Female Infertility
Conditions
Brief summary
Female inability to conceive a child. The purpose of this randomized, two-arm and double blind, double dummy study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose of 3x200 mg micronized progesterone capsules administered intravaginally for the luteal support in patients undergoing IVF. The treatment will start on the day of oocyte retrieval and continue until pregnancy is negative or until week 12 gestation.Patients will be followed after treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn(s).
Interventions
Oral Dydrogesterone 10 mg tablets tid
Intravaginal micronized progesterone 200 mg capsules tid
Placebo intravaginal micronized progesterone 200 mg capsules tid
DRUGPlacebo dydrogesterone
placebo oral dydrogesterone 10 mg tablets tid
Sponsors
Quintiles, Inc.
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
19 Years to 41 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Premenopausal females, age \> 18 years \< 42 years * Non-smokers. For females who were past smokers, they must have stopped tobacco usage for at least 3 months prior baseline visit * Early follicular phase (Day 2-4) Follicle stimulating hormone (FSH) less than or equal to 15 IU/L and estradiol (E2)within normal limits * Luteinizing hormone (LH), prolactin (PRL), T (testosterone) and thyroid-stimulating hormone (TSH), within the normal limits for the clinical laboratory, or considered not clinically significant by the Investigator within 6 months prior to screening * Documented history of infertility (e.g., unable to conceive for at least one year or for 6 months for women ≥ 38 years of age or bilateral tubal occlusion or absence) * Normal transvaginal ultrasound at screening (or within 14 days of screening) without evidence of clinically significant abnormality consistent with finding adequate for Assisted Reproductive Technology (ART) with respect to uterus and adnexa (no hydrosalpinx or clinically relevant uterine fibroids) * Negative pregnancy test on the day of pituitary down regulation (prior to administration of gonadotropin releasing hormones (GnRH) agonist or GnRH antagonist) * Clinically indicated protocol for induction of IVF with a fresh embryo * Single or dual embryo transfer * BMI ≥ 18 and ≤ 30 kg/m2
Exclusion criteria
* Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, head, ears, eyes, nose, throat (HEENT), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (\< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study * Acute urogenital disease * Known allergic reactions to progesterone products * Known allergic reactions to peanuts and peanut oil * Intake of experimental drug or participation in any other clinical trial within 30 days prior to study start * Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects to participate in or to complete the study * Current or recent substance abuse, including alcohol and tobacco (Note: Patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed) * History of chemotherapy or radiotherapy * Patients with more than 3 unsuccessful IVF attempts * Contraindication for pregnancy * Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests * History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound | 12 weeks´ gestation (at visit 6) | Percentage of participants being pregnant as measured by the presence of fetal heart beats at 12 weeks´gestation using transvaginal ultrasound |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer | Day 14 after embryo transfer | Percentage of participants being pregnant as measured by the positive biochemical pregnancy test on Day 14 after embryo transfer |
| Percentage of Participants With a Successful Completion of Pregnancy | After delivery (about 9 months after IVF) | Incidence of live births and healthy newborns |
| Gender of the Newborn | After delivery (about 9 months after IVF) | was recorded and collected for Newborn |
Countries
Austria, Belgium, Finland, Germany, Israel, Russia, Spain
Participant flow
Pre-assignment details
1070 subjects were enrolled in the study and 1031 subjects were randomized
Participants by arm
| Arm | Count |
|---|---|
| Dydrogesterone 30 mg Dydrogesterone 30 mg: Oral Dydrogesterone 10 mg tablets tid
Placebo progesterone: Placebo intravaginal micronized progesterone 200 mg capsules tid | 497 |
| Micronized Progesterone 600 mg Micronized Progesterone 600 mg: Intravaginal micronized progesterone 200 mg capsules tid
Placebo dydrogesterone: placebo oral dydrogesterone 10 mg tablets tid | 477 |
| Total | 974 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 64 | 82 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | pregnancy not confirmed at visit 4 | 248 | 249 |
| Overall Study | Protocol Violation | 24 | 28 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Dydrogesterone 30 mg | Micronized Progesterone 600 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 497 Participants | 477 Participants | 974 Participants |
| Age, Continuous | 32.5 years STANDARD_DEVIATION 4.5 | 32.5 years STANDARD_DEVIATION 4.4 | 32.5 years STANDARD_DEVIATION 4.4 |
| Region of Enrollment Austria | 7 participants | 7 participants | 14 participants |
| Region of Enrollment Belgium | 194 participants | 182 participants | 376 participants |
| Region of Enrollment Finland | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Germany | 62 participants | 60 participants | 122 participants |
| Region of Enrollment Israel | 69 participants | 66 participants | 135 participants |
| Region of Enrollment Russian Federation | 106 participants | 103 participants | 209 participants |
| Region of Enrollment Spain | 55 participants | 54 participants | 109 participants |
| Sex: Female, Male Female | 497 Participants | 477 Participants | 974 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 156 / 518 | 147 / 511 |
| serious Total, serious adverse events | 56 / 518 | 68 / 511 |
Outcome results
Primary
Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound
Percentage of participants being pregnant as measured by the presence of fetal heart beats at 12 weeks´gestation using transvaginal ultrasound
Time frame: 12 weeks´ gestation (at visit 6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dydrogesterone 30 mg | Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound | 37.6 percentage of participants |
| Micronized Progesterone 600 mg | Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound | 33.1 percentage of participants |
Secondary
Gender of the Newborn
was recorded and collected for Newborn
Time frame: After delivery (about 9 months after IVF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dydrogesterone 30 mg | Gender of the Newborn | Gender male | 120 number of newborns |
| Dydrogesterone 30 mg | Gender of the Newborn | Gender female | 93 number of newborns |
| Micronized Progesterone 600 mg | Gender of the Newborn | Gender male | 88 number of newborns |
| Micronized Progesterone 600 mg | Gender of the Newborn | Gender female | 70 number of newborns |
Secondary
Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer
Percentage of participants being pregnant as measured by the positive biochemical pregnancy test on Day 14 after embryo transfer
Time frame: Day 14 after embryo transfer
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dydrogesterone 30 mg | Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer | 47.1 percentage of participants |
| Micronized Progesterone 600 mg | Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer | 45.5 percentage of participants |
Secondary
Percentage of Participants With a Successful Completion of Pregnancy
Incidence of live births and healthy newborns
Time frame: After delivery (about 9 months after IVF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dydrogesterone 30 mg | Percentage of Participants With a Successful Completion of Pregnancy | Live birth rate | 34.6 percentage of participants |
| Dydrogesterone 30 mg | Percentage of Participants With a Successful Completion of Pregnancy | Healthy newborn rate | 32 percentage of participants |
| Micronized Progesterone 600 mg | Percentage of Participants With a Successful Completion of Pregnancy | Live birth rate | 29.8 percentage of participants |
| Micronized Progesterone 600 mg | Percentage of Participants With a Successful Completion of Pregnancy | Healthy newborn rate | 27.7 percentage of participants |