PMID- 27922936
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20220330
IS  - 1530-0374 (Electronic)
IS  - 1072-3714 (Print)
IS  - 1072-3714 (Linking)
VI  - 24
IP  - 4
DP  - 2017 Apr
TI  - 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.
PG  - 409-416
LID - 10.1097/GME.0000000000000786 [doi]
AB  - OBJECTIVE: 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. METHODS: 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 mug 
      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. 
      RESULTS: 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 mug, 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. CONCLUSIONS: TX-004HR (4, 10, and 25 mug) 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.
FAU - Constantine, Ginger D
AU  - Constantine GD
AD  - 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.
FAU - Simon, James A
AU  - Simon JA
FAU - Pickar, James H
AU  - Pickar JH
FAU - Archer, David F
AU  - Archer DF
FAU - Kushner, Harvey
AU  - Kushner H
FAU - Bernick, Brian
AU  - Bernick B
FAU - Gasper, Gina
AU  - Gasper G
FAU - Graham, Shelli
AU  - Graham S
FAU - Mirkin, Sebastian
AU  - Mirkin S
CN  - REJOICE Study Group
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Menopause
JT  - Menopause (New York, N.Y.)
JID - 9433353
RN  - 0 (Capsules)
RN  - 0 (Estrogens)
RN  - 0 (Sex Hormone-Binding Globulin)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Administration, Intravaginal
MH  - Aged
MH  - Atrophy/complications/drug therapy
MH  - Capsules
MH  - Double-Blind Method
MH  - Dyspareunia/*drug therapy/etiology
MH  - Estradiol/adverse effects/*therapeutic use
MH  - Estrogens/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Hydrogen-Ion Concentration/drug effects
MH  - Middle Aged
MH  - Postmenopause
MH  - Pruritus/drug therapy
MH  - Severity of Illness Index
MH  - Sex Hormone-Binding Globulin/metabolism
MH  - Vagina/chemistry/drug effects/*pathology
MH  - Vulva/drug effects/*pathology
PMC - PMC5367497
EDAT- 2016/12/07 06:00
MHDA- 2018/02/23 06:00
PMCR- 2017/03/27
CRDT- 2016/12/07 06:00
PHST- 2016/12/07 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2016/12/07 06:00 [entrez]
PHST- 2017/03/27 00:00 [pmc-release]
AID - MENO-D-16-00192 [pii]
AID - 10.1097/GME.0000000000000786 [doi]
PST - ppublish
SO  - Menopause. 2017 Apr;24(4):409-416. doi: 10.1097/GME.0000000000000786.