Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic ovary syndrome, PCOS, hyperandrogenism, insulin resistance, overweight, obesity
Brief summary
The purpose of the study was to evaluate whether LIK066 can be developed for the treatment of polycystic ovary syndrome (PCOS) in overweight and obese women.
Interventions
DRUGLIK066
LIK066 tablets for oral administration
DRUGPlacebo
Placebo tablets matching LIK066 tablets, for oral administration
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * PCOS (diagnosed as clinical or biochemical hyperandrogenism, amenorrhea or oligomenorrhea and exclusion of other causes of hyperandrogenism. * Overweight/obese female subjects with BMI of 28 - 45 kg/m\^2, inclusive, and stable weight +/- 3 kg over previous 3 months * Subjects must use non-hormonal methods of contraception during the study. Key
Exclusion criteria
* Subjects with exogenous causes of hirsutism * Menstruation in the 30 days prior to screening or treatment * Pregnant or nursing (lactating) women * Use of prohibited medications * Preexisting medical condition which may significantly alter the absorption, metabolism, or excretion of the study drug, or which may jeopardize the subject in case of participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Average Morning Fasting Free Testosterone Blood Concentrations From Baseline | Baseline, Day 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Follicle Stimulating Hormone (FSH) at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Androstenedione at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Luteinizing Hormone (LH) at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Dehydroepiandrostenedione Sulfate (DHEAS) at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Total Testosterone, at Day 15 | Baseline, Day 15 | — |
| Change From Baseline in Free Androgen Index (FAI), at Day 15 | Baseline, Day 15 | Free Androgen Index (FAI) is a ratio used to determine abnormal androgen status in humans. The ratio is the total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by 100. FAI has no units. |
| Change From Baseline in Dehydroepiandrostenedione (DHEA) at Day 15 | Baseline, Day 15 | — |
Countries
Germany, United States
Participant flow
Recruitment details
This study was conducted in 5 centers in 2 countries: Germany (3), and USA (2).
Pre-assignment details
Participants were randomized in the ratio of 1:1 to receive either LIK066 50 mg tid or placebo for 14 days and morning dose on Day 15.
Participants by arm
| Arm | Count |
|---|---|
| LIK066 LIK066 tablets received three times daily; before breakfast, lunch and dinner for 14 days and once on day 15 morning before meal test | 15 |
| Placebo Placebo tablets received three times daily; before breakfast, lunch and dinner for 14 days and once on day 15 morning before meal test | 14 |
| Total | 29 |
Baseline characteristics
| Characteristic | LIK066 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 26.1 Years STANDARD_DEVIATION 4.76 | 29.1 Years STANDARD_DEVIATION 5.66 | 27.6 Years STANDARD_DEVIATION 5.34 |
| Average fasting free testosterone | 0.037 nmol/L STANDARD_DEVIATION 0.0163 | 0.032 nmol/L STANDARD_DEVIATION 0.0086 | 0.034 nmol/L STANDARD_DEVIATION 0.0132 |
| Average fasting total testosterone | 1.98 nmol/L STANDARD_DEVIATION 0.841 | 2.07 nmol/L STANDARD_DEVIATION 0.608 | 2.02 nmol/L STANDARD_DEVIATION 0.724 |
| Free androgen Index | 12.4 ratio STANDARD_DEVIATION 6.65 | 9.0 ratio STANDARD_DEVIATION 2.77 | 10.7 ratio STANDARD_DEVIATION 5.27 |
| Race/Ethnicity, Customized White | 15 Participants | 14 Participants | 29 Participants |
| Sex/Gender, Customized Female | 15 Participants | 14 Participants | 29 Participants |
| Sex hormone binding globulin (SHBG) | 18.3 nmol/L STANDARD_DEVIATION 7.72 | 24.6 nmol/L STANDARD_DEVIATION 10.51 | 21.4 nmol/L STANDARD_DEVIATION 9.58 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 15 / 15 | 10 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 |
Outcome results
Primary
Change in Average Morning Fasting Free Testosterone Blood Concentrations From Baseline
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change in Average Morning Fasting Free Testosterone Blood Concentrations From Baseline | 0.91 nmol/L |
| Placebo | Change in Average Morning Fasting Free Testosterone Blood Concentrations From Baseline | 1.03 nmol/L |
p-value: 0.35390% CI: [0.7, 1.11]t-test, 2 sided
Secondary
Change From Baseline in Androstenedione at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Androstenedione at Day 15 | 0.85 nmol/L |
| Placebo | Change From Baseline in Androstenedione at Day 15 | 1.03 nmol/L |
p-value: 0.08990% CI: [0.68, 0.99]t-test, 2 sided
Secondary
Change From Baseline in Dehydroepiandrostenedione (DHEA) at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Dehydroepiandrostenedione (DHEA) at Day 15 | 0.75 nmol/L |
| Placebo | Change From Baseline in Dehydroepiandrostenedione (DHEA) at Day 15 | 1.09 nmol/L |
p-value: 0.10990% CI: [0.48, 1.01]t-test, 2 sided
Secondary
Change From Baseline in Dehydroepiandrostenedione Sulfate (DHEAS) at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Dehydroepiandrostenedione Sulfate (DHEAS) at Day 15 | 0.84 umol/L |
| Placebo | Change From Baseline in Dehydroepiandrostenedione Sulfate (DHEAS) at Day 15 | 1.10 umol/L |
p-value: 0.00890% CI: [0.65, 0.89]t-test, 2 sided
Secondary
Change From Baseline in Follicle Stimulating Hormone (FSH) at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Follicle Stimulating Hormone (FSH) at Day 15 | 1.13 U/L |
| Placebo | Change From Baseline in Follicle Stimulating Hormone (FSH) at Day 15 | 0.89 U/L |
p-value: 0.24990% CI: [0.9, 1.78]t-test, 2 sided
Secondary
Change From Baseline in Free Androgen Index (FAI), at Day 15
Free Androgen Index (FAI) is a ratio used to determine abnormal androgen status in humans. The ratio is the total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by 100. FAI has no units.
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Free Androgen Index (FAI), at Day 15 | 0.85 Ratio |
| Placebo | Change From Baseline in Free Androgen Index (FAI), at Day 15 | 1.07 Ratio |
p-value: 0.20490% CI: [0.58, 1.08]t-test, 2 sided
Secondary
Change From Baseline in Luteinizing Hormone (LH) at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Luteinizing Hormone (LH) at Day 15 | 1.37 U/L |
| Placebo | Change From Baseline in Luteinizing Hormone (LH) at Day 15 | 1.10 U/L |
p-value: 0.21890% CI: [0.92, 1.68]t-test, 2 sided
Secondary
Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Day 15 | 1.06 nmol/L |
| Placebo | Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Day 15 | 0.93 nmol/L |
p-value: 0.17390% CI: [0.97, 1.36]t-test, 2 sided
Secondary
Change From Baseline in Total Testosterone, at Day 15
Time frame: Baseline, Day 15
Population: Pharmacodynamic (PD) analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LIK066 | Change From Baseline in Total Testosterone, at Day 15 | 0.95 nmol/L |
| Placebo | Change From Baseline in Total Testosterone, at Day 15 | 1.04 nmol/L |
p-value: 0.3490% CI: [0.77, 1.07]t-test, 2 sided