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Trial · Interventional

TerminatedPhase 3Results postedRegistry data

A Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® and Luveris® Starting on Day 1 Versus Day 6 in Women Undergoing Assisted Reproductive Technique

Overview

Status
Terminated
Phase
Phase 3
Enrollment
174 participants (actual)
Sponsor
Merck KGaA, Darmstadt, Germany · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United Arab Emirates

Start
May 2012
Primary completion
Jan 2014
Completion
Jan 2014
First posted
22 Dec 2011 (estimated)
Last update posted
9 Nov 2015 (estimated)
Conditions
Infertility · Fertility · Follicle Stimulating Hormone Deficiency

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2012201320142015
  1. Ph 3

    A Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® and Luveris® Starting on Day 1 Versus Day 6 in Women Undergoing Assisted Reproductive Technique

    NCT01497197

    May 2012 to Jan 2014

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a phase IIIb, interventional, multicenter, multinational, randomised, open-label, comparative trial which primary objective is to generate data on the ovarian stimulation profile obtained when Luveris® is started either on Day 1 or Day 6 in women in advanced reproductive age (36-42) undergoing Assisted Reproductive Technique (ART).

Interventions

  • GONAL-f®Drug
  • Luveris®Drug
  • Recombinant human chorionic gonadotropin (r-hCG)Biological

Arms2

  • Experimental

    Gonal-f®+Luveris®

    GONAL f® 300 international units \[IU\] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.

  • Experimental

    Gonal-f® Followed by Luveris®

    GONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation

    Time frame · 34-38 hours post r-hCG administration

    Registry description

    Ovarian stimulation was performed using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The total number of oocytes collected per subject following stimulation was reported.

Secondary outcomes(10)
  1. Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)

    Time frame · Screening

    Registry description

    Mean daily dose of FSH was to be determined by dividing the total daily dose by the number of stimulation days.

  2. Total Number of Stimulation Treatment Days

    Time frame · 6 days post stimulation (Number of stimulation days+6 days)

    Registry description

    The total number of stimulation treatment days for each subject was determined based on the treatment administration information collected in the case report form.

  3. Implantation Rate

    Time frame · 35-42 days post r-hCG administration

    Registry description

    The implantation rate was determined as number of fetal sacs divided by the number of embryos transferred post r-hCG administration.

  4. Number of Fetal Sacs With Activity

    Time frame · 35-42 days post r-hCG administration

    Registry description

    Number of fetal sacs with activity was evaluated by ultrasound scan (US) on Days 35-42 post r-hCG to confirm clinical pregnancy.

  5. Number of Fetal Sacs With Detectable Heart Beats

    Time frame · 35-42 days post r-hCG administration

    Registry description

    Number of fetal sacs with detectable heart beats was evaluated by US on Days 35-42 post r-hCG to confirm clinical pregnancy

  6. Total Pregnancy Rate and Clinical Pregnancy Rate

    Time frame · 35-42 days post r-hCG administration

    Registry description

    The subject was considered to have a positive pregnancy result if beta-hCG \>10 international units per liter (IU/L) and the subject had not menstruated between post-r-hCG Days 15-20. Clinical pregnancy was defined as the existence of at least an US confirmed gestational sac in the uterus with fetal heart activity post-r-hCG Days 35-42.

  7. Cycle Cancellation Rate Prior to r-hCG

    Time frame · Up to 85 days

    Registry description

    If the subject was not administered with r-hCG and withdrew prematurely from the trial, it was considered as cycle cancellation.

  8. Number of Subjects With Biochemical Pregnancies

    Time frame · 35 to 42 days post r-hCG administration

    Registry description

    Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Subjects with beta-hCG concentration greater than 10 IU/L were considered as biochemical pregnant.

  9. Number of Subjects With Multiple Pregnancies

    Time frame · 35 to 42 days post r-hCG administration

    Registry description

    Multiple pregnancy was defined as the existence of more than one ultrasound confirmed gestational sac in the uterus with fetal heart activity at post-r-hCG Days 35-42.

