Oral Dydrogesterone (OD) Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in IVF/ICSI

NCT03677336 | Completed Phase 4 DMC

• 2 other identifiers: DYDRA0012018-000105-23
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility, Female; Infertility; Genital Diseases, Male; Genital Diseases, Female; Progesterone; Dydrogesterone; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Progestins

Outcome Measures

Primary Outcomes (3)

• Molecular endometrial level using illumina RNA-seq

  To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using Illumina RNA-seq on endometrial derived single cell suspensions

  On the eight day (at 8am) of LPS intake

• Molecular endometrial level using immunohistochemistry

  To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using immunohistochemistry on endometrial derived single cell suspensions

  On the eight day (at 8am) of LPS intake

• Molecular endometrial level using flow cytometry

  To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using flow cytometry on endometrial derived single cell suspensions

  On the eight day (at 8am) of LPS intake

Secondary Outcomes (23)

• Difference in pharmacokinetic profile: Progesterone: AUC0-τ

  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.

• Difference in pharmacokinetic profile: Progesterone: AUC0-t

  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.

• Difference in pharmacokinetic profile: Progesterone: Cmax

  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.

• Difference in pharmacokinetic profile: Progesterone: tmax

  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.

• Difference in pharmacokinetic profile: Progesterone: Ctrough

  On the eight day of LPS intake: 1 hour before morning dose.

Study Arms (2)

Group l: 1st cycle MVP/placebo OD

OTHER

2 cycles of controlled ovarian stimulation, dual triggering, oocyte retrieval (OR) and LPS, with an interval period of 2 to 12 months. The only difference of the second cycle being the other LPS study medication as compared to the first cycle. * 1st cycle: Start on day of oocyte retrieval (OR) (=d1): Dydrogesterone Oral Tablet 10 mg 3 times daily + Placebo micronized vaginal progesterone 200 mg capsules 3 times daily, for 8 days. * 2nd cycle: Start on day of oocyte retrieval (OR) (=day 1): 'Micronized Progesterone 200 mg intravaginal capsules 3 times daily + placebo 'Dydrogesterone Oral Tablet 10 mg 3 times daily, for 8 days.

Drug: Dydrogesterone Oral Tablet; Drug: Micronized progesterone; Drug: Placebo Dydrogesterone oral tablet; Drug: Placebo Micronized progesterone

Group ll: 1st cycle placebo MVP/OD

OTHER

2 cycles of controlled ovarian stimulation, dual triggering, oocyte retrieval (OR) and LPS, with an interval period of 2 to 12 months. The only difference of the second cycle being the other LPS study medication as compared to the first cycle. * 1st cycle: Start on day of oocyte retrieval (OR) (=day 1): Micronized Progesterone 200 mg intravaginal capsules 3 times daily + placebo Dydrogesterone Oral Tablet 10 mg 3 times daily, for 8 days. * 2nd cycle: Start on day of oocyte retrieval (OR) (=day 1): Dydrogesterone Oral Tablet 10 mg 3 times daily + Placebo micronized progesterone 200 mg intravaginal capsules 3 times daily, for 8 days.

Drug: Dydrogesterone Oral Tablet; Drug: Micronized progesterone; Drug: Placebo Dydrogesterone oral tablet; Drug: Placebo Micronized progesterone

Interventions

Dydrogesterone Oral Tablet DRUG

Tablet, oral, 10 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Also known as: OD, Duphaston

Group l: 1st cycle MVP/placebo OD; Group ll: 1st cycle placebo MVP/OD

Micronized progesterone DRUG

Capsule, vaginal, 200 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Also known as: MVP, Utrogestan

Group l: 1st cycle MVP/placebo OD; Group ll: 1st cycle placebo MVP/OD

Placebo Dydrogesterone oral tablet DRUG

Tablet, indistinguishable from dydrogesterone oral tablet

Also known as: Placebo OD

Group l: 1st cycle MVP/placebo OD; Group ll: 1st cycle placebo MVP/OD

Placebo Micronized progesterone DRUG

Capsule, indistinguishable from micronized vaginal progesterone capsules

Also known as: Placebo MVP

Group l: 1st cycle MVP/placebo OD; Group ll: 1st cycle placebo MVP/OD

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CRG UZ Brussel: lead
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Abbott: collaborator
• KU Leuven: collaborator

Study Sites (1)

Centrum voor Reproductieve Geneeskunde

Jette, Brussels Capital, 1090, Belgium

Location

Related Publications (1)

• 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.

  PMID: 28333318 BACKGROUND

MeSH Terms

Conditions

Infertility, Female; Infertility; Genital Diseases, Male; Genital Diseases, Female

Interventions

Dydrogesterone; Progesterone; Utrogestan

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Herman Tournaye, PhD, MD

  Head of department CRG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded and packaged medication will be provided to the investigational site and dispensed to the participants. The participants, their treating physicians and the investigators will be blinded for the randomization of subjects to the treatment groups. Of both treatment medications, OD and MVP, a placebo version will be available and administered in both oocyte donation cycles. The medication will be given in a double blind double dummy fashion. All the tablets and capsules will be identical in appearance, shape, smell and taste, and packaged in the proper proportion to assure desired dosages and maintenance of the blinding.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: A randomised, cross-over, double blind double dummy study

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 19, 2018
• Study Start: May 1, 2019
• Primary Completion: August 24, 2020
• Study Completion: August 24, 2020
• Last Updated: December 17, 2020

Record last verified: 2020-12

Locations

BE (1)