Polycystic Ovary Syndrome
Conditions
Keywords
Polycystic Ovary Syndrome, Hormone, Elagolix
Brief summary
This study will assess the potential impact of elagolix on disordered pituitary and ovarian hormones in women with polycystic ovary syndrome (PCOS).
Detailed description
This is a phase 2, multicenter, double-blind (sponsor-unblinded), randomized, placebo-controlled study to assess the safety and efficacy of elagolix in women with PCOS. PCOS is one of the most common hormonal disorders in women of reproductive age, yet few treatment options are available. This study will help determine if elagolix can impact disordered hormonal dynamics in women with PCOS and at what dosage.
Interventions
DRUGElagolix
Capsule administered orally
DRUGPlacebo
Capsule administered orally
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Participants with clinical diagnosis of PCOS. * Participants with a body mass index (BMI) of 18.5 to 38 kg/m\^2 at time of Screening.
Exclusion criteria
* Participants with newly diagnosed medical condition requiring intervention that has not been stabilized at least 30 days prior to Baseline. * Participants with a significant medical condition that require intervention during the course of study participation (such as anticipated major elective surgery). * Participants with an unstable medical condition (including, but not limited to, uncontrolled hypertension, epilepsy requiring anti-epileptic medicine, unstable angina, confirmed inflammatory bowel disease, hyperprolactinemia, clinically significant infection or injury).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Menstrual Cycle Responders | Week 0 (Baseline) to Week 24 (Month 6) | A participant was considered a menstrual cycle responder if she has at least 2 normal menstrual cycles during the final 4 months of the treatment period. In addition, a participant was considered a complete menstrual cycle responder if she has normal menstrual cycles beginning at or before Month 3 that are maintained through Month 6 during the treatment period. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | Week 0 (Baseline), Week 1: before the morning dose (0 hour) and at 0.5 (± 5 minutes), 1 (± 5 minutes), 1.5 (± 5 minutes), 2 (± 15 minutes), 2.5 (± 15 minutes), 3 (± 15 minutes), 3.5 (± 15 minutes), and 4 (± 15 minutes) hours after dosing. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Participants were randomized 2:2:2:2:2:3 to the following treatments: 25 mg twice daily (BID), 50 mg once daily (QD), 75 mg BID, 150 mg QD, 300 mg QD, or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo taken orally BID | 26 |
| Elagolix 25 mg BID Elagolix 25 mg taken orally BID plus placebo | 18 |
| Elagolix 50 mg QD Elagolix 50 mg taken orally QD plus placebo | 17 |
| Elagolix 75 mg BID Elagolix 75 mg taken orally BID plus placebo | 17 |
| Elagolix 150 mg QD Elagolix 150 mg taken orally QD plus placebo | 18 |
| Elagolix 300 mg QD Elagolix 300 mg taken orally QD plus placebo | 18 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Did Not Receive Any Study Drug | 1 | 0 | 1 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 3 | 2 | 3 |
| Overall Study | Non-Compliance With Study Procedures | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other, Not Specified | 12 | 10 | 10 | 5 | 9 | 6 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 0 | 3 | 3 | 2 |
Baseline characteristics
| Characteristic | Elagolix 25 mg BID | Elagolix 50 mg QD | Elagolix 75 mg BID | Elagolix 150 mg QD | Elagolix 300 mg QD | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 25.3 years STANDARD_DEVIATION 5.19 | 27.6 years STANDARD_DEVIATION 4.85 | 26.9 years STANDARD_DEVIATION 3.27 | 25.1 years STANDARD_DEVIATION 4.19 | 26.1 years STANDARD_DEVIATION 4.35 | 27.8 years STANDARD_DEVIATION 4.6 | 26.5 years STANDARD_DEVIATION 4.5 |
| Body Mass Index (BMI) < 30 kg/m^2 | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 8 Participants | 33 Participants |
| Body Mass Index (BMI) ≥ 30 kg/m^2 | 13 Participants | 12 Participants | 12 Participants | 13 Participants | 13 Participants | 18 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 11 Participants | 14 Participants | 14 Participants | 14 Participants | 21 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 5 Participants | 7 Participants | 4 Participants | 6 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 16 Participants | 12 Participants | 11 Participants | 14 Participants | 19 Participants | 85 Participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 17 Participants | 18 Participants | 18 Participants | 26 Participants | 114 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 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 | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 18 | 0 / 17 | 0 / 17 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 10 / 26 | 9 / 18 | 8 / 17 | 6 / 17 | 11 / 18 | 10 / 18 |
| serious Total, serious adverse events | 0 / 26 | 1 / 18 | 0 / 17 | 0 / 17 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Percentage of Menstrual Cycle Responders
A participant was considered a menstrual cycle responder if she has at least 2 normal menstrual cycles during the final 4 months of the treatment period. In addition, a participant was considered a complete menstrual cycle responder if she has normal menstrual cycles beginning at or before Month 3 that are maintained through Month 6 during the treatment period.
