Polycystic Ovary Syndrome
Conditions
Keywords
PCOS, Elevated Adrenal Androgen, Adrenal Disorder, Polycystic Ovary Syndrome, Womens health
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.
Interventions
DRUGTildacerfont
Oral tablet formulation taken once daily.
DRUGPlacebo
Non-active dosage form taken once daily.
Sponsors
Spruce Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind randomization performed by IRT
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Of the 82 subjects that were screened, a total of 27 subjects enrolled in the study (10 subjects in the placebo arm and 17 subjects in the tildacerfont arm).
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Tildacerfont 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. | 17 |
| Placebo Control Arm Subjects randomized in this arm will receive 12 weeks of oral matched-placebo tablet | 10 |
| Total | 27 |
Baseline characteristics
| Characteristic | Total | Treatment With Tildacerfont | Placebo Control Arm |
|---|---|---|---|
| 17-hydroxyprogesterone (17-OHP) | 75.4 ng/dL STANDARD_DEVIATION 75.51 | 83.2 ng/dL STANDARD_DEVIATION 86.28 | 62.1 ng/dL STANDARD_DEVIATION 54.1 |
| Adrenocorticotropic hormone (ACTH) | 23.27 pg/dL STANDARD_DEVIATION 11.744 | 23.88 pg/dL STANDARD_DEVIATION 11.927 | 22.3 pg/dL STANDARD_DEVIATION 12.013 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 17 Participants | 10 Participants |
| Androstenedione (A4) | 166.8 ng/dL STANDARD_DEVIATION 75.61 | 185.2 ng/dL STANDARD_DEVIATION 75.19 | 130.0 ng/dL STANDARD_DEVIATION 65.96 |
| Cortisol | 14.54 ug/dL STANDARD_DEVIATION 5.879 | 13.44 ug/dL STANDARD_DEVIATION 4.847 | 16.41 ug/dL STANDARD_DEVIATION 7.206 |
| Dehydroepiandrosterone sulfate (DHEAS) | 364.8 ug/dL STANDARD_DEVIATION 96.65 | 351.3 ug/dL STANDARD_DEVIATION 90.53 | 387.8 ug/dL STANDARD_DEVIATION 107.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 15 Participants | 9 Participants |
| Sex: Female, Male Female | 27 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Testosterone | 61.0 ng/dL STANDARD_DEVIATION 23.43 | 61.0 ng/dL STANDARD_DEVIATION 21.97 | 61.1 ng/dL STANDARD_DEVIATION 26.97 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 10 |
| other Total, other adverse events | 13 / 17 | 9 / 10 |
| serious Total, serious adverse events | 1 / 17 | 0 / 10 |
Outcome results
Primary
Change in DHEAS
To evaluate the effect of tildacerfont in changing (reducing) DHEAS in subjects with PCOS and elevated adrenal androgens
Time frame: 12 weeks (assessed at Baseline, Weeks 4, 8 and 12)
Population: Analysis of Change from Baseline in DHEAS (μg/dL) at Week 12, Modified Intent-to-Treat Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Tildacerfont | Change in DHEAS | -22.93 ug/dL | Standard Deviation 67.6 |
| Placebo Control Arm | Change in DHEAS | -7.56 ug/dL | Standard Deviation 16 |
Secondary
Normalization of DHEAS
Number of subjects with DHEAS =/\< upper limit of normal for DHEAS
Time frame: 12 weeks (assessed at Baseline, Weeks 4, 8 and 12)
Population: Number of subjects with DHEAS =/\< upper limit of normal for DHEAS at Week 12, Modified Intent-to-treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Tildacerfont | Normalization of DHEAS | 8 Participants |
| Placebo Control Arm | Normalization of DHEAS | 6 Participants |
Secondary
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
Time frame: 12 weeks (assessed at Baseline, Weeks 4, 8 and 12)
Population: All subjects who received at least 1 dose of placebo or tildacerfont; Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Tildacerfont | Number of Subjects With TEAE as Assessed by CTCAE Version 5 | 13 Participants |
| Placebo Control Arm | Number of Subjects With TEAE as Assessed by CTCAE Version 5 | 9 Participants |
Secondary
Reduction in DHEAS
Number of subjects with \>/=30% change from baseline in DHEAS
Time frame: 12 weeks (assessed at Baseline, Weeks 4, 8 and 12)
Population: Number of subjects with a \>/=30% change from Baseline in DHEAS (μg/dL) at Week 12, Modified Intent-to-Treat Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment With Tildacerfont | Reduction in DHEAS | 1 Participants |
| Placebo Control Arm | Reduction in DHEAS | 1 Participants |