Trial Outcomes & Findings for Combined Letrozole and Clomid in Women With Infertility and PCOS (NCT NCT02802865)

NCT ID: NCT02802865

Last Updated: 2019-09-27

Results Overview

Ovulation: mid-luteal progesterone \> /=3 ng/mL. No ovulation: mid-luteal progesterone \<3ng/mL.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 70 participants
• Primary outcome timeframe: 7 days following LH surge or at cycle day 21 if no LH surge was detected
• Results posted on: 2019-09-27

Participant Flow

Participant milestones

Measure	Letrozole Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Overall Study STARTED	35	35
Overall Study COMPLETED	34	33
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Letrozole Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Overall Study Pregnancy	1	1
Overall Study Ineliegible due to tuberculosis	0	1

Baseline Characteristics

Participants who had previously used Letrozole

Baseline characteristics by cohort

Measure	Letrozole n=35 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=35 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole	Total n=70 Participants Total of all reporting groups
Age, Continuous	31 years STANDARD_DEVIATION 3.9 • n=35 Participants	30 years STANDARD_DEVIATION 4.4 • n=35 Participants	31 years STANDARD_DEVIATION 4.1 • n=70 Participants
Sex: Female, Male Female	35 Participants n=35 Participants	35 Participants n=35 Participants	70 Participants n=70 Participants
Sex: Female, Male Male	0 Participants n=35 Participants	0 Participants n=35 Participants	0 Participants n=70 Participants
Race/Ethnicity, Customized Race/Ethnicity · White	29 Participants n=35 Participants	30 Participants n=35 Participants	59 Participants n=70 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black	2 Participants n=35 Participants	1 Participants n=35 Participants	3 Participants n=70 Participants
Race/Ethnicity, Customized Race/Ethnicity · Asian	1 Participants n=35 Participants	1 Participants n=35 Participants	2 Participants n=70 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic or Latino	2 Participants n=35 Participants	2 Participants n=35 Participants	4 Participants n=70 Participants
Race/Ethnicity, Customized Race/Ethnicity · More than 1 race	1 Participants n=35 Participants	1 Participants n=35 Participants	2 Participants n=70 Participants
Region of Enrollment United States	35 participants n=35 Participants	35 participants n=35 Participants	70 participants n=70 Participants
BMI	33 kg/m^2 STANDARD_DEVIATION 8.7 • n=35 Participants	34 kg/m^2 STANDARD_DEVIATION 7.0 • n=35 Participants	33 kg/m^2 STANDARD_DEVIATION 7.8 • n=70 Participants
Weight	94 kg STANDARD_DEVIATION 29.6 • n=35 Participants	94 kg STANDARD_DEVIATION 22.5 • n=35 Participants	94 kg STANDARD_DEVIATION 26.1 • n=70 Participants
Insurance Coverage Full coverage	10 Participants n=35 Participants	15 Participants n=35 Participants	25 Participants n=70 Participants
Insurance Coverage Partial coverage	9 Participants n=35 Participants	10 Participants n=35 Participants	19 Participants n=70 Participants
Insurance Coverage No coverage/unsure	16 Participants n=35 Participants	10 Participants n=35 Participants	26 Participants n=70 Participants
PCOS Diagnsosis Polycystic ovaries according to modified Rotterdam	35 Participants n=35 Participants	32 Participants n=35 Participants	67 Participants n=70 Participants
PCOS Diagnsosis Hyperandrogenism	20 Participants n=35 Participants	21 Participants n=35 Participants	41 Participants n=70 Participants
PCOS Diagnsosis Oligomenorrhea	34 Participants n=35 Participants	33 Participants n=35 Participants	67 Participants n=70 Participants
Previous Live Birth	14 Participants n=35 Participants	11 Participants n=35 Participants	25 Participants n=70 Participants
Duration of Time Attempting to Conceive	30 months STANDARD_DEVIATION 29.6 • n=35 Participants	28 months STANDARD_DEVIATION 18.5 • n=35 Participants	29 months STANDARD_DEVIATION 24.5 • n=70 Participants