Time frame: Week 0 (Baseline) to Week 24 (Month 6)
Population: Full Analysis Set: all randomly assigned participants who have received at least one dose of study drug in this study. Based on observed cases only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Menstrual Cycle Responders | 7.7 percentage of participants |
| Elagolix 25 mg BID | Percentage of Menstrual Cycle Responders | 0 percentage of participants |
| Elagolix 50 mg QD | Percentage of Menstrual Cycle Responders | 0 percentage of participants |
| Elagolix 75 mg BID | Percentage of Menstrual Cycle Responders | 0 percentage of participants |
| Elagolix 150 mg QD | Percentage of Menstrual Cycle Responders | 0 percentage of participants |
| Elagolix 300 mg QD | Percentage of Menstrual Cycle Responders | 5.6 percentage of participants |
Comparison: Across the strata, 90% confidence interval (CI) for adjusted difference and p-value were calculated according to the Cochran-Mantel-Haenszel (CMH) test adjusted for strata (Baseline FG score \[\< 8, ≥ 8\], and baseline normal/obese status \[BMI \< 30, ≥ 30\]) for the comparison of between each elagolix group and placebo. If zero frequency occurred, the zero count was replaced by 0.1 to prevent dividing by zero.p-value: 0.390% CI: [-15.38, 3.49]Cochran-Mantel-Haenszel
Comparison: Across the strata, 90% CI for adjusted difference and p-value were calculated according to the CMH test adjusted for strata (Baseline FG score \[\< 8, ≥ 8\], and baseline normal/obese status \[BMI \< 30, ≥ 30\]) for the comparison of between each elagolix group and placebo. If zero frequency occurred, the zero count was replaced by 0.1 to prevent dividing by zero.p-value: 0.3290% CI: [-15.65, 3.86]Cochran-Mantel-Haenszel
Comparison: Across the strata, 90% CI for adjusted difference and p-value were calculated according to the CMH test adjusted for strata (Baseline FG score \[\< 8, ≥ 8\], and baseline normal/obese status \[BMI \< 30, ≥ 30\]) for the comparison of between each elagolix group and placebo. If zero frequency occurred, the zero count was replaced by 0.1 to prevent dividing by zero.p-value: 0.31590% CI: [-14.87, 3.59]Cochran-Mantel-Haenszel
Comparison: Across the strata, 90% CI for adjusted difference and p-value were calculated according to the CMH test adjusted for strata (Baseline FG score \[\< 8, ≥ 8\], and baseline normal/obese status \[BMI \< 30, ≥ 30\]) for the comparison of between each elagolix group and placebo. If zero frequency occurred, the zero count was replaced by 0.1 to prevent dividing by zero.p-value: 0.26590% CI: [-16.63, 3.19]Cochran-Mantel-Haenszel
Comparison: Across the strata, 90% CI for adjusted difference and p-value were calculated according to the CMH test adjusted for strata (Baseline FG score \[\< 8, ≥ 8\], and baseline normal/obese status \[BMI \< 30, ≥ 30\]) for the comparison of between each elagolix group and placebo. If zero frequency occurred, the zero count was replaced by 0.1 to prevent dividing by zero.p-value: 0.91490% CI: [-13.1, 11.48]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1
Time frame: Week 0 (Baseline), Week 1: before the morning dose (0 hour) and at 0.5 (± 5 minutes), 1 (± 5 minutes), 1.5 (± 5 minutes), 2 (± 15 minutes), 2.5 (± 15 minutes), 3 (± 15 minutes), 3.5 (± 15 minutes), and 4 (± 15 minutes) hours after dosing.
Population: Full Analysis Set: all randomly assigned participants who have received at least one dose of study drug in this study. Participants with an assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -1.82 (IU/L)*hr | Standard Error 2.292 |
| Elagolix 25 mg BID | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -7.75 (IU/L)*hr | Standard Error 2.867 |
| Elagolix 50 mg QD | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -10.65 (IU/L)*hr | Standard Error 2.861 |
| Elagolix 75 mg BID | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -17.92 (IU/L)*hr | Standard Error 2.692 |
| Elagolix 150 mg QD | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -7.97 (IU/L)*hr | Standard Error 3.112 |
| Elagolix 300 mg QD | Change From Baseline in Area Under the Luteinizing Hormone (LH) Serum Concentration-time Curve (AUC) at Week 1 | -13.54 (IU/L)*hr | Standard Error 2.763 |
Comparison: P-value is from mixed-effect model repeated measure (MMRM) with the fixed categorical effects of treatment, visit, treatment-by-visit interaction, baseline FG score (\< 8, ≥ 8), and baseline normal/obese status (BMI \< 30, ≥ 30), participant as a random effect, and the continuous fixed covariate of baseline measurement. Model is based on unstructured variance covariance structure.p-value: 0.08790% CI: [-11.628, -0.231]MMRM
Comparison: P-value is from MMRM with the fixed categorical effects of treatment, visit, treatment-by-visit interaction, baseline FG score (\< 8, ≥ 8), and baseline normal/obese status (BMI \< 30, ≥ 30), participant as a random effect, and the continuous fixed covariate of baseline measurement. Model is based on unstructured variance covariance structure.p-value: 0.01290% CI: [-14.533, -3.118]MMRM
Comparison: P-value is from MMRM with the fixed categorical effects of treatment, visit, treatment-by-visit interaction, baseline FG score (\< 8, ≥ 8), and baseline normal/obese status (BMI \< 30, ≥ 30), participant as a random effect, and the continuous fixed covariate of baseline measurement. Model is based on unstructured variance covariance structure.p-value: <0.00190% CI: [-21.673, -10.519]MMRM
Comparison: P-value is from MMRM with the fixed categorical effects of treatment, visit, treatment-by-visit interaction, baseline FG score (\< 8, ≥ 8), and baseline normal/obese status (BMI \< 30, ≥ 30), participant as a random effect, and the continuous fixed covariate of baseline measurement. Model is based on unstructured variance covariance structure.p-value: 0.09190% CI: [-12.116, -0.176]MMRM
Comparison: P-value is from MMRM with the fixed categorical effects of treatment, visit, treatment-by-visit interaction, baseline FG score (\< 8, ≥ 8), and baseline normal/obese status (BMI \< 30, ≥ 30), participant as a random effect, and the continuous fixed covariate of baseline measurement. Model is based on unstructured variance covariance structure.p-value: <0.00190% CI: [-17.418, -6.016]MMRM