Clinical trial NCT03677336: Oral Dydrogesterone (OD) Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in IVF/ICSI
Official title: Oral Dydrogesterone Versus Micronized Vaginal Progesterone for Luteal Phase Support in In Vitro Fertilisation (IVF)/ IntraCytoplasmic Sperm Injection (ICSI): Pharmacokinetics and the Impact on the Endometrium, the Microbiota of the Genital Tract and the Peripheral Immunology. Double Blind Crossover Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility, Female
Infertility
Genital Diseases, Male
Genital Diseases, Female
Progesterone
Dydrogesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Progestins
Lead sponsor: CRG UZ Brussel
Sponsor class: OTHER
Collaborators: name: Universitätsklinikum Hamburg-Eppendorf
name: Abbott
name: KU Leuven
First posted: 2018-09-19
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomised, cross-over, double blind double dummy study
Primary purpose: TREATMENT

Brief summary: Female inability to conceive a child. The purpose of this prospective randomized, double-blinded, double dummy, two-arm cross-over study is to investigate the difference on histological, transcriptional and immunological level in endometrium between 3x10mg Dydrogesterone oral tablets and 3x200 mg Micronized progesterone intravaginal capsules for the luteal support in egg cell donors. Beside that, the pharmacokinetics, the impact on the peripheral immunology (by blood sampling) and the microbiota (by genital swabs) will be investigated.


Eligibility criteria: Inclusion Criteria:

* Oocyte donor candidates
* Regularly cycling
* BMI ≥18 and ≤ 29 kg/m2
* Signed informed consent
* Non-smokers.
* AMH \<7,53 and \>1,18 ng/mL (90th and 10th percentile for healthy women aged 25-29 according to the used Elecsys® AMH kit by Roche)
* PRL, T and TSH within the normal limits for the clinical laboratory, or considered not clinically significant by the investigator within 6 months prior or at screening

Exclusion Criteria:

* Intra-uterine device
* Previous enrollment
* 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 during the course of the study
* Known allergic reactions to progesterone / dydrogesterone products (active substance or to any of the excipients)
* Intake of any 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 in or to complete the study.
* Current or recent substance abuse, including alcohol and tobacco (patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
* Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests.
* Known or suspected progestogen dependent neoplasms (e.g. meningioma)
* Serum progesterone level \>1.5 ng/mL at ovulation triggering

Primary outcomes:
measure: Molecular endometrial level using illumina RNA-seq
timeFrame: On the eight day (at 8am) of LPS intake
measure: Molecular endometrial level using immunohistochemistry
timeFrame: On the eight day (at 8am) of LPS intake
measure: Molecular endometrial level using flow cytometry
timeFrame: On the eight day (at 8am) of LPS intake
Secondary outcomes:
measure: Difference in pharmacokinetic profile: Progesterone: AUC0-τ
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: AUC0-t
timeFrame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.
measure: Difference in pharmacokinetic profile: Progesterone: Cmax
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: tmax
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: Ctrough
timeFrame: On the eight day of LPS intake: 1 hour before morning dose.
measure: Difference in pharmacokinetic profile: Progesterone: λz
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: t1/2
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: CL/F
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Progesterone: Vz/F
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: AUC0-τ
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of AUC0-τ of dydrogesterone and DHD
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: AUC0-t
timeFrame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of AUC0-t of dydrogesterone and DHD
timeFrame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Cmax
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of Cmax of dydrogesterone and DHD
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: tmax
timeFrame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Ctrough
timeFrame: On the eight day of LPS intake: 1 hour before morning dose.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: λz
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: t1/2
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: CL/F
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Vz/F
timeFrame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.
measure: Difference in peripheral immunology
timeFrame: On the first and eight day of LPS intake, 1hour before morning dose at 9 am.
measure: Difference in microbiota in the female genital tract
timeFrame: On the first and eight day of LPS intake, 1 hour before morning dose at 9 am.
Other outcomes:
Locations:
city: Jette
country: Belgium
facility: Centrum voor Reproductieve Geneeskunde
state: Brussel
Study officials:
affiliation: Head of department CRG
name: Herman Tournaye, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tournaye H, Sukhikh GT, Kahler E, Griesinger G. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017 May 1;32(5):1019-1027. doi: 10.1093/humrep/dex023.