A Study Using Recombinant Human Luteinizing Hormone (r-hLH, Luveris®) in the Treatment of Chinese Women With Hypogonadotropic Hypogonadism

Hypogonadism Clinical Trial

Official title:

Clinical Trial on Application of Injectable Recombinant Human Luteinizing Hormone (Luveris®) in the Treatment of Chinese Female Patients With Hypogonadotropic Hypogonadism: A Multi-center, Open, Prospective Drug Clinical Trial for Registration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01084265
• Other study ID #: IMP25345
• Status: Completed
• Phase: Phase 3
• First received: March 4, 2010
• Last updated: December 2, 2013
• Start date: February 2004
• Est. completion date: December 2005

Study information

• Verified date: December 2013
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2005
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypogonadism

Intervention

Drug:
• Recombinant human luteinizing hormone (r-hLH)
One r-hLH (75 International Units [IU]) injection s.c. once daily.
• Recombinant human follicle-stimulating hormone (r-hFSH)
One r-hFSH (150 IU) injection s.c. once daily.
• Human chorionic gonadotropin (hCG)
After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU hCG.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck Pte. Ltd., Singapore

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 14	Yes
Primary	Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter		Day 14	Yes
Primary	Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection		Day 14	Yes
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.	Day 14	Yes
Secondary	Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle		Day 14	No
Secondary	Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle		Day 14	No
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]).	up to Day 14	No
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.	Day 14	No
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.	Day 14	No