Phase 3 Trial to Evaluate the Efficacy and Safety of COL-1620 Vaginal Progesterone Gel

Phase 3

Completed

Conditions: Luteal Hormone Supplementation in In-vitro Fertilization
Embryo Transfer

Interventions: Drug: COL-1620
Drug: Gonadotropin-releasing hormone (GnRH) analogue
Drug: Follicle-stimulating hormone (FSH)
Drug: Human Chorionic Gonadotropin (hCG)

Registration Number: NCT01863680

Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary: The primary objective of this trial is to demonstrate the non-inferiority of the clinical pregnancy rate per embryo transfer to the historical standard value in in-vitro fertilization (IVF)/embryo transfer (ET) cycles in Japan (Japan Society of Obstetrics and Gynecology \[JSOG\] 2009 registry data: 24.3 percent \[%\]). The secondary objectives of this trial are to assess the biochemical pregnancy rate per ET, pharmacokinetics, and safety of COL-1620.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 178

Inclusion Criteria

Japanese race
Woman with a history of infertility and in whom In-vitro fertilization and embryo transfer (IVF/ET) is indicated
The controlled ovarian stimulation (COS) therapy is gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) in combination with a follicle-stimulating hormone (FSH) containing preparation
Healthy premenopausal woman aged between 20 and 45 years (inclusive) and wishing to conceive
Body mass index (BMI) of 17.0 to 25.0 kilogram per square meter (kg/m^2) (inclusive)
A negative pregnancy test (urinary beta-human chorionic gonadotropin [hCG]) prior to starting COS
Normal cervical smear result (Papanicolaou [PAP] test: Negative for Intraepithelial Lesion or Malignancy [NILM] or [Atypical Squamous Cells of Undetermined Significance {ASC-US} and Human Papillomavirus {HPV} negative]) within 12 months prior to the date of informed consent. If not available, a cervical smear and HPV test will be performed as part of Screening
No clinically significant abnormal findings in the screening hematology, biochemistry and urinalysis parameters
Full comprehension of the study and voluntary written informed consent obtained in writing prior to any trial-related activities

Exclusion Criteria

History of recurrent pregnancy loss (defined as 3 or more previous spontaneous abortions)
History of 3 or more consecutive cancelled or failed (no clinical pregnancy) IVF/ET cycles
Abnormal hemorrhage of the reproductive tract of undetermined origin
Any contraindication to being pregnant and/or carrying a pregnancy to term (for example, malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy)
Uterine myoma requiring treatment
Extra-uterine pregnancy within the last 3 months prior to the date of informed consent
History or presence of intracranial tumor (for example, hypothalamic or pituitary tumor)
Presence of or suspected gonadotropin- or estrogen-dependent malignancy (for example, ovarian, uterine or mammary carcinoma)
Ovarian enlargement or cyst of unknown etiology
Breast-feeding or lactation
History of severe Ovarian Hyperstimulation Syndrome (OHSS) (Classification of OHSS Severity, as per Japan Reproductive/Endocrine Working Group)
Known Human Immunodeficiency Virus (HIV)-positive status, or a history of or current active infection with Hepatitis B or C
Known allergy or hypersensitivity to progesterone preparations or gonadotropin preparations and/or their excipients, or any contraindication to receive medication for controlled ovarian stimulation (for example, gonadotropin, GnRH analogues, combined oral contraceptive pill, as appropriate)
History of or suspected alcohol or substance abuse within 5 years prior to the date of informed consent
Clinically significant systemic disease (for example, insulin-dependent diabetes, epilepsy, severe migraine, acute porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)
Active thrombophlebitis, thromboembolic disorder or cerebral apoplexy, or a history of such conditions
Other significant disease that in the Investigator's or Sub-Investigator's opinion would exclude the subject from the trial
Participation in another clinical trial within 3 months prior to the date of informed consent or simultaneous participation in another clinical trial
Legal incapacity or limited legal capacity

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
COL-1620	COL-1620	-
COL-1620	Gonadotropin-releasing hormone (GnRH) analogue	-
COL-1620	Follicle-stimulating hormone (FSH)	-
COL-1620	Human Chorionic Gonadotropin (hCG)	-

Primary Outcome Measures

Name	Time	Method
Clinical Pregnancy Rate Per Embryo Transfer	Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])	Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred.

Secondary Outcome Measures

Name	Time	Method
Biochemical Pregnancy Rate Per Embryo Transfer	Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])	Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS during Visit 6 (Week 5), but with a positive serum beta-hCG pregnancy test result at Visit 5 (Day 14+/-3). Biochemical pregnancy rate was calculated as the number of subjects who had no fetal sac observed during Visit 6 (Week 5) TVUS assessment or subjects who had a positive serum pregnancy test at Visit 5 (Day 14+/-3) and no data recorded at Visit 6 (Week 5) divided by the number of subjects who has at least 1 embryo transferred.
Serum Progesterone Level	Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)	Two pharmacokinetic (PK) samples were collected per subject for the measurement of serum progesterone concentrations; 1st sample at Visit 2-2 (prior to hCG administration) and second sample during Visit 5 (Day 14+/-3, 7 hours after the morning of investigational medicinal product administration).