TY - JOUR
T1 - The use of serum segesterone acetate levels to assess adherence of trial participants with a contraceptive vaginal ring
AU - Thompson, Rebecca L.
AU - Hu, Jack
AU - Custodio, Philip
AU - Dart, Clint
AU - Jensen, Jeffrey T.
N1 - Funding Information:
Declaration of Competing Interest: Dr. Jensen has received payments for consulting from Bayer Healthcare, Evofem, Hope Medicine, Foundation Consumer Healthcare, Mayne Pharma, ViiV Healthcare, and TherapeuticsMD. OHSU has received research support from Abbvie, Bayer Healthcare, Daré, Estetra SPRL, Hope Medicine, Medicines360, Merck, Myovent, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. The other authors have no potential conflicts. Funding: The study was supported by NICHD Contraception Clinical Trial Network: HHSN275201300008I/HHSN27500005 (Oregon Health and Science University).
Funding Information:
Funding: The study was supported by NICHD Contraception Clinical Trial Network: HHSN275201300008I/HHSN27500005 (Oregon Health and Science University).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/4
Y1 - 2022/4
N2 - Objectives: To determine the incidence of out-of-range segesterone acetate (NES) concentrations in participants of a pharmacokinetic/pharmacodynamic trial of a continuous use contraceptive vaginal ring (CVR) releasing NES and estradiol (E2). We hypothesized that out-of-range concentrations reflect nonadherent ring use and predict ovulation risk. Study Design: We conducted a secondary analysis of data from a prospective, multi-centered, randomized, Phase IIa dose-finding trial for a CVR releasing NES and E2. Our primary outcome was the risk of ovulation associated with out-of-range NES events. We calculated the 5th and 95th percentile NES concentrations of subjects at steady state to determine high and low cutoffs. We used a Fisher's exact test to determine group differences, and calculated the relative risk of ovulation for each group. Results: We analyzed available serum NES data from cycles 2 (n = 172), 3 (n = 156) and 7 (n = 115) to determine the 5th and 95th percentile of all NES concentrations (64, 296 pg/mL). In the 443 cycles of observation, no ovulations occurred in participants with NES concentrations within the expected range. In contrast, we found ovulatory elevations of progesterone in 21 cycles with out-of-range values. Of these, 15 (71%) cycles had evidence of one or more nonadherent low and 6 (29%) one or more unexpected peak. The relative risk of ovulation increased with evidence of multiple non-adherent levels. Conclusions: We found out-of-range NES concentrations, suggestive of improper use of a CVR associated with an increased risk of ovulation, with a direct relationship between the number of out-of-range events and the relative risk. Implications: The results of this study support the use of out-of-range serum NES values as a marker of adherence in contraceptive clinical trials of continuous vaginal rings, and suggest that nonadherence occurs even in early phase clinical trials with close monitoring.
AB - Objectives: To determine the incidence of out-of-range segesterone acetate (NES) concentrations in participants of a pharmacokinetic/pharmacodynamic trial of a continuous use contraceptive vaginal ring (CVR) releasing NES and estradiol (E2). We hypothesized that out-of-range concentrations reflect nonadherent ring use and predict ovulation risk. Study Design: We conducted a secondary analysis of data from a prospective, multi-centered, randomized, Phase IIa dose-finding trial for a CVR releasing NES and E2. Our primary outcome was the risk of ovulation associated with out-of-range NES events. We calculated the 5th and 95th percentile NES concentrations of subjects at steady state to determine high and low cutoffs. We used a Fisher's exact test to determine group differences, and calculated the relative risk of ovulation for each group. Results: We analyzed available serum NES data from cycles 2 (n = 172), 3 (n = 156) and 7 (n = 115) to determine the 5th and 95th percentile of all NES concentrations (64, 296 pg/mL). In the 443 cycles of observation, no ovulations occurred in participants with NES concentrations within the expected range. In contrast, we found ovulatory elevations of progesterone in 21 cycles with out-of-range values. Of these, 15 (71%) cycles had evidence of one or more nonadherent low and 6 (29%) one or more unexpected peak. The relative risk of ovulation increased with evidence of multiple non-adherent levels. Conclusions: We found out-of-range NES concentrations, suggestive of improper use of a CVR associated with an increased risk of ovulation, with a direct relationship between the number of out-of-range events and the relative risk. Implications: The results of this study support the use of out-of-range serum NES values as a marker of adherence in contraceptive clinical trials of continuous vaginal rings, and suggest that nonadherence occurs even in early phase clinical trials with close monitoring.
KW - Adherence
KW - Contraceptive vaginal ring
KW - Pharmacokinetic
KW - Segesterone acetate
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UR - http://www.scopus.com/inward/citedby.url?scp=85123872063&partnerID=8YFLogxK
U2 - 10.1016/j.contraception.2021.12.004
DO - 10.1016/j.contraception.2021.12.004
M3 - Article
C2 - 34971614
AN - SCOPUS:85123872063
SN - 0010-7824
VL - 108
SP - 61
EP - 64
JO - Contraception
JF - Contraception
ER -