Trial Outcomes & Findings for A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve (NCT NCT01110707)
NCT ID: NCT01110707
Last Updated: 2018-03-27
Results Overview
Mean number of M-II oocytes were calculated for subjects undergoing ovum pick up for Intra-cytoplasmic Sperm Injection (ICSI). ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
131 participants
Primary outcome timeframe
36 hours post r-hCG administration
Results posted on
2018-03-27
Participant Flow
Participant milestones
| Measure |
r-hFSH + r-hLH
Subjects received subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]) along with subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Overall Study
STARTED
|
63
|
68
|
|
Overall Study
COMPLETED
|
63
|
65
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
r-hFSH + r-hLH
Subjects received subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]) along with subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
3
|
Baseline Characteristics
A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve
Baseline characteristics by cohort
| Measure |
r-hFSH + r-hLH
n=63 Participants
Subjects received subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]) along with subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
63 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
131 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: 36 hours post r-hCG administrationPopulation: The Intention-To-Treat (ITT) analysis set included all the randomized subjects who received at least 1 dose of study medication.
Mean number of M-II oocytes were calculated for subjects undergoing ovum pick up for Intra-cytoplasmic Sperm Injection (ICSI). ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Mean Number of Metaphase II (M-II) Oocytes Retrieved
|
6.7 M-II oocytes
Standard Deviation 4.1
|
7.0 M-II oocytes
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: 36 hours post r-hCG administrationPopulation: The ITT analysis set included all the randomized subjects who received at least 1 dose of study medication.
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Number of Fertilized Oocytes (2 Pronuclei [2PN])
|
3.1 2PN oocytes
Standard Deviation 2.3
|
3.3 2PN oocytes
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: Day 2-3 post r-hCG administrationPopulation: The ITT analysis set included all the randomized subjects who received at least 1 dose of study medication.
Embryos were classified into 5 different grades (1 to 5) based on their capacity of implantation. Grade 1 embryos were those with best capacity of implantation and Grade 5 embryos were those with worst capacity of implantation. Mean number of embryos for each of the 5 grades were reported.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Quality of Embryos
Grade 1
|
1.1 embryos
Standard Deviation 1.1
|
1.3 embryos
Standard Deviation 1.4
|
|
Quality of Embryos
Grade 2
|
1.1 embryos
Standard Deviation 1.5
|
1.2 embryos
Standard Deviation 1.1
|
|
Quality of Embryos
Grade 3
|
0.5 embryos
Standard Deviation 0.6
|
0.5 embryos
Standard Deviation 0.9
|
|
Quality of Embryos
Grade 4
|
0.3 embryos
Standard Deviation 0.5
|
0.2 embryos
Standard Deviation 0.6
|
|
Quality of Embryos
Grade 5
|
0.3 embryos
Standard Deviation 1.0
|
0.2 embryos
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: 35-42 days post r-hCG administrationPopulation: The ITT analysis set included all the randomized subjects who received at least 1 dose of study medication.
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Embryo Implantation Rate
|
18.1 Percent sacs per embryo
|
11.3 Percent sacs per embryo
|
SECONDARY outcome
Timeframe: 35-42 days post r-hCG administrationPopulation: The ITT analysis set included all the randomized subjects who received at least 1 dose of study medication.
Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Clinical Pregnancy Rate
|
27.0 Percentage of subjects
|
14.7 Percentage of subjects
|
SECONDARY outcome
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])Population: The ITT analysis included all the randomized subjects who received at least 1 dose of study medication.
Mean number of follicles as per the following categories were presented: \>=14 mm and less than (\<) 16 mm; \>=16 mm and \<18 mm and \>=18 mm.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
>=14 mm and <16 mm
|
2.2 Follicles
Standard Deviation 2.0
|
2.1 Follicles
Standard Deviation 1.9
|
|
Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
>=16 mm and <18 mm
|
2.3 Follicles
Standard Deviation 2.0
|
2.7 Follicles
Standard Deviation 2.1
|
|
Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
>=18 mm
|
4.0 Follicles
Standard Deviation 3.0
|
3.7 Follicles
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])Population: The ITT analysis set included all the randomized subjects who received at least 1 dose of study medication.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Endometrial Thickness
|
6.0 mm
Standard Deviation 3.2
|
5.9 mm
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])Population: The ITT analysis included all the randomized subjects who received at least one dose of study medication.
If the subject was not administered with r-hCG and withdrew prematurely from the trail, it is considered as cycle cancellation
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Number of Cycles Cancelled Due to Unsatisfactory Response
|
0 cycles
|
3 cycles
|
SECONDARY outcome
Timeframe: 36 hours post r-hCG administrationPopulation: The ITT analysis included all the randomized subjects who received at least 1 dose of study medication.
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocyte from the ovary of the female subject, enabling fertilization outside the body.
Outcome measures
| Measure |
r-hFSH + r-hLH
n=63 Participants
GONAL-f (follitropin alpha); a recombinant human follicular stimulating hormone (r-hFSH) injection 300-450 International Units (IU) subcutaneously (SC) was administered separately after achieving pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a) at a dose of 0.1 milligram per day (mg/day). Subjects also received Luveris; recombinant human luteinizing hormone (r-hLH) injection 150 IU/day SC until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 Participants
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Mean Number of Oocytes Retrieved
|
8.3 Oocytes
Standard Deviation 4.7
|
8.9 Oocytes
Standard Deviation 4.9
|
Adverse Events
r-hFSH + r-hLH
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
r-hFSH Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
r-hFSH + r-hLH
n=63 participants at risk
Subjects received subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]) along with subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation. Administration of both r-hFSH and r-hLH was suspended 36 hours before administering recombinant human chorionic gonadotrophin (r-hCG).
|
r-hFSH Alone
n=68 participants at risk
Subjects received subcutaneous injection of a recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day \[mg/day\]).
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Ovarian Hyperstimulation Syndrome
|
1.6%
1/63
|
0.00%
0/68
|
|
Pregnancy, puerperium and perinatal conditions
Pelvic Inflammatory Disease
|
1.6%
1/63
|
0.00%
0/68
|
Additional Information
Merck KGaA Communication Center
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER