A Randomized Open-Label Study of Relugolix Alone or Relugolix Combination Therapy in Premenopausal Women.

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  • Additional Information
    • Source:
      Publisher: Country of Publication: Switzerland NLM ID: 7606849 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1926 (Electronic) Linking ISSN: 03125963 NLM ISO Abbreviation: Clin Pharmacokinet Subsets: MEDLINE
    • Publication Information:
      Publication: [Switzerland] : Adis, part of Springer Science+Business Media
      Original Publication: New York, ADIS Press.
    • Subject Terms:
      Norethindrone*/adverse effects ; Estradiol*/therapeutic use; Female ; Humans ; Norethindrone Acetate ; Phenylurea Compounds
    • Abstract:
      Background and Objective: Relugolix is a gonadotropin-releasing hormone receptor antagonist. Relugolix 40-mg monotherapy is associated with vasomotor symptoms and long-term bone mineral density loss due to hypoestrogenism. This study assessed whether the addition of estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg to relugolix 40 mg (relugolix combination therapy) provides systemic E2 concentrations in the 20-50 pg/mL range to minimize these undesirable effects.
      Methods: This was a randomized, open-label, parallel-group study to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of relugolix 40 mg alone or in combination with E2 1 mg and NETA 0.5 mg in healthy premenopausal women. Eligible women were randomized 1:1 to receive relugolix alone or relugolix plus E2/NETA for 6 weeks. Study assessments included pharmacokinetic parameters of E2, estrone, and relugolix in both treatment groups, and norethindrone in the relugolix plus E2/NETA treatment group at weeks 3 and 6.
      Results: Median E2 24 h average concentrations with the relugolix plus E2/NETA group (N = 23) were 31.5 pg/mL, 26 pg/mL higher compared with the relugolix-alone group (6.2 pg/mL) (N = 25). There were 86.4% of participants in the relugolix plus E2/NETA group who had E2 average concentrations exceeding 20 pg/mL, the threshold expected to minimize bone mineral density loss, compared with 21.1% in the relugolix-alone group. Both treatments were generally safe and well tolerated.
      Conclusions: Relugolix 40 mg in combination with E2 1 mg and NETA 0.5 mg provided systemic E2 concentrations within a range expected to minimize the risk of undesirable effects of hypoestrogenism associated with the administration of relugolix alone.
      Clinical Trial Registration: Clinicaltrials.gov identifier no. NCT04978688. Trial registration date: 27 July, 2021; retrospectively registered.
      (© 2023. The Author(s).)
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    • Molecular Sequence:
      ClinicalTrials.gov NCT04978688
    • Accession Number:
      0 (relugolix)
      T18F433X4S (Norethindrone)
      9S44LIC7OJ (Norethindrone Acetate)
      4TI98Z838E (Estradiol)
      0 (Phenylurea Compounds)
    • Publication Date:
      Date Created: 20230626 Date Completed: 20230731 Latest Revision: 20240922
    • Publication Date:
      20250114
    • Accession Number:
      PMC10386916
    • Accession Number:
      10.1007/s40262-023-01269-9
    • Accession Number:
      37365436