Estradiol and progesterone bioavailability for moderate to severe vasomotor symptom treatment and endometrial protection with the continuous-combined regimen of TX-001HR (oral estradiol and progesterone capsules).
Menopause
; 26(7): 720-727, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-30694918
ABSTRACT
OBJECTIVE:
In the REPLENISH trial, women receiving TX-001HR-an oral, softgel capsule, combining 17ß-estradiol (E2) and progesterone (E2 mg/P4 mg 1/100, 0.5/100), had significantly improved vasomotor symptoms, while having their endometrium protected from hyperplasia. The objective here was to describe P4 levels sufficient to counteract the potential endometrial effects of 1 or 0.5âmg oral E2 with TX-001HR.METHODS:
In REPLENISH (phase 3; NCT01942668), serum P4, E2, and estrone (E1) levels were characterized in postmenopausal women treated with TX-001HR (E2 mg/P4 mg 1/100, 0.5/100, [0.5/50, 0.25/50 and placebo not reported here]) at baseline, week 12, and month 12 for P4, and at baseline, weeks 4 and 12, and months 6, 9, and 12 for E2 and E1. In a phase 1 study, pharmacokinetic parameters were assessed after 7 daily doses of oral E2 mg/P4 mg (1/100 and 0.5/100).RESULTS:
In REPLENISH (nâ=â1,835), mean P4 levels were 0.39 to 0.55âng/mL with 100-mg P4 doses; E2 levels were 42.3 to 45.6âpg/mL and 23.0 to 27.4âpg/mL for the 1-mg and 0.5-mg E2 doses, respectively; E1 levels were 214 to 242âpg/mL and 114 to 129âpg/mL for the 1-mg and 0.5-mg E2 doses. In the phase 1 study (nâ=â40; day 7), mean Cavg for P4 was 0.66âng/mL with 100-mg P4 doses; E2 was 38.1âpg/mL and 29.2âpg/mL for 1âmg and 0.5âmg E2, respectively; and E1 was 211 and 106âpg/mL for 1âmg and 0.5âmg E2. All three analytes reached steady state within 7 days; accumulation ratios were 1.36 to 1.94.CONCLUSIONS:
P4 levels observed with TX-001HR were similar in the phase 1 and 3 studies, and were associated with no endometrial hyperplasia with either E2 daily dose over 1 year in the REPLENISH phase 3 study, which showed significant improvements in menopausal vasomotor symptoms.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Progesterona
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Posmenopausia
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Hiperplasia Endometrial
/
Estradiol
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
Límite:
Adult
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Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Menopause
Asunto de la revista:
GINECOLOGIA
Año:
2019
Tipo del documento:
Article