Anovulation
Conditions
Brief summary
The purpose of this study is to investigate and compare the safety and efficacy of various doses of the aromatase inhibitor (anastrozole) versus clomiphene citrate in stimulating follicular growth and ovulation in infertile women with ovulatory dysfunction.
Interventions
Subjects will be administered orally with 50 mg of clomiphene citrate once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month).
DRUGClomiphene Citrate 100 mg
Subjects will be administered orally with 100 mg of clomiphene citrate once daily for 5 days in Cycle 2 and 3 (each cycle = approximately 1 month).
DRUGAnastrozole 1 mg
Subjects will be administered orally with 1 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month).
DRUGAnastrozole 5 mg
Subjects will be administered orally with 5 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month).
DRUGAnastrozole 10 mg
Subjects will be administered orally with 10 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month).
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-40 years * Ovulatory dysfunction characterized by irregular and/or extended cycles * Non-smoker
Exclusion criteria
* No previous gonadotropin treatment * No more than 6 previous clomiphene treatment cycles
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ovulation Rate in Cycle 1 | Up to 1 month | Ovulation rate was defined as the percentage of subjects who ovulated (mid-luteal Progesteron \[P4\] level greater than or equal to \[\>=\] 10 nanogram per milliliter \[ng/mL\] and/or pregnancy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Clinical Pregnancy in Cycle 1 | Up to 1 month | Clinical pregnancy was defined as the existence of at least one ultrasonographically confirmed gestational sac in the uterus with fetal heart activity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clomiphene Citrate 50 mg Subjects were administered orally with 50 mg of clomiphene citrate once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month). Subjects in this arm were re-randomized at the start of Cycle 2 and Cycle 3 and either continued receiving Clomiphene Citrate 50 mg or moved to Clomiphene Citrate 100 mg arm. | 77 |
| Anastrozole 1 mg Subjects were administered orally with 1 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month). Subjects in this arm were re-randomized at the start of Cycle 2 and Cycle 3 and either continued receiving Anastrozole 1 mg or moved to Anastrozole 10 mg arm. | 79 |
| Anastrozole 5 mg Subjects were administered orally with 5 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month). Subjects in this arm were re-randomized at the start of Cycle 2 and Cycle 3 and either continued receiving Anastrozole 5 mg or moved to Anastrozole 10 mg arm. | 76 |
| Anastrozole 10 mg Subjects were administered orally with 10 mg of anastrozole once daily for 5 days in Cycle 1, 2 and 3 (each cycle = approximately 1 month). Some of the subjects from Anastrozole 1 mg and 5 mg arms were re-randomized at the start of Cycle 2 and Cycle 3 to Anastrozole 10 mg arm. | 39 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Cycle 1 (1 Month) | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Cycle 1 (1 Month) | Discontinued Before Start of Cycle 2 | 15 | 0 | 5 | 8 | 5 |
| Cycle 1 (1 Month) | Lack of Efficacy | 4 | 0 | 8 | 5 | 8 |
| Cycle 1 (1 Month) | Lost to Follow-up | 1 | 0 | 2 | 2 | 1 |
| Cycle 1 (1 Month) | Non Resolving Cyst > 25mm | 0 | 0 | 0 | 0 | 1 |
| Cycle 1 (1 Month) | Other | 3 | 0 | 2 | 2 | 7 |
| Cycle 1 (1 Month) | Pregnancy Unrelated to Therapy | 0 | 0 | 0 | 1 | 0 |
| Cycle 1 (1 Month) | Protocol Violation | 1 | 0 | 1 | 0 | 0 |
| Cycle 2 (1 Month) | Discontinued Before Start of Cycle 3 | 10 | 1 | 3 | 3 | 6 |
| Cycle 2 (1 Month) | Lack of Efficacy | 1 | 3 | 7 | 6 | 16 |
| Cycle 2 (1 Month) | Lost to Follow-up | 0 | 0 | 2 | 2 | 1 |
| Cycle 2 (1 Month) | Non Resolving Cyst > 25mm | 1 | 0 | 0 | 0 | 0 |
| Cycle 2 (1 Month) | Other | 2 | 1 | 2 | 8 | 7 |
| Cycle 2 (1 Month) | Pregnancy Unrelated to Therapy | 0 | 1 | 0 | 0 | 0 |
| Cycle 3 (1 Month) | Lost to Follow-up | 0 | 2 | 0 | 0 | 1 |
| Cycle 3 (1 Month) | Other | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Clomiphene Citrate 50 mg | Anastrozole 1 mg | Anastrozole 5 mg | Anastrozole 10 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.0 years STANDARD_DEVIATION 3.9 | 28.8 years STANDARD_DEVIATION 3.9 | 29.6 years STANDARD_DEVIATION 3.9 | 29.3 years STANDARD_DEVIATION 3.4 | 29.2 years STANDARD_DEVIATION 3.8 |
| Sex: Female, Male Female | 77 Participants | 79 Participants | 76 Participants | 39 Participants | 271 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 | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 77 | 12 / 79 | 17 / 76 | 4 / 39 | 6 / 43 | 2 / 10 | 2 / 42 | 4 / 52 | 7 / 41 | 4 / 23 | 2 / 10 | 1 / 26 | 2 / 24 | 2 / 22 |
| serious Total, serious adverse events | 1 / 77 | 0 / 79 | 0 / 76 | 0 / 39 | 0 / 43 | 0 / 10 | 0 / 42 | 0 / 52 | 0 / 41 | 0 / 23 | 0 / 10 | 0 / 26 | 0 / 24 | 0 / 22 |
Outcome results
Primary
Ovulation Rate in Cycle 1
Ovulation rate was defined as the percentage of subjects who ovulated (mid-luteal Progesteron \[P4\] level greater than or equal to \[\>=\] 10 nanogram per milliliter \[ng/mL\] and/or pregnancy).
Time frame: Up to 1 month
Population: All Treated population included all treated subjects who received at least one tablet of study drug (clomiphene citrate or anastrozole).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clomiphene Citrate 50 mg | Ovulation Rate in Cycle 1 | 64.9 percentage of subjects |
| Anastrozole 1 mg | Ovulation Rate in Cycle 1 | 30.4 percentage of subjects |
| Anastrozole 5 mg | Ovulation Rate in Cycle 1 | 36.8 percentage of subjects |
| Anastrozole 10 mg | Ovulation Rate in Cycle 1 | 35.9 percentage of subjects |
Secondary
Number of Subjects With Clinical Pregnancy in Cycle 1
Clinical pregnancy was defined as the existence of at least one ultrasonographically confirmed gestational sac in the uterus with fetal heart activity.
Time frame: Up to 1 month
Population: All Treated population included all treated subjects who received at least one tablet of study drug (CC or anastrozole).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clomiphene Citrate 50 mg | Number of Subjects With Clinical Pregnancy in Cycle 1 | 10 subjects |
| Anastrozole 1 mg | Number of Subjects With Clinical Pregnancy in Cycle 1 | 4 subjects |
| Anastrozole 5 mg | Number of Subjects With Clinical Pregnancy in Cycle 1 | 7 subjects |
| Anastrozole 10 mg | Number of Subjects With Clinical Pregnancy in Cycle 1 | 0 subjects |