Female Infertility
Conditions
Brief summary
The purpose of this randomized, two-arm and open label study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose Crinone 8% intravaginal progesterone gel 90 mg for the luteal support in women who are unable to conceive a child and are 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 during treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn (s).
Detailed description
This article has been accepted for publication in Human Reproduction published by Oxford University Press.
Interventions
Oral Dydrogesterone 10 mg tablets tid
DRUGintravaginal progesterone gel 90 mg
Sponsors
PRA Health Sciences
Datamap
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 screening 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 at screening * 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 or at 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 prior 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) * Subject is not pregnant , confirmed by negative pregnancy or by Investigator Judgement * 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, HEENT (head, ears, eyes, nose, throat), 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 àny experimental drug or any 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 Acute urogenital disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound | 12 weeks´ gestation | Pregnancy rate defined as the presence of fetal heart beats at 12 weeks' gestation determined by transvaginal ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer) | Day 14 after embryo transfer | Positive biochemical pregnancy test on Day 14 after embryo transfer |
| Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth) | After delivery (about 9 months after IVF) | Live birth rate (percentage of participants with a live birth) |
| Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | After delivery (about 9 months after IVF) | The gender (number of delivered newborns that are male or female) |
Countries
Australia, Belgium, China, Germany, Hong Kong, India, Russia, Singapore, Thailand, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dydrogesterone Tablets 3x10 mg Dydrogesterone tablets 3x10 mg
Dydrogesterone 30 mg: Oral Dydrogesterone 10 mg tablets tid | 494 |
| Crinone 8% Intravaginal Progesterone Gel 90 mg Crinone 8% intravaginal progesterone gel 90 mg
intravaginal progesterone gel 90 mg OD | 489 |
| Total | 983 |
Baseline characteristics
| Characteristic | Crinone 8% Intravaginal Progesterone Gel 90 mg | Total | Dydrogesterone Tablets 3x10 mg |
|---|---|---|---|
| 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 | 489 Participants | 983 Participants | 494 Participants |
| Age, Continuous | 31.6 years STANDARD_DEVIATION 4.6 | 31.7 years STANDARD_DEVIATION 4.5 | 31.8 years STANDARD_DEVIATION 4.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 237 Participants | 487 Participants | 250 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 247 Participants | 484 Participants | 237 Participants |
| Region of Enrollment Australia | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Belgium | 85 participants | 165 participants | 80 participants |
| Region of Enrollment China | 108 participants | 122 participants | 114 participants |
| Region of Enrollment Germany | 79 participants | 157 participants | 78 participants |
| Region of Enrollment Hong Kong | 7 participants | 16 participants | 9 participants |
| Region of Enrollment India | 100 participants | 203 participants | 103 participants |
| Region of Enrollment Russia | 41 participants | 80 participants | 39 participants |
| Region of Enrollment Singapore | 9 participants | 19 participants | 10 participants |
| Region of Enrollment Thailand | 12 participants | 25 participants | 13 participants |
| Region of Enrollment Ukraine | 46 participants | 91 participants | 45 participants |
| Sex: Female, Male Female | 489 Participants | 983 Participants | 494 Participants |
| Sex: Female, Male Male | 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 518 | 0 / 512 | 4 / 221 | 0 / 201 |
| other Total, other adverse events | 50 / 518 | 35 / 512 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 71 / 518 | 67 / 512 | 28 / 221 | 23 / 201 |
Outcome results
Primary
Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound
Pregnancy rate defined as the presence of fetal heart beats at 12 weeks' gestation determined by transvaginal ultrasound.
Time frame: 12 weeks´ gestation
Population: Full Analysis Sample (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dydrogesterone Tablets 3x10 mg | Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound | 38.7 percentage of participants |
| Crinone 8% Intravaginal Progesterone Gel 90 mg | Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound | 35.0 percentage of participants |
Secondary
Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female)
The gender (number of delivered newborns that are male or female)
Time frame: After delivery (about 9 months after IVF)
Population: Full Analysis Sample (FAS). These are the number of delivered babies from the mothers in the FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dydrogesterone Tablets 3x10 mg | Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | Gender male | 105 number of newborns |
| Dydrogesterone Tablets 3x10 mg | Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | Gender female | 100 number of newborns |
| Crinone 8% Intravaginal Progesterone Gel 90 mg | Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | Gender male | 95 number of newborns |
| Crinone 8% Intravaginal Progesterone Gel 90 mg | Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female) | Gender female | 93 number of newborns |
Secondary
Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer)
Positive biochemical pregnancy test on Day 14 after embryo transfer
Time frame: Day 14 after embryo transfer
Population: Full Analysis Sample (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dydrogesterone Tablets 3x10 mg | Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer) | 47.4 percentage of participants |
| Crinone 8% Intravaginal Progesterone Gel 90 mg | Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer) | 43.8 percentage of participants |
Secondary
Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth)
Live birth rate (percentage of participants with a live birth)
Time frame: After delivery (about 9 months after IVF)
Population: Full Analysis Sample (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dydrogesterone Tablets 3x10 mg | Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth) | 34.4 percentage of participants |
| Crinone 8% Intravaginal Progesterone Gel 90 mg | Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth) | 32.5 percentage of participants |