title: The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy.
abstract: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy.
  
  
  
  In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia. Secondary endpoints included severity of vaginal dryness and vulvar and/or vaginal itching or irritation. Endometrial histology and adverse events (AEs) were included in the safety endpoints.
  
  
  
  In all, 764 women were randomized (modified intent-to-treat population, n = 747; mean age 59 y). Compared with placebo, all three doses of TX-004HR significantly improved the four co-primary endpoints (P < 0.0001 for all, except dyspareunia with 4 μg, P = 0.0149). Changes in cytology, pH, and dyspareunia were also significant at weeks 2, 6, and 8. Vaginal dryness and vaginal itching/irritation improved. Sex hormone binding globulin concentrations did not change with treatment. TX-004HR was well-tolerated, with no clinically meaningful differences in treatment-emergent AEs versus placebo, and no treatment-related serious AEs or deaths.
  
  
  
  TX-004HR (4, 10, and 25 μg) was safe, well-tolerated, and effective for treating moderate-to-severe dyspareunia within 2 weeks with minimal systemic estrogen exposure. This novel product may be a potential new treatment option for women experiencing postmenopausal vulvar and vaginal atrophy.
authors.affiliation: 1EndoRheum Consultants, LLC, Malvern, PA 2The George Washington University School of Medicine, Washington, DC 3Columbia University Medical Center, New York, NY 4Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA 5BioMedical Computer Research Institute, Inc, Philadelphia, PA 6TherapeuticsMD, Boca Raton, FL.
authors.forename: Ginger D
authors.initials: GD
authors.lastname: Constantine
authors.forename: James A
authors.initials: JA
authors.lastname: Simon
authors.forename: James H
authors.initials: JH
authors.lastname: Pickar
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Harvey
authors.initials: H
authors.lastname: Kushner
authors.forename: Brian
authors.initials: B
authors.lastname: Bernick
authors.forename: Gina
authors.initials: G
authors.lastname: Gasper
authors.forename: Shelli
authors.initials: S
authors.lastname: Graham
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mirkin
mesh_terms: D000282:Administration, Intravaginal; D000368:Aged; D001284:Atrophy / Q000150:complications / Q000188:drug therapy; D002214:Capsules; D004311:Double-Blind Method; D004414:Dyspareunia / Q000188:drug therapy* / Q000209:etiology; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008875:Middle Aged; D017698:Postmenopause; D011537:Pruritus / Q000188:drug therapy; D012720:Severity of Illness Index; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D014621:Vagina / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D014844:Vulva / Q000187:drug effects / Q000473:pathology*
chemical_list: D002214:Capsules; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol