Trial Outcomes & Findings for 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 (NCT NCT01497197)

NCT ID: NCT01497197

Last Updated: 2015-11-09

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

174 participants

Primary outcome timeframe

34-38 hours post r-hCG administration

Results posted on

2015-11-09

Participant Flow

Participant milestones

Participant milestones
Measure
Gonal-f®+Luveris
GONAL f® (Liquid Pen; 300 international units \[IU\] of per day) stimulation Day 1-5 then followed by Luveris® (vial/powder, 150 IU per day) from stimulation Day 1 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 centre's standard practice.
Gonal-f® Followed by Luveris
GONAL-f® (Liquid Pen; 300 IU per day) stimulation Day 1-5 then added Luveris® (vial/powder, 150 IU per day) 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 centre's standard practice.
Overall Study
STARTED
89
85
Overall Study
COMPLETED
72
70
Overall Study
NOT COMPLETED
17
15

Reasons for withdrawal

Reasons for withdrawal
Measure
Gonal-f®+Luveris
GONAL f® (Liquid Pen; 300 international units \[IU\] of per day) stimulation Day 1-5 then followed by Luveris® (vial/powder, 150 IU per day) from stimulation Day 1 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 centre's standard practice.
Gonal-f® Followed by Luveris
GONAL-f® (Liquid Pen; 300 IU per day) stimulation Day 1-5 then added Luveris® (vial/powder, 150 IU per day) 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 centre's standard practice.
Overall Study
Lost to Follow-up
1
0
Overall Study
Protocol Violation
0
2
Overall Study
Withdrawal by Subject
2
1
Overall Study
Excessive/lack of response to treatment
1
0
Overall Study
Risk of OHSS
1
0
Overall Study
No oocytes retrieved
3
2
Overall Study
No fertilisation
6
5
Overall Study
Intention to freeze all embryos
0
1
Overall Study
All embryos discarded
0
3
Overall Study
Other
3
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Gonal-f®+Luveris
n=89 Participants
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 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.
Gonal-f® Followed by Luveris
n=85 Participants
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 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.
Total
n=174 Participants
Total of all reporting groups
Age, Continuous
37.8 years
STANDARD_DEVIATION 1.6 • n=5 Participants
38 years
STANDARD_DEVIATION 1.7 • n=7 Participants
37.9 years
STANDARD_DEVIATION 1.65 • n=5 Participants
Sex: Female, Male
Female
89 Participants
n=5 Participants
85 Participants
n=7 Participants
174 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 34-38 hours post r-hCG administration

Population: Modified intention-to-treat (MITT) included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following recombinant human follicle stimulating hormone (r-hFSH) stimulation and r-hCG injection).

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.

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=86 Participants
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 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.
Gonal-f® Followed by Luveris
n=82 Participants
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 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.
Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation
8.6 oocytes
Standard Deviation 6.54
8.7 oocytes
Standard Deviation 5.77

SECONDARY outcome

Timeframe: Screening

Population: Data was not analysed as per planned analysis due to frequent protocol violations/deviations, there was no subject eligible to be analyzed per protocol.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 days post stimulation (Number of stimulation days+6 days)

Population: MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection).

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

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=86 Participants
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 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.
Gonal-f® Followed by Luveris
n=82 Participants
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 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.
Total Number of Stimulation Treatment Days
11.1 days
Standard Deviation 2.42
11.3 days
Standard Deviation 2.24

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration

Population: MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all subjects who showed positive pregnancy test and evaluable for this outcome measure.

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

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=19 Participants
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 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.
Gonal-f® Followed by Luveris
n=21 Participants
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 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.
Implantation Rate
0.5 fetal sacs/embryo transferred
Standard Deviation 0.51
0.4 fetal sacs/embryo transferred
Standard Deviation 0.51

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration

Population: MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all participants who showed positive pregnancy test and evaluable for this outcome measure.

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

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=19 Participants
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 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.
Gonal-f® Followed by Luveris
n=21 Participants
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 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.
Number of Fetal Sacs With Activity
0.8 Fetal sacs
Standard Deviation 0.42
1.1 Fetal sacs
Standard Deviation 0.54

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration

Population: MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all participants who showed positive pregnancy test and evaluable for this outcome measure.

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

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=19 Participants
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 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.
Gonal-f® Followed by Luveris
n=21 Participants
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 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.
Number of Fetal Sacs With Detectable Heart Beats
0.6 Fetal sacs
Standard Deviation 0.50
1.0 Fetal sacs
Standard Deviation 0.45

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration

Population: MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection).

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.

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=86 Participants
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 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.
Gonal-f® Followed by Luveris
n=82 Participants
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 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.
Total Pregnancy Rate and Clinical Pregnancy Rate
Total pregnancy
20 percentage of subjects
27 percentage of subjects
Total Pregnancy Rate and Clinical Pregnancy Rate
Clinical pregnancy
17 percentage of subjects
23 percentage of subjects

SECONDARY outcome

Timeframe: Up to 85 days

Population: MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection).

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

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=86 Participants
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 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.
Gonal-f® Followed by Luveris
n=82 Participants
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 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.
Cycle Cancellation Rate Prior to r-hCG
0 percentage of subjects
0 percentage of subjects

SECONDARY outcome

Timeframe: 35 to 42 days post r-hCG administration

Population: MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection).

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.

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=86 Participants
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 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.
Gonal-f® Followed by Luveris
n=82 Participants
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 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.
Number of Subjects With Biochemical Pregnancies
2 subjects
1 subjects

SECONDARY outcome

Timeframe: 35 to 42 days post r-hCG administration

Population: MITT included all subjects randomized into trial who received at least 1 dose of Gonal-f® or Luveris®, and completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). 'N'=signifies all subjects who showed positive pregnancy test and evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=19 Participants
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 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.
Gonal-f® Followed by Luveris
n=21 Participants
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 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.
Number of Subjects With Multiple Pregnancies
0 subjects
4 subjects

SECONDARY outcome

Timeframe: Baseline up to 15-20 days post r-hCG administration

Population: Safety population included all randomized subjects who received at least one dose of the trial treatment.

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.

Outcome measures

Outcome measures
Measure
Gonal-f®+Luveris
n=89 Participants
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 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.
Gonal-f® Followed by Luveris
n=85 Participants
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 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.
Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs
27 subjects
28 subjects
Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
Serious AEs
4 subjects
5 subjects
Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Death
0 subjects
0 subjects
Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Discontinuation
1 subjects
3 subjects

Adverse Events

Gonal-f®+Luveris

Serious events: 4 serious events
Other events: 24 other events
Deaths: 0 deaths

Gonal-f® Followed by Luveris

Serious events: 5 serious events
Other events: 27 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Gonal-f®+Luveris
n=89 participants at risk
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 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.
Gonal-f® Followed by Luveris
n=85 participants at risk
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 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.
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
2.2%
2/89 • Baseline up to 15-20 days post r-hCG administration
4.7%
4/85 • Baseline up to 15-20 days post r-hCG administration
Reproductive system and breast disorders
Ovarian cyst
2.2%
2/89 • Baseline up to 15-20 days post r-hCG administration
1.2%
1/85 • Baseline up to 15-20 days post r-hCG administration

Other adverse events

Other adverse events
Measure
Gonal-f®+Luveris
n=89 participants at risk
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 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.
Gonal-f® Followed by Luveris
n=85 participants at risk
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 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.
Injury, poisoning and procedural complications
Overdose
14.6%
13/89 • Baseline up to 15-20 days post r-hCG administration
16.5%
14/85 • Baseline up to 15-20 days post r-hCG administration
Investigations
Oestradiol increased
9.0%
8/89 • Baseline up to 15-20 days post r-hCG administration
9.4%
8/85 • Baseline up to 15-20 days post r-hCG administration
Investigations
Progesterone increased
0.00%
0/89 • Baseline up to 15-20 days post r-hCG administration
1.2%
1/85 • Baseline up to 15-20 days post r-hCG administration
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/89 • Baseline up to 15-20 days post r-hCG administration
1.2%
1/85 • Baseline up to 15-20 days post r-hCG administration
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
2.2%
2/89 • Baseline up to 15-20 days post r-hCG administration
5.9%
5/85 • Baseline up to 15-20 days post r-hCG administration
Reproductive system and breast disorders
Breast pain
1.1%
1/89 • Baseline up to 15-20 days post r-hCG administration
0.00%
0/85 • Baseline up to 15-20 days post r-hCG administration

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60