Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation

Kristina Gemzell-Danielsson, Regine Sitruk-Ware, Mitchell D Creinin, Michael Thomas, Kurt T. Barnhart, George Creasy, Heather Sussman, Mohcine Alami, Anne E. Burke, Edith Weisberg, Ian Fraser, Marie José Miranda, Melissa Gilliam, James Liu, Bruce R. Carr, Marlena Plagianos, Kevin Roberts, Diana Blithe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. Study design: We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. Results: The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m 2 ] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26%), nausea (n=420, 18%), vaginal discharge/vulvovaginal mycotic infection (n=242, 10%) and abdominal pain (n=225, 10%). Few (<1.5%) women discontinued for these complaints. Four (0.2%) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m 2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. Conclusion: The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. Implications: This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.

Original languageEnglish (US)
JournalContraception
DOIs
StatePublished - Jan 1 2019

Fingerprint

Ethinyl Estradiol
Contraceptive Agents
Acetates
Safety
Vaginal Discharge
Microbiology
Nausea
Abdominal Pain
Prescriptions
Headache
Body Mass Index
Pharmacokinetics
Outcome Assessment (Health Care)
Biopsy

Keywords

  • Adverse events
  • Contraceptive vaginal system
  • Ethinyl estradiol
  • Nestorone
  • Segesterone acetate

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation. / Gemzell-Danielsson, Kristina; Sitruk-Ware, Regine; Creinin, Mitchell D; Thomas, Michael; Barnhart, Kurt T.; Creasy, George; Sussman, Heather; Alami, Mohcine; Burke, Anne E.; Weisberg, Edith; Fraser, Ian; Miranda, Marie José; Gilliam, Melissa; Liu, James; Carr, Bruce R.; Plagianos, Marlena; Roberts, Kevin; Blithe, Diana.

In: Contraception, 01.01.2019.

Research output: Contribution to journalArticle

Gemzell-Danielsson, K, Sitruk-Ware, R, Creinin, MD, Thomas, M, Barnhart, KT, Creasy, G, Sussman, H, Alami, M, Burke, AE, Weisberg, E, Fraser, I, Miranda, MJ, Gilliam, M, Liu, J, Carr, BR, Plagianos, M, Roberts, K & Blithe, D 2019, 'Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation', Contraception. https://doi.org/10.1016/j.contraception.2019.02.001
Gemzell-Danielsson, Kristina ; Sitruk-Ware, Regine ; Creinin, Mitchell D ; Thomas, Michael ; Barnhart, Kurt T. ; Creasy, George ; Sussman, Heather ; Alami, Mohcine ; Burke, Anne E. ; Weisberg, Edith ; Fraser, Ian ; Miranda, Marie José ; Gilliam, Melissa ; Liu, James ; Carr, Bruce R. ; Plagianos, Marlena ; Roberts, Kevin ; Blithe, Diana. / Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation. In: Contraception. 2019.
@article{ee7436e5d3c942d0aba8d2f16d04e9fe,
title = "Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation",
abstract = "Objectives: To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. Study design: We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. Results: The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m 2 ] received the final manufactured CVS, of whom 999 (43.3{\%}) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26{\%}), nausea (n=420, 18{\%}), vaginal discharge/vulvovaginal mycotic infection (n=242, 10{\%}) and abdominal pain (n=225, 10{\%}). Few (<1.5{\%}) women discontinued for these complaints. Four (0.2{\%}) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m 2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5{\%}) cycles and complete expulsions in 1509 (7{\%}) cycles, most frequently in the initial cycle [499/2050 (24.3{\%}) and 190/2050 (9.3{\%}), respectively]. Safety-focused studies revealed no safety concerns. Conclusion: The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. Implications: This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.",
keywords = "Adverse events, Contraceptive vaginal system, Ethinyl estradiol, Nestorone, Segesterone acetate",
author = "Kristina Gemzell-Danielsson and Regine Sitruk-Ware and Creinin, {Mitchell D} and Michael Thomas and Barnhart, {Kurt T.} and George Creasy and Heather Sussman and Mohcine Alami and Burke, {Anne E.} and Edith Weisberg and Ian Fraser and Miranda, {Marie Jos{\'e}} and Melissa Gilliam and James Liu and Carr, {Bruce R.} and Marlena Plagianos and Kevin Roberts and Diana Blithe",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.contraception.2019.02.001",
language = "English (US)",
journal = "Contraception",
issn = "0010-7824",
publisher = "Elsevier USA",

}

TY - JOUR

T1 - Segesterone acetate/ethinyl estradiol 12-month contraceptive vaginal system safety evaluation

AU - Gemzell-Danielsson, Kristina

AU - Sitruk-Ware, Regine

AU - Creinin, Mitchell D

AU - Thomas, Michael

AU - Barnhart, Kurt T.

AU - Creasy, George

AU - Sussman, Heather

AU - Alami, Mohcine

AU - Burke, Anne E.

AU - Weisberg, Edith

AU - Fraser, Ian

AU - Miranda, Marie José

AU - Gilliam, Melissa

AU - Liu, James

AU - Carr, Bruce R.

AU - Plagianos, Marlena

AU - Roberts, Kevin

AU - Blithe, Diana

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. Study design: We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. Results: The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m 2 ] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26%), nausea (n=420, 18%), vaginal discharge/vulvovaginal mycotic infection (n=242, 10%) and abdominal pain (n=225, 10%). Few (<1.5%) women discontinued for these complaints. Four (0.2%) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m 2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. Conclusion: The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. Implications: This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.

AB - Objectives: To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. Study design: We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. Results: The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m 2 ] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26%), nausea (n=420, 18%), vaginal discharge/vulvovaginal mycotic infection (n=242, 10%) and abdominal pain (n=225, 10%). Few (<1.5%) women discontinued for these complaints. Four (0.2%) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m 2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. Conclusion: The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. Implications: This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.

KW - Adverse events

KW - Contraceptive vaginal system

KW - Ethinyl estradiol

KW - Nestorone

KW - Segesterone acetate

UR - http://www.scopus.com/inward/record.url?scp=85063444853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063444853&partnerID=8YFLogxK

U2 - 10.1016/j.contraception.2019.02.001

DO - 10.1016/j.contraception.2019.02.001

M3 - Article

JO - Contraception

JF - Contraception

SN - 0010-7824

ER -