A Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization (Lotus I)

A Double-Blind, Double-Dummy, Randomized, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization (Lotus I)

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).

Study Overview

• Status: Completed
• Conditions: Female Infertility
• Intervention / Treatment: Drug: Dydrogesterone 30 mg; Drug: Placebo progesterone; Drug: Micronized Progesterone 600 mg; Drug: Placebo dydrogesterone

• Study Type: Interventional
• Enrollment (Actual): 1070
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Site reference no. 113176
• Belgium
  • Brasschaat, Belgium, 2930
    • Site reference no. 93593
  • Brussels, Belgium, 1070
    • Site reference no. 93598
  • Brussels, Belgium, 1090
    • Site reference no. 93615
  • Brussels, Belgium, 1200
    • Site reference no. 93617
  • Genk, Belgium, 3600
    • Site reference no. 93613
  • Gent, Belgium, 9000
    • Site reference no. 93594
  • Gent, Belgium, 9000
    • Site reference no. 93597
  • Hasselt, Belgium, 3500
    • Site reference no. 93616
  • Leuven, Belgium, 3000
    • Site reference no. 93595
  • Mons, Belgium, 7000
    • Site reference no. 93614
• Finland
  • Helsinki, Finland, 00180
    • Site reference ID ORG-000884
  • Jyväskylä, Finland, 40100
    • Site reference ID ORG-000885
  • Oulu, Finland, 90014
    • Site reference no. ORG-000635
  • Tampere, Finland, 33100
    • Site reference ID ORG-000795
  • Turku, Finland, 20520
    • Site reference no. ORG-000633
• Germany
  • Berlin, Germany, 10117
    • Site reference ID ORG-000645
  • Berlin, Germany, 14050
    • Site reference ID ORG-000643
  • Dresden, Germany, 01307
    • Site reference ID ORG-000642
  • Heidelberg, Germany, 69120
    • Site reference ID ORG-000644
  • Luebeck, Germany, 23562
    • Site reference ID ORG-000883
• Israel
  • Be'er Sheva, Israel, 84101
    • Site reference no. 93635
  • Hadera, Israel, 38100
    • Research facility ID ORG-000934
  • Haifa, Israel, 3339419
    • Research facility ID ORG-000935
  • Jerusalem, Israel, 91120
    • Site reference no. 93638
  • Tel Aviv, Israel, 69710
    • Site reference no. 93641
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • FSBI "Ural SRI of Maternity and Child Protection" of MoH and SD
  • Ekaterinburg, Russian Federation, 620043
    • Center of Family Medicine LC
  • Moscow, Russian Federation, 117036
    • FGBU Endocrinology Research Center of Minzdrav of Russia
  • Moscow, Russian Federation, 117036
    • Moscow State Medical Dentistry University
  • Moscow, Russian Federation, 119192
    • CJSC "Nasledniki"
  • Moscow, Russian Federation, 127473
    • Moscow State Medical Dentistry University
  • St. Petersburg, Russian Federation, 191014
    • SBEIHPE - NWSMU n.a.l.l.Melnichko MoH and SD of RF
  • St. Petersburg, Russian Federation, 192174
    • St. Petersburg SBHI "Maternity Hospital No 17" (main address)
• Spain
  • Baracaldo, Vizcaya, Spain, 48903
    • Site reference no. 119915
  • Barcelona, Spain, 08017
    • Site reference ID ORG-000791
  • Bilbao, Spain, 48940
    • Site reference no. ORG-000639
  • Pozuelo de Alarcon (Madrid), Spain, 28223
    • Site reference no. ORG-000640
  • Sevilla, Spain, 41011
    • Site reference no. ORG-000638
  • Valencia, Spain, 46015
    • Site reference no. ORG-000637

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dydrogesterone 30 mg	Drug: Dydrogesterone 30 mg; Oral Dydrogesterone 10 mg tablets tid; Drug: Placebo progesterone; Placebo intravaginal micronized progesterone 200 mg capsules tid
Experimental: Micronized Progesterone 600 mg	Drug: Micronized Progesterone 600 mg; Intravaginal micronized progesterone 200 mg capsules tid; Drug: Placebo dydrogesterone; placebo oral dydrogesterone 10 mg tablets tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks´ gestation (at visit 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 14 after embryo transfer
Percentage of Participants With a Successful Completion of Pregnancy	Incidence of live births and healthy newborns	After delivery (about 9 months after IVF)
Gender of the Newborn	was recorded and collected for Newborn	After delivery (about 9 months after IVF)

Collaborators and Investigators

• Sponsor: Abbott
• Collaborators: Quintiles, Inc.
• Investigators: Study Director: Darline Cheatham-Seitz, MD, PhD, Abbott

Publications and helpful links

General Publications

• 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. Erratum In: Hum Reprod. 2017 Oct 1;32(10):2152.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: May 7, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Actual): January 2, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone; Dydrogesterone
• Other Study ID Numbers: M13-563; 2012-002215-26 (EudraCT Number)