Previous use of Letrozole	10 Participants n=35 Participants	17 Participants n=35 Participants	27 Participants n=70 Participants
Max dose of Letrzole	5 mg n=10 Participants • Participants who had previously used Letrozole	5 mg n=17 Participants • Participants who had previously used Letrozole	5 mg n=27 Participants • Participants who had previously used Letrozole
Ovulation on max dose of Letrozole	4 Participants n=10 Participants • Participants who had previously used Letrozole.	7 Participants n=16 Participants • Participants who had previously used Letrozole.	11 Participants n=26 Participants • Participants who had previously used Letrozole.
Letrozole use >6 mo before	6 Participants n=10 Participants • Participants who had previously used Letrozole.	10 Participants n=16 Participants • Participants who had previously used Letrozole.	16 Participants n=26 Participants • Participants who had previously used Letrozole.
Previous use of Clomiphene	17 Participants n=35 Participants	23 Participants n=35 Participants	40 Participants n=70 Participants
Max dose of Clomiphene	150 mg n=17 Participants • Participants who had previously used Clomiphene.	150 mg n=23 Participants • Participants who had previously used Clomiphene.	150 mg n=40 Participants • Participants who had previously used Clomiphene.
Ovulation on max dose of Clomiphene	9 Participants n=16 Participants • Participants who had previously used Clomiphene.	8 Participants n=23 Participants • Participants who had previously used Clomiphene.	17 Participants n=39 Participants • Participants who had previously used Clomiphene.
Clomiphene use >6mo before	7 Participants n=16 Participants • Participants who had previously used Clomiphene	14 Participants n=23 Participants • Participants who had previously used Clomiphene	21 Participants n=39 Participants • Participants who had previously used Clomiphene
Previous use of both Letrozole and Clomiphene	8 Participants n=35 Participants	14 Participants n=35 Participants	22 Participants n=70 Participants
Resistance to both Letrozole and Clomid	4 Participants n=8 Participants • Participants who had previously used both Letrozole and Clomiphene.	7 Participants n=14 Participants • Participants who had previously used both Letrozole and Clomiphene.	11 Participants n=22 Participants • Participants who had previously used both Letrozole and Clomiphene.
Metformin Use Current Use	14 Participants n=35 Participants	15 Participants n=35 Participants	29 Participants n=70 Participants
Metformin Use Previous Use/Not Current	6 Participants n=35 Participants	10 Participants n=35 Participants	16 Participants n=70 Participants
Metformin Use Never Used	15 Participants n=35 Participants	10 Participants n=35 Participants	25 Participants n=70 Participants
HbA1c	5.3 mmol/mol STANDARD_DEVIATION 0.47 • n=23 Participants • Participants with prior HbA1c available at baseline.	5.3 mmol/mol STANDARD_DEVIATION 0.73 • n=23 Participants • Participants with prior HbA1c available at baseline.	5.3 mmol/mol STANDARD_DEVIATION 0.61 • n=46 Participants • Participants with prior HbA1c available at baseline.
Fasting Blood Glucose	95 mg/dL STANDARD_DEVIATION 6.7 • n=6 Participants • Participants who had prior 2-h GTT available.	90 mg/dL STANDARD_DEVIATION 10.6 • n=9 Participants • Participants who had prior 2-h GTT available.	93 mg/dL STANDARD_DEVIATION 9.3 • n=15 Participants • Participants who had prior 2-h GTT available.
2-hr GTT	103 mg/dL STANDARD_DEVIATION 18.5 • n=6 Participants • Participants who had prior 2-h GTT available.	114 mg/dL STANDARD_DEVIATION 23.0 • n=9 Participants • Participants who had prior 2-h GTT available.	110 mg/dL STANDARD_DEVIATION 21.2 • n=15 Participants • Participants who had prior 2-h GTT available.
Current tobacco use	1 Participants n=35 Participants	3 Participants n=35 Participants	4 Participants n=70 Participants

PRIMARY outcome

Timeframe: 7 days following LH surge or at cycle day 21 if no LH surge was detected

Ovulation: mid-luteal progesterone > /=3 ng/mL. No ovulation: mid-luteal progesterone <3ng/mL.

