A Study of Safety and Efficacy of Tildacerfont in Females With Polycystic Ovary Syndrome and Elevated Adrenal Androgens

Study Overview
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Brief Summary
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An investigation of the safety and efficacy of tildacerfont in women with PCOS and elevated adrenal androgens

Detailed Description
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This is a phase 2 study to evaluate the efficacy, safety and tolerability of 3 doses of tildacerfont in approximately 39 women with PCOS and elevated adrenal androgens assessed by elevated DHEAS levels. Subjects will be randomized 2:1 (tildacerfont:placebo) at baseline. The study will consist of 3 consecutive 4-week treatment periods at each dose level. Duration of participation is approximately 25 weeks.

Official Title
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A Randomized, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of Tildacerfont in Adult Subjects With Polycystic Ovary Syndrome (PCOS) and Elevated Adrenal Androgens

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Tildacerfont
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects aged 18 to 40 years old at Screening visit Diagnosis of PCOS (either historical or during Screening) according to NIH (1990) criteria DHEAS level > age-matched upper limit of normal (ULN) at Screening visit Agree to follow industry standard contraception guidelines within protocol Exclusion Criteria: Evidence of: History of congenital adrenal hyperplasia (CAH), Cushing's syndrome, pituitary or adrenal disease Clinically significant hyperprolactinemia Thyroid stimulating hormone (TSH) <0.1 mU/mL or >4.5mU/mL at Screening Cortisol levels concerning for adrenal insufficiency Other findings suggestive of secondary cause for anovulation and/or hyperandrogenemia Total testosterone levels >140 ng/dL, DHEAS >650 mcg/dL, virilization or other signs or symptoms concerning for ovarian hyperthecosis or androgen-secreting tumors Medical conditions that require glucocorticoid treatment within 30 days of screening and throughout the duration of the study Clinically significant unstable medical conditions, illness, or chronic diseases Prior hysterectomy or bilateral oophorectomy Females who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Tildacerfont<br>Subjects randomized in this arm will receive 4 weeks of 50mg of oral tildacerfont tablet, followed by 4 weeks of 100 mg oral tildacerfont tablet, and then 4 weeks of 200 mg oral tildacerfont tablet for a total of 12 weeks of treatment. | Drug: Tildacerfont<br>* Oral tablet formulation taken once daily.<br>* Other names: SPR001;|
| Placebo Comparator: Placebo Control Arm<br>Subjects randomized in this arm will receive 12 weeks of oral matched-placebo tablet | Drug: Placebo<br>* Non-active dosage form taken once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DHEAS level | Change from baseline in DHEAS level | 12 Weeks (assessed at Baseline, Weeks 4, 8, and 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in DHEAS | Proportion of subjects with >/=30% change from baseline in DHEAS | 12 weeks (assessed at Baseline, Weeks 4, 8 and 12) | 
| Normalization of DHEAS | Proportion of subjects with DHEAS =/< upper limit of normal for DHEAS | 12 weeks (assessed at Baseline, Weeks 4, 8 and 12) | 
| Number of subjects with TEAE as assessed by CTCAE Version 5 | Evaluation of safety of tildacerfont with PCOS as measured by number of subjects with adverse events following dosing by CTCAE Version 5 | 12 weeks (assessed at Baseline, Weeks 4, 8 and 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Womens health, PCOS, Elevated Adrenal Androgen, Adrenal Disorder, Polycystic Ovary Syndrome