a regimen with cycle lengths of their choice with the aid of a digital pill dispenser over 1 year. In group A (N=250), the dispenser's acoustic alarm was activated (ie, acoustic alarm + visual reminder). In group B (N=249), the acoustic alarm was deactivated (ie, visual reminder only). In addition, the women recorded pill intake daily in diary cards. The primary efficacy variable was the mean delay of daily pill release after the dispenser reminded the woman to take a pill (reference time). Secondary efficacy variables included number of missed pills, contraceptive efficacy, bleeding pattern, tolerability, and user satisfaction. RESULTS:Dispenser data showed a mean (standard deviation [SD]) daily delay in pill release of 88 (126) minutes in group A vs 178 (140) minutes in group B (P<0.0001). Median (lower quartile, Q1; upper quartile, Q3) number of missed pills was 0 (0; 1) in group A vs 4 (1; 9) in group B (P<0.0001). Diary card results revealed similar trends; however, underreporting of missed pills was evident in both groups. No pregnancies were reported during 424 women-years of exposure. Across the two groups, the mean (SD) EE/drospirenoneFlex cycle length was 51.0 (31.8) days with strong regional differences, and the mean (SD) number of bleeding/spotting days was 50.4 (33.0) days. EE/drospirenoneFlex was well tolerated, and 80% of women were satisfied with treatment. CONCLUSION:The dispenser's activated acoustic alarm improved adherence with daily tablet intake of EE/drospirenoneFlex, reducing missed pills. EE/drospirenoneFlex provided effective contraception and a good tolerability profile.

Project description:BackgroundDysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this indication in Japan.AimThe aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen) in Japanese women with dysmenorrhea.MethodsThis multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 μg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24-120 days followed by a 4-day tablet-free interval) or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles). The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed.ResultsA total of 216 women (mean age 29.7 years) were randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107). Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in disease severity reported in both treatment groups. According to the investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen treatment groups had "very much improved" or "much improved" disease, while 54.3% and 50.9% of patients reported being "very much satisfied" or "much satisfied" with their treatment, respectively.ConclusionIn Japanese women with dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone decreased the number of days with dysmenorrheic pain versus the traditional 28d regimen.

Project description:IntroductionDysmenorrhea and endometriosis are common gynecologic disorders among women of reproductive age that significantly impact health-related quality of life (HRQL) as well as productivity. Although there are treatment options listed in Japanese guidelines, a gap remains in unmet medical needs for maximizing treatment outcome. The extended regimen of ethinylestradiol and drospirenone (EE/DRSP) (taken daily for up to 120 consecutive days) has been available in Japan for treating dysmenorrhea and/or endometriosis-associated pain since 2016. Yet, the effectiveness of its usage on HRQL has not been investigated elsewhere to date. Therefore, in this study, we aim to observe changes in HRQL of Japanese women treated with an extended regimen of EE/DRSP for dysmenorrhea and/or endometriosis-associated pain.MethodsAs part of a 2-year post-marketing surveillance study, women with dysmenorrhea or endometriosis-associated pelvic pain were prescribed extended EE/DRSP during routine clinical practice. Data were collected 1 month before and 3 and 6 months after initiating treatment. Primary outcomes were the Menstrual Distress Questionnaire (MDQ) (before, during, and after menstruation) in patients with dysmenorrhea, and the Endometriosis Impact Scale (EIS) and European Quality of Life 5-dimensions 5-level instrument (EQ-5D-5L) in patients with endometriosis.ResultsThe study cohort included 315 patients (mean age 28.9 years) with dysmenorrhea and 262 patients (mean age 31.3 years) with endometriosis. Mean MDQ total scores before and during menstruation decreased significantly after 6 months with extended EE/DRSP; there was no improvement in after-menstruation MDQ score. Mean EIS domain scores improved significantly by 6 months, with improvement in most EIS individual item scores. Mean EQ-5D-5L scores increased slightly during 6 months of treatment.ConclusionsExtended EE/DRSP treatment improved HRQL outcomes in Japanese women with dysmenorrhea or endometriosis-associated pelvic pain.Trial registrationRegistered at ClinicalTrials.gov (NCT03126747) on June 2017.

Project description:Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.

Dataset Information

Long-term tolerability of ethinylestradiol 20 ?g/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

Publications

Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

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