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

This study has been completed.
Sponsor:
Collaborator:
Merck Pte. Ltd., Singapore
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01084265
First received: March 4, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Hypogonadism
Drug: Recombinant human luteinizing hormone (r-hLH)
Drug: Recombinant human follicle-stimulating hormone (r-hFSH)
Drug: Human chorionic gonadotropin (hCG)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Participants Who Met Both Index 1 and Index 2 [ Time Frame: Day 14 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 14 ] [ Designated as safety issue: Yes ]
  • Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection [ Time Frame: Day 14 ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Refused to Take hCG Injection [ Time Frame: Day 14 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Average Change of E2 Level in Participants Per Day up to Day 14 [ Time Frame: up to Day 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: February 2004
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Recombinant human luteinizing hormone (r-hLH)
    One r-hLH (75 International Units [IU]) injection s.c. once daily.
    Other Name: Luveris (r-hLH)
    Drug: Recombinant human follicle-stimulating hormone (r-hFSH)
    One r-hFSH (150 IU) injection s.c. once daily.
    Other Name: Gonal-F (r-hFSH)
    Drug: Human chorionic gonadotropin (hCG)
    After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU hCG.
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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01084265

Locations
China
Peking Union Medical College Hospital
Beijing, China, 100730
Sponsors and Collaborators
Merck KGaA
Merck Pte. Ltd., Singapore
Investigators
Study Director: Xin Li Merck Pte. Ltd., Singapore
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01084265     History of Changes
Other Study ID Numbers: IMP25345
Study First Received: March 4, 2010
Results First Received: February 6, 2012
Last Updated: December 2, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Merck KGaA:
Hypogonadism
Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant leutinizing hormone (r-hLH)

Additional relevant MeSH terms:
Hypogonadism
Gonadal Disorders
Endocrine System Diseases
Chorionic Gonadotropin
Hormones
Follicle Stimulating Hormone
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 26, 2014