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

Phase 2

Terminated

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

Detailed Description: This was 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 were randomized 2:1 (tildacerfont:placebo) at baseline. The study consisted of 3 consecutive 4-week treatment periods at each dose level. Duration of participation was approximately 25 weeks.

Recruitment & Eligibility

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:
1. History of congenital adrenal hyperplasia (CAH), Cushing's syndrome, pituitary or adrenal disease
2. Clinically significant hyperprolactinemia
3. Thyroid stimulating hormone (TSH) <0.1 mU/mL or >4.5mU/mL at Screening
4. Cortisol levels concerning for adrenal insufficiency
5. 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

Arm && Interventions

Group	Intervention	Description
Treatment with Tildacerfont	Tildacerfont	Subjects randomized in this arm received 4 weeks of 50 mg 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.
Placebo Control Arm	Placebo	Subjects randomized in this arm received 12 weeks of oral matched-placebo tablet

Primary Outcome Measures

Name	Time	Method
Change in DHEAS	12 weeks (assessed at Baseline, Weeks 4, 8 and 12)	To evaluate the effect of tildacerfont in changing (reducing) DHEAS in subjects with PCOS and elevated adrenal androgens

Secondary Outcome Measures

Name	Time	Method
Reduction in DHEAS	12 weeks (assessed at Baseline, Weeks 4, 8 and 12)	Number of subjects with \>/=30% change from baseline in DHEAS
Normalization of DHEAS	12 weeks (assessed at Baseline, Weeks 4, 8 and 12)	Number of subjects with DHEAS =/\< upper limit of normal for DHEAS
Number of Subjects With TEAE as Assessed by CTCAE Version 5	12 weeks (assessed at Baseline, Weeks 4, 8 and 12)	Evaluation of safety of tildacerfont with PCOS as measured by number of subjects with adverse events following dosing by CTCAE Version 5