The Effect of Therapeutic and Supratherapeutic Oral Doses of Nomegestrol Acetate (NOMAC)/17β-Estradiol (E2) on QTcF Intervals in Healthy Women: Results from a Randomized, Double-Blind, Placebo- and Positive-Controlled Trial

Kam, Pieter-Jan de; Kuijk, J. van; Lillin, Otilia; Post, Teun M.; Thomsen, T.

doi:10.1007/s40261-014-0190-5

Cited by 3 publications

(3 citation statements)

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“…25 NOMAC/E2’s ability to prolong the QT interval was determined, in both therapeutic (2.5/1.5 mg) and supratherapeutic (12.5/7.5 mg) doses, in a thorough QT/QTc study. 26 This study’s design complied with the E14 guidance of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. 27 One hundred and eighty-nine healthy women aged 18–50 were randomized into one of four treatment groups – NOMAC/E2 2.5/1.5 mg (therapeutic dose), NOMAC/E2 12.5/7.5 mg (supratherapeutic dose), placebo, or minofloxacin.…”

Section: Safetymentioning

confidence: 99%

“…27 One hundred and eighty-nine healthy women aged 18–50 were randomized into one of four treatment groups – NOMAC/E2 2.5/1.5 mg (therapeutic dose), NOMAC/E2 12.5/7.5 mg (supratherapeutic dose), placebo, or minofloxacin. 26 A safety analysis was also done for all participants who received the study drug – any AEs, SAEs or death. One hundred and eighty-two women completed the study (mean age 35±9) with the seven discontinuations in the treatment groups having been due to personal reasons (two minofloxacin, one NOMAC/E2 2.5/1.5 mg), AEs (one minofloxacin, one placebo), and positive urinary drug test (one minofloxacin, one placebo).…”

Section: Safetymentioning

confidence: 99%

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Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

Akintomide¹,

Panicker²

2015

OAJC

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Nomegestrol acetate (NOMAC) 2.5 mg with 17-beta estradiol (E2) 1.5 mg is a new combined oral contraceptive (COC) formulation and is the first monophasic E2 pill to be marketed, having been licensed for use in Europe in 2011. It is available to be taken daily in a regimen of 24 active pills followed by four placebo pills. NOMAC is a highly selective 19-nor progestogen derivative with specific binding to progesterone receptors, anti-estrogenic activity and no androgenic, mineralocorticoid nor glucocorticoid effects. E2 is an estrogen that is identical to endogenous estrogen. While it has been in use for only a short period of time, current evidence suggests that NOMAC/E2 is just as effective, safe, and acceptable as existing COC preparations. Two large Phase III trials conducted in the Americas and across Europe, Australia, and Asia showed lower cumulative pregnancy rates in the NOMAC/E2 groups compared to the drospirenone (DRSP) 3 mg in combination with ethinyl estradiol (EE) 30 µg (DRSP/EE) groups but this difference was not statistically significant. NOMAC/E2 exhibits a good safety profile and has less effects on cardiovascular risk, hemostatic, metabolic, and endocrine factors in comparison to COCs containing EE in combination with levonorgestrel (LNG) or DRSP. NOMAC/E2 has also been found to cause less breast cell proliferation when compared to E2 alone and has some anti-proliferative effect on human breast cancer cells. NOMAC/E2 is considered acceptable as its compliance, continuation rates, and bleeding patterns were similar to COCs containing DRSP/EE and LNG 150 µg combined with EE 30 µg or LNG 100 µg combined with EE 20 µg (LNG/EE). However, discontinuation was found to be slightly higher in the NOMAC/E2 groups in the two large Phase III trials comparing NOMAC/E2 use with DRSP/EE. As the scientific literature has limited information on NOMAC/E2, further experience with NOMAC/E2 is required.

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Section: Safetymentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

Akintomide¹,

Panicker²

2015

OAJC

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“…A study of the effects of sex hormones on QTcF interval prolongation suggests that estrogen might be a risk factor for drug-induced torsades de pointes. Although E 2 may influence clinically relevant QT interval prolongation, the pathogenesis is still not clear [22]. …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

et al. 2016

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BackgroundLeuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.MethodsThis was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48.ResultsIn total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2 suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval −5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2 suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed.ConclusionsTAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).

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Hormonal therapy

De¹

2023

Medicines for Cancer

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The Effect of Therapeutic and Supratherapeutic Oral Doses of Nomegestrol Acetate (NOMAC)/17β-Estradiol (E2) on QTcF Intervals in Healthy Women: Results from a Randomized, Double-Blind, Placebo- and Positive-Controlled Trial

Abstract: This thorough QT/QTc study showed that therapeutic and supratherapeutic doses of NOMAC/E2 were not associated with clinically relevant QTc interval prolongation in healthy women after a 2-week period of dosing.

Cited by 3 publications

References 16 publications

Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

Hormonal therapy

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