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

Primary Purpose

Hypogonadism

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Recombinant human luteinizing hormone (r-hLH)
Recombinant human follicle-stimulating hormone (r-hFSH)
Human chorionic gonadotropin (hCG)
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadism focused on measuring Hypogonadism, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant leutinizing hormone (r-hLH)

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Peking Union Medical College Hospital

Outcomes

Primary Outcome Measures

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.
Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter
Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection
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.

Secondary Outcome Measures

Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle
Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle
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]).
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.
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.

Full Information

First Posted
March 4, 2010
Last Updated
December 2, 2013
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Pte. Ltd., Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT01084265
Brief Title
A Study Using Recombinant Human Luteinizing Hormone (r-hLH, Luveris®) in the Treatment of Chinese Women With Hypogonadotropic Hypogonadism
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
December 2005 (Actual)
Study Completion Date
December 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Pte. Ltd., Singapore

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism
Keywords
Hypogonadism, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant leutinizing hormone (r-hLH)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Recombinant human luteinizing hormone (r-hLH)
Other Intervention Name(s)
Luveris (r-hLH)
Intervention Description
One r-hLH (75 International Units [IU]) injection s.c. once daily.
Intervention Type
Drug
Intervention Name(s)
Recombinant human follicle-stimulating hormone (r-hFSH)
Other Intervention Name(s)
Gonal-F (r-hFSH)
Intervention Description
One r-hFSH (150 IU) injection s.c. once daily.
Intervention Type
Drug
Intervention Name(s)
Human chorionic gonadotropin (hCG)
Intervention Description
After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU hCG.
Primary Outcome Measure Information:
Title
Number of Participants Who Met Both Index 1 and Index 2
Description
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
Title
Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter
Time Frame
Day 14
Title
Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection
Time Frame
Day 14
Title
Number of Participants Who Refused to Take hCG Injection
Description
Participant refused to take hCG injection for the concern of OHSS or the participant was pregnant.
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
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
Title
Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle
Time Frame
Day 14
Title
Average Change of E2 Level in Participants Per Day up to Day 14
Description
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
Title
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies
Description
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
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xin Li
Organizational Affiliation
Merck Pte. Ltd., Singapore
Official's Role
Study Director
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100730
Country
China

12. IPD Sharing Statement

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

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