Polycystic Ovary Syndrome (PCOS), Female Endocrine Disorder
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics, endocrinopathies, PCOS, female, hormone, LH
Brief summary
To assess the effects of AZD4901 when given in multiple doses to females with Polycystic Ovary Syndrome
Interventions
DRUGPlacebo to match AZD4901
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
DRUGAZD4901 (oral)
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Female patients between the ages of 18 to 45 years (inclusive). Suitable veins for cannulation or repeated venipuncture. Body mass index (BMI) between 18 and 40 kg/m2 (inclusive). A diagnosis of polycystic ovary disease. Amenorrhea or oligomenorrhea (defined as ≤ 6 menses per year). Negative serum pregnancy test at screening. Negative urine pregnancy test before randomisation. Not be breast-feeding. Not have been pregnant within the 6 months prior to screening.
Exclusion criteria
Perimenopausal or reached natural menopause, defined as FSH \> 10 IU/L. Menstruated within the month prior to the baseline visit. Hysterectomy or bilateral oophorectomy or both. Clinically relevant disease and abnormalities (past or present), and in particular causes of abnormal vaginal bleeding. Withdrawals from oral contraceptives if their LH levels are below 3 IU/L when retested within 7 ± 1 days of the baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 | Day 7 | Change-from-baseline of luteinising hormone area under the concentration-time curve from time zero to 8 hours postdose \[AUC(0-8)\] at Day 7 |
Countries
Germany, United Kingdom, United States
Participant flow
Recruitment details
67 patients were recruited to the study, of which 65 received doses of AZD4901 between 20 mg qd and 40 mg bid or placebo. Two patients were excluded due to poor venous access
Participants by arm
| Arm | Count |
|---|---|
| Placebo Two matching placebo tablets for both the morning and evening doses | 16 |
| 20 mg AZD4901 Once Daily One 20-mg AZD4901 tablet and 1 placebo tablet for the morning dose and 2 placebo tablets for the evening dose | 15 |
| 20 mg AZD4901 Twice Daily One 20-mg AZD4901 tablet and 1 placebo tablet for both the morning and evening doses | 17 |
| 40 mg AZD4901 Twice Daily Two 20-mg AZD4901 tablets for both the morning and evening doses | 17 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Dose administration non-compliance | 0 | 0 | 0 | 1 |
| Overall Study | Patient met exclusion criterion 16. | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27 Years STANDARD_DEVIATION 3 | 29 Years STANDARD_DEVIATION 6 | 27 Years STANDARD_DEVIATION 6 | 28 Years STANDARD_DEVIATION 6 | 28 Years STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 17 Participants | 17 Participants | 65 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 15 | 13 / 17 | 5 / 17 | 6 / 16 |
| serious Total, serious adverse events | 0 / 15 | 1 / 17 | 0 / 17 | 0 / 16 |
Outcome results
Primary
Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7
Change-from-baseline of luteinising hormone area under the concentration-time curve from time zero to 8 hours postdose \[AUC(0-8)\] at Day 7
Time frame: Day 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 | 1.118 Ratio |
| 20 mg AZD4901 qd | Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 | 0.9729 Ratio |
| 20 mg AZD4901 Bid | Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 | 0.8804 Ratio |
| 40 mg AZD4901 Bid | Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 | 0.5364 Ratio |
Comparison: The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100%95% CI: [58.52, 129.47]
Comparison: The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100%95% CI: [53.41, 116.16]
Comparison: The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100%95% CI: [32.73, 70.36]