Hypogonadotropic HypogonadismPhase 4NCT00328926
Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
A Phase 4 study testing Luveris® 75 IU, Luveris® 25 IU and Recombinant human follicle stimulating hormone (r-hFSH) in people with Hypogonadotropic Hypogonadism, run by EMD Serono at 1 site in United States.
Trial summary
Sponsor has decided to discontinue Luveris® in the United States (US) due to level of customer demand for this product, and not due to any efficacy or safety concerns. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Hypogonadotropic Hypogonadism
- What is being tested?
- Luveris® 75 IU, Luveris® 25 IU and Recombinant human follicle stimulating hormone (r-hFSH)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to May 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Be premenopausal, between 18 and 40 years of age inclusive on the day of consent
- Have a clinical history of hypogonadotropic hypogonadism (World health organization [WHO] Group I type of anovulation) on the basis of congenital or acquired hypothalamic or pituitary endocrine dysfunction in the presence of qualifying screening laboratories
- Have no prior treatment cycles with gonadotropins or gonadotropin releasing hormone (GnRH) (gonadotropin naïve)
- Have discontinued estrogen-progesterone replacement therapy at least one month before the screening procedure
- Have primary or secondary amenorrhea
- Have a negative progestin challenge test performed during Screening
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- Have the following hormonal values in a centrally analyzed fasting blood sample, drawn within 6 weeks before initiation of treatment:
- Follicle-Stimulating Hormone (FSH): less than (<)5 international unit per liter (IU/L)
- Leutinizing hormone (LH): <1.2 IU/L (a second Baseline serum LH level will be repeated two weeks after the initial LH draw)
- Prolactin: < 43.3 nanogram per milliliter (ng/mL) (<1040 milli-international unit per liter [mIU/L])
- Thyroid Stimulating Hormone (TSH): <6.5 micro-international units per milliliter (mcIU/mL)
- Free Thyroxin (T4): 0.8-1.8 nanogram per deciliter (ng/dL) (11-24 picomole per liter [pmol/L])
- Testosterone: <1.0 ng/mL (<3.5 nanomole per liter [nmol/L])
- Have an endovaginal pelvic ultrasound scan showing (i) no clinically significant uterine abnormality, (ii) no ovarian tumor or cyst, and (iii) less than or equal to (=<)13 small follicles (mean diameter =<10 milliliter [mm]) on the largest section through each ovary
- Have a normal cervical pap smear within 6 months of the initial visit
- Where indicated, have a normal or unchanged computed tomography (CT) scan or nuclear magnetic resonance (NMR) scan of the hypothalamic pituitary region on file
- Have a body mass index (BMI) between 18.4 and 31.4 kilogram per square meter (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 not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care
Who cannot join
- Any medical condition which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug
- Any pre-existing medical condition which would compromise the subject's ability to conceive in vivo or to successfully complete a pregnancy
- Ongoing pregnancy
- Clinically important systemic disease (example: insulin-dependent diabetes mellitus, epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular disease, serious corticoid-dependent asthma)
- Known infection with human immunodeficiency virus (HIV), Hepatitis B or C
- Ovarian enlargement or cyst of unknown etiology
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- 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
- Exercise program exceeding 10 hours per week
- Is planning to undergo in vitro fertilization, intracytoplasmic sperm injection or another assisted reproductive technology (ART) procedure, other than intrauterine insemination, in the course of a study treatment cycle
- Currently undergoing treatment with psychotropic medication or with any other medication known to interfere with normal reproductive function (example: neuroleptics, dopamine antagonists)
Trial locations and contacts
1 site in 1 country.
United States1 site
U.S. Medical Information, 1-888-275-7376
Rockland, Massachusetts, 02370
About this study
Official title: A Phase IV, Multicenter, Randomized, Double-blinded, Clinical Trial to Confirm the Efficacy of the 75 IU Dose of Luveris® vs. Placebo When Administered With Follitropin Alfa for Induction of Follicular Development and Pregnancy in Hypogonadotropic Hypogonadal Women With Profound LH Deficiency, as Defined by a Baseline LH Level <1.2 IU/L
Sponsor has decided to discontinue Luveris® in the United States (US) due to level of customer demand for this product, and not due to any efficacy or safety concerns.
