Dataset Information

Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain.

ABSTRACT: Elagolix is a novel oral gonadotropin releasing hormone receptor antagonist, that can suppress estradiol in a dose-dependent manner. It is indicated for management of moderate-to-severe pain associated with endometriosis. A population exposure-response model describing the relationship between elagolix exposure and changes in bone mineral density (BMD) was developed using data from four phase III studies in premenopausal women with endometriosis-associated pain. Elagolix pharmacokinetic exposure-dependent changes in BMD were described by an indirect-response maximum effect (Emax ) model through stimulation of bone resorption. African American race, higher body mass index (BMI), and lower type-I collagen C-telopeptide concentrations were significantly associated with higher baseline BMD. Higher BMI was significantly associated with higher bone formation rates. Simulations using the final model demonstrated that elagolix 150 mg q.d. dosing for 24 months is predicted to result in -1.45% (-2.04 to -0.814) decrease from baseline in BMD and were used to support corresponding dosing recommendations in the label.

SUBMITTER: Abbas Suleiman A

PROVIDER: S-EPMC7679073 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain.

Abbas Suleiman Ahmed A Nader Ahmed A Winzenborg Insa I Beck Denise D Polepally Akshanth R AR Ng Juki J Noertersheuser Peter P Mostafa Nael M NM

CPT: pharmacometrics & systems pharmacology 20201008 11

Elagolix is a novel oral gonadotropin releasing hormone receptor antagonist, that can suppress estradiol in a dose-dependent manner. It is indicated for management of moderate-to-severe pain associated with endometriosis. A population exposure-response model describing the relationship between elagolix exposure and changes in bone mineral density (BMD) was developed using data from four phase III studies in premenopausal women with endometriosis-associated pain. Elagolix pharmacokinetic exposure ...[more]

PMID: 32945631

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Project description:ObjectiveIn this post hoc analysis, we evaluated the impact of elagolix on dysmenorrhea and nonmenstrual pelvic pain across menstrual period (bleeding days) and nonmenstrual (nonbleeding) days.MethodsData from two randomized, 6-month, placebo-controlled trials (Elaris Endometriosis (EM)-I and EM-II) of elagolix (150 mg once daily (QD) and 200 mg twice daily (BID)) in premenopausal women with moderate to severe endometriosis-associated pain (N = 1686) were pooled. Women recorded the presence of menstrual period and severity of dysmenorrhea or nonmenstrual pelvic pain in a daily electronic diary.ResultsAt baseline, women in the placebo group and both elagolix treatment groups reported moderate or severe dysmenorrhea, on average, 81% of their menstrual period days and moderate/severe nonmenstrual pelvic pain, on average, 56% of their nonmenstrual (nonbleeding) days. Compared with placebo at month 6, elagolix-treated women had a significantly lower mean (standard deviation (SD)) percentage of menstrual period days with moderate or severe dysmenorrhea (elagolix 150 mg QD = 52.4 (38.9), p = 0.002; elagolix 200 mg BID = 38.5 (43.6), p < 0.001, placebo = 61.3 (33.7)) and a significantly lower mean (SD) percentage of nonmenstrual (nonbleeding) days with moderate or severe nonmenstrual pelvic pain (elagolix 150 mg QD = 31.1 (35.8), p < 0.001; elagolix 200 mg BID = 19.7 (29.9), p < 0.001; placebo = 35.6 (33.9)).ConclusionFollowing 6 months of elagolix treatment, women who still menstruated had a lower proportion of menstrual period days with moderate or severe dysmenorrhea compared with placebo, demonstrating pain reduction despite continued menses. Additionally, pain did not shift from dysmenorrhea to nonmenstrual pelvic pain, as the percentage of days with moderate or severe nonmenstrual pelvic pain was also reduced for elagolix-treated women compared with placebo.Trial registrationThe Elaris EM-I study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01620528. The Elaris EM-II study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01931670. Both studies are registered with the EU Clinical Trial Register, www.clinicaltrialsregister.ed, 2011-004295-11.

Project description:ObjectiveTo evaluate the effects of elagolix on clinically meaningful improvements in health-related quality of life (HRQOL) measured by the EHP-30 (Endometriosis Health Profile-30).MethodsData from two phase III trials of elagolix for moderate to severe pain associated with endometriosis were pooled and analyzed as three groups: placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. Patients were administered the EHP-30 questionnaire at baseline, and at months 1, 3, and 6 of treatment. Previously established responder definitions were applied to determine percentages of patients with clinically meaningful EHP-30 improvements. The probability of meeting EHP-30 responder definitions with elagolix compared with placebo at months 3 and 6 was determined by Poisson regression analysis, controlling for baseline scores.ResultsAt month 6, the probabilities of meeting EHP-30 subscale responder definitions for pain, control and powerlessness, self-image, social support, emotional well-being, and sexual intercourse were 169% (adjusted relative risk [aRR]: 2.69, 95% CI 2.26-3.21), 129% (aRR 2.29, 95% CI 1.96-2.67), 80% (aRR 1.80, 95% CI 1.54-2.11), 70% (aRR 1.70, 95% CI 1.47-1.97), 67% (aRR 1.67, 95% CI 1.45-1.92), and 62% (aRR 1.62, 95% CI 1.36-1.92) greater, respectively (all P<.001), in the 200-mg group than in the placebo group. Although lower in magnitude than the 200-mg group, the 150-mg group also had greater probabilities of meeting responder definitions than the placebo group for all subscales except sexual intercourse. The probabilities of meeting responder definitions for pain, control and powerlessness, self-image, social support, and emotional well-being were 75% (aRR 1.75, 95% CI 1.44-2.14), 50% (aRR 1.50, 95% CI 1.25-1.80), 22% (aRR 1.22, 95% CI 1.01-1.47), 30% (aRR 1.30, 95% CI 1.09-1.53), and 35% (aRR 1.35, 95% CI 1.16-1.57) greater, respectively (all P<.05), in the 150-mg group than in the placebo group.ConclusionPatients with moderate to severe pain associated with endometriosis and were treated with elagolix experienced clinically meaningful HRQOL improvements.Clinical trial registrationClinicalTrials.gov, NCT01620528 and NCT01931670.Funding sourceAbbVie Inc.

Dataset Information

Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain.

Publications

Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain.

Similar Datasets

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