Outcome measures

Measure	Letrozole n=35 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=35 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level	15 Participants	27 Participants

SECONDARY outcome

Timeframe: Cycle day 12-14

Number of follicles measuring > 10mm on ultrasound

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Number of Developing Follicles	0 follicles Interval 0.0 to 1.0	1 follicles Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: Cycle day 12-14

Size of largest follicle on ultrasound

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Size of Largest Developing Follicle	10 mm Interval 8.75 to 15.25	16 mm Interval 10.0 to 19.0

SECONDARY outcome

Timeframe: Cycle day 12-14

Thickness of endometrial lining assessed by ultrasound

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Endometrial Thickness	6.2 mm Standard Deviation 2.2	8.3 mm Standard Deviation 3.6

SECONDARY outcome

Timeframe: 5 weeks after treatment

Conception: a positive serum or urinary test of hCG; No conception: Neither a positive serum or urinary test of hCG

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Conception	3 Participants	4 Participants

SECONDARY outcome

Timeframe: 6-7 weeks after treatment

Clinical Pregnancy: an intrauterine pregnancy with fetal heart motion determined by ultrasonography; No Clinical Pregnancy: no intrauterine pregnancy with fetal heart motion determined by ultrasonography

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Clinical Pregnancy	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 9-10 months after treatment

Multiple Gestation: an intrauterine pregnancy with multiple fetal heart rates determined by ultrasonography; No Multiple Gestation: either no intrauterine pregnancy, or an intrauterine pregnancy with a single fetal heart rate determined by ultrasonography

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Multiple Gestation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 9-10 months after treatment

Live Birth: delivery of a live infant; No Live Birth: no delivery of a live infant

Outcome measures

Measure	Letrozole n=34 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=33 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Live Birth	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 9-10 months after treatment

Population: Participants who conceived

Pregnancy Loss: any pregnancy loss including biochemical pregnancy, ectopic pregnancy, and miscarriage; No Pregnancy Loss: no pregnancy loss including biochemical pregnancy, ectopic pregnancy, or miscarriage.

Outcome measures

Measure	Letrozole n=3 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=4 Participants Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Pregnancy Loss	2 Participants	1 Participants

Adverse Events

Letrozole

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Letrozole + Clomiphene

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Letrozole n=33 participants at risk Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=32 participants at risk Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Hepatobiliary disorders Gallstones	3.0% 1/33 • Number of events 1 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	0.00% 0/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Infections and infestations Appendicitis	0.00% 0/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Number of events 1 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.

Other adverse events

Measure	Letrozole n=33 participants at risk Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Letrozole	Letrozole + Clomiphene n=32 participants at risk Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Clomiphene Letrozole
Nervous system disorders Headache	39.4% 13/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	28.1% 9/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Reproductive system and breast disorders Hot flashes	12.1% 4/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	31.2% 10/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Gastrointestinal disorders Abdominal bloating	6.1% 2/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	0.00% 0/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Gastrointestinal disorders Nausea	9.1% 3/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	9.4% 3/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Psychiatric disorders Mood changes	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	12.5% 4/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
General disorders Fatigue	21.2% 7/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	12.5% 4/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Nervous system disorders Dizziness	6.1% 2/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Reproductive system and breast disorders Breast Discomfort	9.1% 3/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	6.2% 2/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Gastrointestinal disorders Diarrhea	6.1% 2/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Skin and subcutaneous tissue disorders Night sweats	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	6.2% 2/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Psychiatric disorders Sleep disturbances including insomnia	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	6.2% 2/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
General disorders Abdominal pain including cramps	18.2% 6/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	18.8% 6/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Infections and infestations Urinary tract infection	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Skin and subcutaneous tissue disorders Pilonidal cyst	3.0% 1/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	0.00% 0/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.
Pregnancy, puerperium and perinatal conditions Echogenic bowel and small head on ultrasound	0.00% 0/33 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.	3.1% 1/32 • Participants were followed for approximately 1 month (1 menstrual cycle) for adverse events related to treatment medication. Participants who became pregnant during the treatment cycle were followed for up to approximately 9 months through the resolution of their pregnancy for adverse events during the pregnancy resulting from the study medication. Participants were provided with a calendar log to keep track of medication side-effects each day of their treatment cycle. Adverse events in pregnancy were tracked through chart abstraction and participant self reporting.

Additional Information

Dr. Rachel Mejia

University of Iowa

Phone: 319-356-3143

Email: rachel-mejia@uiowa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place