Read the detailed description
To confirm the efficacy of the 75 IU dose of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of clinical pregnancy in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L), and to study the efficacy of a lower dose (25 IU) of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of follicular development in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L).
- Conditions
- Hypogonadotropic Hypogonadism
- Being tested
- Luveris® 75 IU, Luveris® 25 IU, Placebo, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant human chorionic gonadotropin (r-hCG)
- Keywords
- Hypogonadotropic Hypogonadism (LH <1.2 IU/L), Placebo, Luveris® 75 IU, Luveris® 25 IU, Recombinant human chorionic gonadotropin (r-hCG)
- Medical subject headings
- Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Luveris® 75 IUDrug
Also called Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)
Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 75 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and estradiol [E2] levels). Total duration will be of 3 treatment cycles.
Luveris® 25 IUDrug
Also called Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)
Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 25 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
PlaceboDrug
Placebo will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Recombinant human follicle stimulating hormone (r-hFSH)Drug
Also called Follitropin alfa
Fixed dose of recombinant human follicle stimulating hormone (r-hFSH, follitropin alfa) 75 to 150 IU will be administered subcutaneously for 7 days. After 7 days of treatment, if the subject response will suboptimal, based on follicular growth and serum E2 levels, follitropin alfa dose adjusted to maximal dose of 225 IU. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
Recombinant human chorionic gonadotropin (r-hCG)Drug
Also called Choriogonadotropin alfa
When the follicular response will adequate, ovulation will be triggered by a single 250 microgram subcutaneous injection of recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa). Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles.
| Study group | Role | What they receive |
|---|---|---|
| Luveris® 75 IU | Active comparator | Not described Receives: Drug: Luveris® 75 IU; Drug: Recombinant human follicle stimulating hormone (r-hFSH); Drug: Recombinant human chorionic gonadotropin (r-hCG) |
| Luveris® 25 IU | Active comparator | Not described Receives: Drug: Luveris® 25 IU; Drug: Recombinant human follicle stimulating hormone (r-hFSH); Drug: Recombinant human chorionic gonadotropin (r-hCG) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo; Drug: Recombinant human follicle stimulating hormone (r-hFSH); Drug: Recombinant human chorionic gonadotropin (r-hCG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Clinical Pregnancy
Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination.
Measured: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
Secondary outcomes (2)
Percentage of Participants With Cumulative Clinical Pregnancy
Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. Cumulative clinical pregnancy referred to all clinical pregnancy that occurred during all the 3 treatment cycles.
Measured: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
Percentage of Participants With Cumulative Ovulation
Ovulation was defined as a mid-luteal phase progesterone (P4) level greater than or equal to (>=) 10 nanogram per milliliter (ng/mL). Cumulative ovulation referred to all ovulations that occurred during all the 3 treatment cycles.
Measured: Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2006 (estimated)
- Study startMar 2006
- Primary completionMay 2012
- Study completionMay 2012
Why it stopped: Please see "Purpose" statement
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypogonadotropic HypogonadismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00328926
- Sponsor's protocol ID
- 26109
- Status last verified
- Aug 2013
- First submitted
- 20 May 2006
- Last updated
- 7 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Multicenter, Randomized, Double-blinded, Clinical Trial to Confirm the Efficacy of the 75 IU Dose of Luveris® vs. Placebo When Administered With Follitropin Alfa for Induction of Follicular Development and Pregnancy in Hypogonadotropic Hypogonadal Women With Profound LH Deficiency, as Defined by a Baseline LH Level <1.2 IU/L
- ClinicalTrials.gov ID
- NCT00328926
- Acronym / sponsor ID
- 26109
- Conditions
- Hypogonadotropic Hypogonadism
- Keywords
- Hypogonadotropic Hypogonadism (LH <1.2 IU/L), Placebo, Luveris® 75 IU, Luveris® 25 IU, Recombinant human chorionic gonadotropin (r-hCG)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Please see "Purpose" statement
- Enrolment
- 11 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 24 May 2006 (estimated)
- Results
- Posted 12 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sponsor has decided to discontinue Luveris® in the United States (US) due to level of customer demand for this product, and not due to any efficacy or safety concerns.