  10. Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation

    Time frame · Baseline up to 15-20 days post r-hCG administration

    Registry description

    An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious AE is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 34-38 hours post r-hCG administration

Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation

GroupValue (oocytes)Spread
Gonal-f®+Luveris8.66.54
Gonal-f® Followed by Luveris8.75.77
Secondary and other outcome results(7)
Secondary outcome· Screening

Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)

GroupValue
Gonal-f®+Luverisnot posted
Gonal-f® Followed by Luverisnot posted
Secondary outcomeMean· 6 days post stimulation (Number of stimulation days+6 days)

Total Number of Stimulation Treatment Days

GroupValue (days)Spread
Gonal-f®+Luveris11.12.42
Gonal-f® Followed by Luveris11.32.24
Secondary outcomeMean· 35-42 days post r-hCG administration

Implantation Rate

GroupValue (fetal sacs/embryo transferred)Spread
Gonal-f®+Luveris0.50.51
Gonal-f® Followed by Luveris0.40.51
Secondary outcomeMean· 35-42 days post r-hCG administration

Number of Fetal Sacs With Activity

GroupValue (Fetal sacs)Spread
Gonal-f®+Luveris0.80.42
Gonal-f® Followed by Luveris1.10.54
Secondary outcomeMean· 35-42 days post r-hCG administration

Number of Fetal Sacs With Detectable Heart Beats

GroupValue (Fetal sacs)Spread
Gonal-f®+Luveris0.60.50
Gonal-f® Followed by Luveris1.00.45
Secondary outcomeNumber· 35-42 days post r-hCG administration

Total Pregnancy Rate and Clinical Pregnancy Rate

GroupValue (percentage of subjects)
Gonal-f®+Luveris20
Gonal-f® Followed by Luveris27
Secondary outcomeNumber· Up to 85 days

Cycle Cancellation Rate Prior to r-hCG

GroupValue (percentage of subjects)
Gonal-f®+Luveris0
Gonal-f® Followed by Luveris0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Gonal-f®+LuverisGONAL f® 300 international units \[IU\] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.–4 / 8924 / 89
Gonal-f® Followed by LuverisGONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.–5 / 8527 / 85

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 36 Years up to 42 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Should be a female subject justifying an In Vitro Fertilization/Embryo transfer (IVF)/ET treatment * Should be between 36th and 42nd birthday (both included) at the time of the randomization visit * Have early follicular phase (day 2-4) serum level of basal FSH \<= 12 IU/L measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down regulation start) * Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length * Presence of both ovaries * Normal uterine cavity, which in the investigator's opinion is compatible with Pregnancy * Have a negative cervical Papanicolaou (PAP or smear) test within the last 6 months prior to randomization * Have at least one wash-out cycle (defined as \>=30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting GnRH agonist therapy * Be willing and able to comply with the protocol for the duration of the trial * Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care * Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intra-cytoplasmic sperm injection (ICSI) according to the center's standard practice Exclusion Criteria: * Had 2 (or more) previous ART cycles with a poor response to gonadotrophin stimulation defined as 6 (or less) mature follicles and/or 4 (or less) oocytes collected in any previous IVF cycle or previous cycles with a hyper response defined as 25 (or more) oocytes retrieved * Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible * Had previous severe ovarian hyperstimulation syndrome (OHSS) * Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS * Presence of endometriosis requiring treatment * Uterine myoma requiring treatment * Any contraindication to being pregnant and/or carrying a pregnancy to term * Extra-uterine pregnancy within the last 3 months prior to screening * History of 3 or more miscarriages (early or late miscarriages) due to any cause * Tumours of the hypothalamus and pituitary gland * Ovarian enlargement or cyst of unknown etiology * Ovarian, uterine or mammary cancer * A clinically significant systemic disease * Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner * Abnormal gynecological bleeding of undetermined origin * Known allergy or hypersensitivity to human gonadotrophin preparations * Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years prior to the screening visit * Entered previously into this trial or simultaneous participation in another clinical trial * Pregnancy and lactation period * Participation in another clinical trial within the past 30 days

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