Improvement in sleep outcomes with a 17β-estradiol-progesterone oral capsule (TX-001HR) for postmenopausal women

Risa Kagan, Ginger Constantine, Andrew M Kaunitz, Brian Bernick, Sebastian Mirkin, Risa Kagan, Ginger Constantine, Andrew M Kaunitz, Brian Bernick, Sebastian Mirkin

Abstract

Objective: The aim of the study was to evaluate the effects of TX-001HR, a single-capsule 17β-estradiol-progesterone on sleep parameters in postmenopausal women with vasomotor symptoms (VMS) using the Medical Outcomes Study (MOS)-Sleep scale questionnaire in the REPLENISH trial.

Methods: In the REPLENISH trial (NCT01942668), women were randomized to one of four doses of TX-001HR or placebo, and the 12-item MOS-Sleep questionnaire (secondary endpoint) was self-administered at baseline, week 12, and months 6 and 12. Changes from baseline in the MOS-Sleep total score and 7 subscale scores were analyzed for treatment groups versus placebo at all time points. Somnolence was also collected as an adverse event.

Results: Women (mean age 55 y) were randomized to TX-001HR (estradiol/ progesterone [E2/P4] [mg/mg]) doses: 1/100 (n = 415), 0.5/100 (n = 424), 0.5/50 (n = 421), 0.25/50 (n = 424), or placebo (n = 151). TX-001HR significantly improved MOS-Sleep total score, Sleep Problems Index II subscale, and sleep disturbance subscale versus placebo at all time points, except with 0.25 mg E2/50 mg P4 at week 12. Differences in LS mean changes between TX-001HR and placebo for MOS-Sleep total scores ranged from -6.5 to -7.6 at 12 months (all; P ≤ 0.001). All doses of TX-001HR significantly improved the Sleep Problems Index I subscale at all time points. The sleep somnolence subscale significantly improved from baseline with 0.5 mg E2/100 mg P4 and 0.5 mg E2/50 mg P4 at month 12. The incidence of somnolence as a treatment-emergent adverse event ranged from 0.2% to 1.2% versus 0% with placebo.

Conclusion: TX-001HR significantly improved MOS-Sleep parameters from baseline to week 12, which was sustained for up to 12 months, and was associated with a very low incidence of somnolence.

Figures

FIG. 1
FIG. 1
Change from baseline at months 3, 6, and 12 with TX-001HR or placebo in (A) MOS-Sleep total score and MOS-Sleep subscales: (B) Sleep Problems Index I; (C) Sleep Problems Index II; (D) Sleep Disturbance; (E) Sleep Somnolence; (F) Sleep Adequacy; (G) Snoring; and (H) Sleep Shortness of Breath or Headache subscales. ∗P < 0.05; †P ≤ 0.01; ‡P ≤ 0.001 for TX-001HR versus placebo.

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