Hypogonadism
Conditions
Keywords
Hypogonadism, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant leutinizing hormone (r-hLH)
Brief summary
This was a prospective, open, non-comparative study to evaluate the safety and efficacy of recombinant human luteinizing hormone (rhLH, Luveris) administered subcutaneously (s.c.) in follicular development during ovulation induction in 31 Chinese female subjects with hypogonadotropic hypogonadism.
Detailed description
The objective of this prospective, open, non-comparative study was to assess the safety and efficacy of rhLH (Luveris) administered subcutaneously in follicular development during ovulation induction in Chinese female subjects with hypogonadotropic hypogonadism. The study was organized on an outpatient basis involving a single cycle of treatment. Prior to entry into the study, the diagnosis of hypogonadotropic hypogonadism was confirmed by history, by the presence or absence of specific clinical features and by measuring serum gonadotropin levels. Once a subject has signed the informed consent form and after satisfying all eligibility criteria, the subject received a combination of daily injection of recombinant human follicle-stimulating hormone (rhFSH) 150 international units (IU) plus rhLH 75 IU. After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU human chorionic gonadotropin (hCG). Luteal phase function was assessed by serum progesterone level determination.
Interventions
One r-hLH (75 International Units \[IU\]) injection s.c. once daily.
DRUGRecombinant human follicle-stimulating hormone (r-hFSH)
One r-hFSH (150 IU) injection s.c. once daily.
After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU hCG.
Sponsors
Merck Pte. Ltd., Singapore
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Be premenopausal, between 18 and 39 years of age * Have a clinical history of hypogonadotropic hypogonadism, and laboratory test result comply with diagnosis of hypogonadotropic hypogonadism during screening procedure * Have discontinued gonadotropins, gonadotropin-releasing hormone (GnRH) (gonadotropin naïve), or estrogen progesterone replacement therapy at least one month before the screening procedure * Have a negative progestin challenge test performed during screening * Have the following hormonal values in a centrally analyzed fasting blood sample, drawn within 6 months before initiation of treatment: * Follicular stimulating hormone (FSH): \< 5 international units/liter (IU/L) * Luteinizing hormone (LH): \< 1.2 IU/L * Oestradiol (E2): \< 60 picogram/milliliter (pg/mL) (\<220 picomolar/liter \[pmol/L\]) * Prolactin (PRL): \< 44.3 nanogram/milliliter (ng/mL) (\< 1040 milli-international units/liter \[mIU/L\]) * Thyrotrophin-stimulating hormone (TSH): \< 6.5 micro-international units (uIU/mL) * Free Thyroxine (T4): 0.8-1.8 nanogram/deciliter (ng/dL) (11-24 pmol/L) * Triiodothyronine (T3): \< 1.0 ng/mL (\< 3.5 nanomolar/liter \[nmol/L\]) * Have an endovaginal pelvic ultrasound scan showing (i) no ovarian tumor and cyst \< 2 centimeters (cm); (ii) no clinically significant uterine abnormality, and (iii) \< 13 mm small follicles (mean diameter \< 10 mm) on the largest section through each ovary * Have a normal cervical pap smear within 6 months of the initial visit * Have a body mass index (BMI) between 18.4 and 31.4 kilogram/meter square (kg/m\^2) * Be willing and able to comply with the protocol for the duration of the study * Have given written informed consent prior to any study related procedure
Exclusion criteria
* Ongoing pregnancy * Any chronic systemic disease * Hypersensitive to study drug and control drug * History of severe ovarian hyperstimulation syndrome * Abnormal gynecological bleeding of undetermined origin * Previous or current hormone dependent tumor * Known active substance abuse or eating disorder * Known central nervous system (CNS) lesions: In cases where hypogonadotropic hypogonadism (HH) is secondary to a CNS lesion or its treatment, the subject will not be eligible without consulting Serono's Medical Director * Exercise program exceeding 10 hours per week * Currently undergoing treatment with psychotropic medication or with any other medication known to interfere with normal reproductive function (for example, neuroleptics, dopamine antagonists) * There is any abnormality, decided by investigators, which might produce effect on the absorption, distribution and excretion of investigational drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Met Both Index 1 and Index 2 | Day 14 | The three indices were defined as; Index 1: diameter of at least one follicle is greater than 17 mm; Index 2: serum oestradiol (E2) level in blood serum above 109 picogram/ milliliter (pg/mL) on human chorionic gonadotropin (hCG) injection day; Index 3: participant refuses to take hCG injection for the concern of ovarian hyperstimulation syndrome (OHSS) or participant is pregnant. A subset of these participants met Index 3. |
| Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter | Day 14 | — |
| Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection | Day 14 | — |
| Number of Participants Who Refused to Take hCG Injection | Day 14 | Participant refused to take hCG injection for the concern of OHSS or the participant was pregnant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle | Day 14 | — |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 14 | AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. |
| Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle | Day 14 | — |
| Average Change of E2 Level in Participants Per Day up to Day 14 | up to Day 14 | The average change was calculated by assessing the E2 levels on 4 timepoints until day 14 (day 1, day 5, day 10, day 14 \[hCG administration day\]). |
| Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies | Day 14 | Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) Recombinant human luteinizing hormone (rhLH, Luveris) injection 75 international units (IU) subcutaneously (s.c.) daily along with 150 IU recombinant human follicle-stimulating hormone (rhFSH, Gonal-F) s.c. daily for no longer than 14 days unless the diameter of ovarian follicles indicated the maturation (greater than 14 millimeter \[mm\]). | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Recombinant Human Luteinizing Hormone (Luveris) |
|---|---|
| Age, Continuous | 30.1 years STANDARD_DEVIATION 4.09 |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter | 23 participants |
Primary
Number of Participants Who Met Both Index 1 and Index 2
The three indices were defined as; Index 1: diameter of at least one follicle is greater than 17 mm; Index 2: serum oestradiol (E2) level in blood serum above 109 picogram/ milliliter (pg/mL) on human chorionic gonadotropin (hCG) injection day; Index 3: participant refuses to take hCG injection for the concern of ovarian hyperstimulation syndrome (OHSS) or participant is pregnant. A subset of these participants met Index 3.
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants Who Met Both Index 1 and Index 2 | 23 participants |
Primary
Number of Participants Who Refused to Take hCG Injection
Participant refused to take hCG injection for the concern of OHSS or the participant was pregnant.
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants Who Refused to Take hCG Injection | Refused due to concern of OHSS | 0 participants |
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants Who Refused to Take hCG Injection | Refused due to pregnancy | 10 participants |
Primary
Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection | 23 participants |
Secondary
Average Change of E2 Level in Participants Per Day up to Day 14
The average change was calculated by assessing the E2 levels on 4 timepoints until day 14 (day 1, day 5, day 10, day 14 \[hCG administration day\]).
Time frame: up to Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Average Change of E2 Level in Participants Per Day up to Day 14 | 71.03 pg/mL per day | Standard Deviation 64.53 |
Secondary
Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle | 3.57 follicles | Standard Deviation 4.07 |
Secondary
Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle | 2.13 follicles | Standard Deviation 2 |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.
Time frame: Day 14
Population: Safety analysis set included all participants who received investigational drug for at least one time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 0 participants |
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 0 participants |
Secondary
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies
Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.
Time frame: Day 14
Population: Per protocol set included all participants who completely met all the requirements of clinical trial protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies | Biochemical Pregnancies | 1 participants |
| Recombinant Human Luteinizing Hormone (Luveris) | Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies | Clinical Pregnancies | 9 participants |