Study of Relugolix Alone and Relugolix Combined With Hormonal Add-Back Therapy in Healthy Premenopausal Female Participants

Study Overview
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Brief Summary
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This was a randomized, open-label, repeat dose study of once daily relugolix alone or relugolix combined with hormonal add-back therapy (combination estradiol/norethindrone acetate) (E2/NETA) to assess safety, including markers of bone resorption, pharmacokinetics (PK), and pharmacodynamics (PD) endpoints.

Official Title
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A Randomized Open Label Study to Evaluate the Safety, PK, and PD of Relugolix Alone and Relugolix Combined With Hormonal Add-Back Therapy for 6 Weeks in Healthy Premenopausal Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Relugolix
* Drug: E2/NETA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal female between 18 and 48 years of age. E2, P, LH and FSH concentrations within 0.5x of the lower limits of normal range and 2x of the upper limits of normal upper limits of normal range (ULN) Regular menstrual periods for the 3 months prior to study enrollment Body weight ≥ 45 killograms (kgs) and body mass index (BMI) of 20 to 36 Capable of giving written informed consent Exclusion Criteria: Pregnancy Lactating Females Any contraindication to the treatment with E2 and NETA Use of the following medications in the 3 months prior to screening: injectable hormonal contraceptives, sex hormone medications or danazol Use of the following medications in the 6 months prior to screening: injectable gonadotropin-releasing hormone agonists, hormonal, or non-hormonal intrauterine devices History of sensitivity to any of the study medications of components thereof or history of drug Significant gynecological, endocrine, metabolic or other health conditions History of regular alcohol consumption within 6 months of study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relugolix<br>Participants received relugolix 40 milligrams (mg) alone for 6 weeks. | Drug: Relugolix<br>* Administered as an oral tablet once daily.<br>|
| Experimental: Relugolix + E2/NETA<br>Participants received relugolix 40 mg and E2/NETA at 1 mg/ 0.5 mg for 6 weeks. | Drug: Relugolix<br>* Administered as an oral tablet once daily.<br>Drug: E2/NETA<br>* Administered as an oral tablet once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Area Under The Concentration-Time Curve From Time Zero To Hour 24 (AUC0-24) Of Relugolix, E2, Estrone (El), Ethinylestradiol (EE), NETA |  | Predose and up to 24 hours at Weeks 3 and 6 | 
| PK: Maximum Concentration (Cmax) Of Relugolix, E2, El, NETA |  | Predose and up to 24 hours at Weeks 3 and 6 | 
| PK: Time To Maximum Concentration (Tmax) Of Relugolix, E2, El, EE, NETA |  | Predose and up to 24 hours at Weeks 3 and 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Serum Follicle Stimulating Hormone (FSH) At Week 6 |  | Baseline, Week 6 | 
| Change From Baseline In Serum Luteinizing Hormone (LH) At Week 6 |  | Baseline, Week 6 | 
| Change From Baseline In Serum Progesterone (P) At Week 6 |  | Baseline, Week 6 | 
| Change From Baseline In Serum E2 And E1 At Week 6 |  | Baseline, Week 6 | 
| Change From Baseline In N-telopeptide And C-telopepetide Concentrations At Week 6 |  | Baseline, Week 6 | 
| Incidence Of Treatment-Emergent Adverse Events |  | 8 weeks | 
| Incidence Of Hot Flush |  | 8 weeks |