A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms

Summary

This study will be a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial of postmenopausal subjects with an intact uterus.

Timeline

Start

2013-08-05

Primary completion

2016-10-28

Completion

2016-10-28

Outcome

Mixed primary results

registry analysis (superiority test); Combined Estradiol 1 mg / Progesterone 100 mg vs Placebo; p <0.001; Mean Difference (Final Values) -12.81 (95% CI -19.29 to -6.32) NCT01942668 ↗

registry analysis (superiority test); Combined Estradiol 0.5 mg / Progesterone 50 mg vs Placebo; p = 0.141; Mean Difference (Final Values) -4.81 (95% CI -11.21 to 1.59) NCT01942668 ↗

release “TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg both achieved all four of the co-primary efficacy endpoints” therapeuticsmd.com ↗

release “TX-001HR estradiol 0.5 mg/progesterone 50 mg and TX-001HR estradiol 0.25 mg/progesterone 50 mg were not statistically significant at all of the co-primary efficacy endpoints” therapeuticsmd.com ↗

Publications

• Background Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161-75. doi: 10.1016/s0378-5122(96)82006-8.
• Background Gerlinger C, Gude K, Hiemeyer F, Schmelter T, Schafers M. An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women. Menopause. 2012 Jul;19(7):799-803. doi: 10.1097/gme.0b013e31823de8ba.
• Background Spritzer, K. L. & Hays, R. D. (2003, November). MOS Sleep Scale: A Manual for Use and Scoring, Version 1.0. Los Angeles, CA.
• Background Kurman RJ, Ellenson L H, and Ronnett B.M., ed. Blaustein's Pathology of the Female Genital Tract. 6th ed. New York, NY: Springer; 2011:305-452.
• Background Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008 Feb;61(2):102-9. doi: 10.1016/j.jclinepi.2007.03.012. Epub 2007 Aug 3.
• Background Hays RD and Stewart AL. Sleep measures. In AL Stewart & JE Ware (eds), Measuring functioning and well-being: The Medical Outcomes Study approach (pp 235-259). Durham, NC: Duke University Press, 1992.
• McClung MR, Kagan R, Graham S, Bernick B, Mirkin S, Constantine G. Effects of E2/P4 oral capsules on bone turnover in women with vasomotor symptoms. Menopause. 2022 Feb 14;29(3):304-308. doi: 10.1097/GME.0000000000001915.
• Constantine GD, Simon JA, Kaunitz AM, Pickar JH, Revicki DA, Graham S, Bernick B, Mirkin S. TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial. Menopause. 2020 Nov;27(11):1236-1241. doi: 10.1097/GME.0000000000001602.
• Black DR, Minkin MJ, Graham S, Bernick B, Mirkin S. Effects of combined 17beta-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial. Menopause. 2020 Sep 14;28(1):32-39. doi: 10.1097/GME.0000000000001659.
• Kaunitz AM, Bitner D, Constantine GD, Bernick B, Graham S, Mirkin S. 17beta-estradiol/progesterone in a single, oral, softgel capsule (TX-001HR) significantly increased the number of vasomotor symptom-free days in the REPLENISH trial. Menopause. 2020 Dec;27(12):1382-1387. doi: 10.1097/GME.0000000000001615.
• Mirkin S, Goldstein SR, Archer DF, Pickar JH, Graham S, Bernick B. Endometrial safety and bleeding profile of a 17beta-estradiol/progesterone oral softgel capsule (TX-001HR). Menopause. 2020 Apr;27(4):410-417. doi: 10.1097/GME.0000000000001480.
• Lobo RA, Kaunitz AM, Santoro N, Bernick B, Graham S, Mirkin S. Metabolic and cardiovascular effects of TX-001HR in menopausal women with vasomotor symptoms. Climacteric. 2019 Dec;22(6):610-616. doi: 10.1080/13697137.2019.1640197. Epub 2019 Jul 31.
• Mirkin S, Graham S, Revicki DA, Bender RH, Bernick B, Constantine GD. Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17beta-estradiol/progesterone. Menopause. 2019 Jan 9;26(6):637-642. doi: 10.1097/GME.0000000000001294.
• Kagan R, Constantine G, Kaunitz AM, Bernick B, Mirkin S. Improvement in sleep outcomes with a 17beta-estradiol-progesterone oral capsule (TX-001HR) for postmenopausal women. Menopause. 2018 Dec 21;26(6):622-628. doi: 10.1097/GME.0000000000001278.
• Lobo RA, Archer DF, Kagan R, Kaunitz AM, Constantine GD, Pickar JH, Graham S, Bernick B, Mirkin S. A 17beta-Estradiol-Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women: A Randomized Controlled Trial. Obstet Gynecol. 2018 Jul;132(1):161-170. doi: 10.1097/AOG.0000000000002645.
• Mirkin S, Amadio JM, Bernick BA, Pickar JH, Archer DF. 17beta-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. Maturitas. 2015 May;81(1):28-35. doi: 10.1016/j.maturitas.2015.02.266. Epub 2015 Mar 9.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Estradiol	Other / unclassified	0.25 mg	Oral
Subject	Estradiol	Other / unclassified	0.5 mg	Oral
Subject	Estradiol	Other / unclassified	1 mg	Oral
Subject	Progesterone	Other / unclassified	50 mg	Oral
Subject	Progesterone	Other / unclassified	100 mg	Oral

Indications

No indication recorded.