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

Constantine, Ginger D.; Simon, James A.; Pickar, James H.; Archer, David F.; Kushner, Harvey; Bernick, Brian; Gasper, Gina; Graham, Shelli; Mirkin, Sebastián

doi:10.1097/gme.0000000000000786

Cited by 70 publications

(106 citation statements)

References 24 publications

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“…The study design for the REJOICE trial has been previously reported. 5 Women were randomized 1:1:1:1 to 4-, 10-, and 25- μ g TX-004HR or placebo. 5 Women self-administered 1 capsule per day intravaginally for 2 weeks, followed by bi-weekly dosing (3 to 4 days apart) for 10 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…5 Women were randomized 1:1:1:1 to 4-, 10-, and 25- μ g TX-004HR or placebo. 5 Women self-administered 1 capsule per day intravaginally for 2 weeks, followed by bi-weekly dosing (3 to 4 days apart) for 10 weeks. 5 Changes from baseline to week 12 in the percentages of superficial cells and parabasal cells, vaginal pH, and severity of the patient-reported MBS of moderate-to-severe dyspareunia were measured as co-primary endpoints.…”

Section: Methodsmentioning

confidence: 99%

“…5 Women self-administered 1 capsule per day intravaginally for 2 weeks, followed by bi-weekly dosing (3 to 4 days apart) for 10 weeks. 5 Changes from baseline to week 12 in the percentages of superficial cells and parabasal cells, vaginal pH, and severity of the patient-reported MBS of moderate-to-severe dyspareunia were measured as co-primary endpoints. 5 Secondary outcome measures included change from baseline to week 2, 6, and 8 in the same endpoints, as well as vaginal dryness and vulvar and/or vaginal itching or irritation.…”

Section: Methodsmentioning

confidence: 99%

“…The randomized, double-blind, phase 3 REJOICE trial recently demonstrated that TX-004HR at doses of 4, 10, and 25 μ g significantly improved the percentages of superficial cells by 17% to 23% versus 6% with placebo, parabasal cells by 41% to 46% versus 7%, vaginal pH by 1.3 to 1.4 versus 0.3, and severity of dyspareunia by 1.5 to 1.7 versus 1.3 in postmenopausal women with VVA after 12 weeks of treatment. 5 Significant improvements were observed as early as 2 weeks of treatment, 5 and with negligible to very low systemic absorption of estradiol. 6 All three doses also significantly reduced the severity of vaginal dryness and, with the exception of the 4 μ g dose, vulvar and/or vaginal itching/irritation when compared with placebo at 12 weeks.…”

Section: Introductionmentioning

confidence: 99%

“…6 All three doses also significantly reduced the severity of vaginal dryness and, with the exception of the 4 μ g dose, vulvar and/or vaginal itching/irritation when compared with placebo at 12 weeks. 5 …”

Section: Introductionmentioning

confidence: 99%

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Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women

Constantine¹,

Bouchard

Pickar

et al. 2017

Journal of Women's Health

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Background: The 12-week, randomized, double-blind, placebo-controlled, multicenter, phase 3 REJOICE trial demonstrated that TX-004HR, an investigational, applicator-free, low-dose vaginal softgel capsule containing solubilized 17β-estradiol, effectively and rapidly treats symptoms of vulvar and vaginal atrophy (VVA) with negligible to very low systemic absorption. The aim of this analysis was to assess whether the efficacy of TX-004HR varies with age, body mass index (BMI), uterine status, pregnancy status, and vaginal delivery.Methods: The REJOICE trial evaluated the efficacy of 4-, 10-, and 25-μg doses of TX-004HR in postmenopausal women (40–75 years) with VVA and a self-identified most bothersome symptom of moderate-to-severe dyspareunia. Prespecified subgroup analyses of the four co-primary endpoints (percentages of superficial cells and parabasal cells, vaginal pH, and severity of dyspareunia) were analyzed with respect to age, BMI, uterine status, pregnancy status, and vaginal births. Each dose was compared with placebo for change from baseline to week 2 through week 12, respectively.Results: TX-004HR significantly improved superficial cells, parabasal cells, and vaginal pH from baseline to weeks 2 and 12 in most subgroups. All TX-004HR doses numerically reduced the severity of dyspareunia by 2 weeks and maintained efficacy over 12 weeks, with many of the subgroups having statistically significant improvement relative to placebo.Conclusions: TX-004HR was efficacious for treating symptomatic VVA, and it demonstrated a consistency of effect when women's age, BMI, uterine status, pregnancy status, and vaginal births were evaluated. Clinical Trial Identifier: NCT02253173.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women

Constantine¹,

Bouchard

Pickar

et al. 2017

Journal of Women's Health

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Imvexxy – Another Estradiol Vaginal Insert for Dyspareunia

2019

JAMA

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The FDA has approved an estradiol softgel vaginal insert (Imvexxy -TherapeuticsMD) for treatment of postmenopausal women with moderate to severe dyspareunia due to vulvovaginal atrophy (VVA). Imvexxy is the second estradiol vaginal insert to be approved in the US; Vagifem, an intravaginal tablet formulation, was the first. 1 Vagifem and Imvexxy are both available in inserts containing 10 μg of estradiol; Imvexxy is also available in a 4-μg strength.

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Management of Menopausal Symptoms

Crandall

Mehta

Manson

2023

JAMA

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ImportanceMenopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]).ObservationsVasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene.Conclusions and RelevanceDuring the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.

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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: Supplemental Digital Content is available in the text

Cited by 70 publications

References 24 publications

Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women

Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women

Imvexxy – Another Estradiol Vaginal Insert for Dyspareunia

Management of Menopausal Symptoms

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