Detailed description
To confirm the efficacy of the 75 IU dose of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of clinical pregnancy in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L), and to study the efficacy of a lower dose (25 IU) of Luveris® compared to placebo when administered concomitantly with follitropin alfa for induction of follicular development in women with hypogonadotropic hypogonadism and profound LH deficiency (LH <1.2 IU/L).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Luveris® 75 IU | Active comparator | Drug: Luveris® 75 IU, Drug: Recombinant human follicle stimulating hormone (r-hFSH), Drug: Recombinant human chorionic gonadotropin (r-hCG) |
| Luveris® 25 IU | Active comparator | Drug: Luveris® 25 IU, Drug: Recombinant human follicle stimulating hormone (r-hFSH), Drug: Recombinant human chorionic gonadotropin (r-hCG) |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Recombinant human follicle stimulating hormone (r-hFSH), Drug: Recombinant human chorionic gonadotropin (r-hCG) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Be premenopausal, between 18 and 40 years of age inclusive on the day of consent
- Have a clinical history of hypogonadotropic hypogonadism (World health organization [WHO] Group I type of anovulation) on the basis of congenital or acquired hypothalamic or pituitary endocrine dysfunction in the presence of qualifying screening laboratories
- Have no prior treatment cycles with gonadotropins or gonadotropin releasing hormone (GnRH) (gonadotropin naïve)
- Have discontinued estrogen-progesterone replacement therapy at least one month before the screening procedure
- Have primary or secondary amenorrhea
Key exclusion criteria (13 listed)
- Any medical condition which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug
- Any pre-existing medical condition which would compromise the subject's ability to conceive in vivo or to successfully complete a pregnancy
- Ongoing pregnancy
- Clinically important systemic disease (example: insulin-dependent diabetes mellitus, epilepsy, serious migraine, intermittent purpura, hepatic, renal or cardiovascular disease, serious corticoid-dependent asthma)
- Known infection with human immunodeficiency virus (HIV), Hepatitis B or C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Luveris® 75 IUAlso: Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 75 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and estradiol [E2] levels). Total duration will be of 3 treatment cycles. | Drug | Luveris® 75 IU |
| Luveris® 25 IUAlso: Lutropin alfa, Recombinant human luteinizing hormone (r-hLH)Recombinant human luteinizing hormone (r-hLH, lutropin alfa, Luveris®), 25 IU will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles. | Drug | Luveris® 25 IU |
| PlaceboPlacebo will be administered subcutaneously once daily. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles. | Drug | Placebo |
| Recombinant human follicle stimulating hormone (r-hFSH)Also: Follitropin alfaFixed dose of recombinant human follicle stimulating hormone (r-hFSH, follitropin alfa) 75 to 150 IU will be administered subcutaneously for 7 days. After 7 days of treatment, if the subject response will suboptimal, based on follicular growth and serum E2 levels, follitropin alfa dose adjusted to maximal dose of 225 IU. Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles. | Drug | Luveris® 25 IU, Luveris® 75 IU, Placebo |
| Recombinant human chorionic gonadotropin (r-hCG)Also: Choriogonadotropin alfaWhen the follicular response will adequate, ovulation will be triggered by a single 250 microgram subcutaneous injection of recombinant human chorionic gonadotropin (r-hCG, choriogonadotropin alfa). Duration of treatment cycle will be up to 14 days, or maximum of 21 days (if follicular maturation is imminent, based upon follicular growth and E2 levels). Total duration will be of 3 treatment cycles. | Drug | Luveris® 25 IU, Luveris® 75 IU, Placebo |
Primary outcome
Time to Clinical Pregnancy
Time frame: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination.
2 secondary outcomes
Percentage of Participants With Cumulative Clinical Pregnancy
Time frame: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
Percentage of Participants With Cumulative Ovulation
Time frame: Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days])
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Full FDA approved prescribing information can be found hereLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Serono S.A., Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Luveris® 75 IU, Luveris® 25 IU and Recombinant human follicle stimulating hormone (r-hFSH) in people with Hypogonadotropic Hypogonadism, run by EMD Serono at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Clinical Pregnancy (time frame: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2013.