Pergoveris FD and Liquid China BE Study

Healthy Clinical Trial

Official title:

A Phase I, Open-label, Randomized, Three-period, Crossover, Single-center Trial to Assess the Bioequivalence of the Co-administration of 900 IU of Follitropin Alfa (Gonal-f) and 450 IU of Lutropin Alfa (Luveris) Versus the Fixed Combination of 900 IU Follitropin Alfa and 450 IU Lutropin Alfa in Pergoveris, Administered SC as Liquid and FD Formulation, in Pituitary Suppressed Healthy Premenopausal Female Chinese Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04899193
• Other study ID #: MS200061_0012
• Status: Completed
• Phase: Phase 1
• Start date: May 8, 2021
• Est. completion date: May 28, 2022

Study information

• Verified date: June 2022
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess the bioequivalence (BE) of the fixed combination of follitropin alfa and lutropin alfa in Pergoveris freeze-dried (FD) (Test 1) or in Pergoveris Liquid (Test 2) versus the co-administration of Gonal-f and Luveris (Reference), administered subcutaneously (SC) in pituitary suppressed, healthy premenopausal Chinese female participants, at the doses of 900 international unit (IU) of follitropin alfa and 450 IU lutropin alfa.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: May 28, 2022
• Est. primary completion date: May 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and ECG, blood pressure (systolic and diastolic) and pulse rate

• Participants who have a negative serum pregnancy test before starting Marvelon and on the days before the Pergoveris or Gonal-f/Luveris dose

• Participants who are taking an oral contraceptive pill (OCP) for at least 1 month prior to Screening and are willing to take the combined oral contraceptive pill (COCP) during the study and to recommence taking their own OCP from Day 55 after the first Pergoveris or Gonal-f/Luveris dosing

• Participants with normal baseline follicle stimulating hormone (FSH) (< 12 IU/L) and estradiol (E2) levels [<= 100 picograms per millilitre (pg/mL)] and showing follicle size <= 11 millimeter (mm)

• Participants who had a normal Thinprep cytologic test (TCT) within the last 1 year before Screening (timeframe to be adjusted based on local routine clinical care). If not performed in routine clinical care, participant must be willing to undergo a cervical smear at Screening

• Participants who have a body weight within >= 45 kilogram (kg) and body mass index within the range 18.5 to 29.9 kilogram per meter square (kg/m^2) (inclusive)

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants with any condition that, in the Investigator's opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation

• Participants with clinically significant abnormalities of the genital organs as determined by gynecological examination and Trans Vaginal Ultrasound Scan (TVUS) and based on the Investigator's judgment (example., ovarian tumors, non-functional ovarian cysts, endometrial hyperplasia)

• Participants with polycystic ovaries as defined by at least 1 of the following 2 criteria fulfilled: More than 12 follicles < 10 mm mean diameter in either ovary or at least one ovary of > 10 mL volume

• Participants with ovarian follicle-like structures larger than 11 mm (at Screening)

• Participants with positive result for syphilis, human immunodeficiency virus, hepatitis B surface antigen or hepatitis C Virus

• Participants using drugs that may reduce the effectiveness of COCP (e.g., phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate,rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole, and herbal remedies containing Hypericum perforatum [St. John's Wort])

• Participation in any clinical study within 3 months or 5 half-lives, whichever is longer, prior to Screening or during participation Unsuccessful downregulation, demonstrated by serum luteinising hormone (LH) or FSH levels > 2.0 IU/L or E2 levels > 100 pg/mL the day before Pergoveris or Gonal-f/Luveris administration, or showing follicle size > 11 mm

• Participants vaccinated with any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2) vaccine within 4 weeks before administration of study intervention (Marvelon)

• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Pergoveris FD
Participants will be administered with 900 IU of recombinant human follicle-stimulating hormone (r-hFSH) and 450 IU of recombinant human luteinizing hormone (r-hLH) freeze-dried powder (Freeze-dried Pergoveris) as subcutaneous injection on Day 1 in investigation period 1 or investigation period 2 or investigation period 3. There will be a washout period of 6 days between investigation period 1 and investigation period 2 and 17 days between investigation period 2 and investigation period 3.
• Pergoveris Liquid
Participants will be administered with 900 IU of r-hFSH and 450 IU of r-hLH solution (Pergoveris Liquid) as subcutaneous injection using disposable pen-injector on Day 1 in investigation period 1 or investigation period 2 or investigation period 3. There will be a washout period of 6 days between investigation period 1 and investigation period 2 and 17 days between investigation period 2 and investigation period 3.
• Gonal-f
Participants will be administered with 900 IU of folitropin alfa (Gonal-f) as subcutaneous injection on Day 1 in investigation period 1 or investigation period 2 or investigation period 3. There will be a washout period of 6 days between investigation period 1 and investigation period 2 and 17 days between investigation period 2 and investigation period 3.
• Luveris
Participants will be administered with 450 IU of lutropin alfa (Luveris) as subcutaneous injection on Day 1 in investigation period 1 or investigation period 2 or investigation period 3. There will be a washout period of 6 days between investigation period 1 and investigation period 2 and 17 days between investigation period 2 and investigation period 3.

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Sampling Time After Administration (AUC0-t, adj) of Follitropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Primary	Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Sampling Time After Administration (AUC0-t, adj) of Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Primary	Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf,adj) of Follitropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Primary	Baseline Adjusted Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-inf,adj) of Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Primary	Baseline Adjusted Maximum Observed Serum Concentration (Cmax,adj) of Follitropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Primary	Baseline Adjusted Maximum Observed Serum Concentration (Cmax,adj) of Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Secondary	Number of Participants with Clinically Significant Changes From Baseline in Laboratory Parameters		Baseline up to Day 55
Secondary	Number of Participants with Clinically Significant Changes From Baseline in Vital Signs		Baseline up to Day 55
Secondary	Number of Participants with Clinically Significant Changes From Baseline in Electrocardiogram (ECGs) Findings		Baseline up to Day 55
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)		Baseline up to Day 55
Secondary	Absolute Value and Change From Baseline in Serum Estradiol Levels		Baseline, Day 14 and 39
Secondary	Change From Baseline in Follicle Size Assessed by Trans Vaginal Ultrasound Scan		Baseline, Day 8, 14, 22, 39 and 55
Secondary	Change From Baseline in Follicle Number Assessed by Trans Vaginal Ultrasound Scan		Baseline, Day 8, 14, 22, 39 and 55
Secondary	Number of Participants With Local Tolerability/Injection Site Reactions (ISRs)		At 5 minutes and 1, 2, 4, 6, 12 and 24 hours post-dose
Secondary	Time to Reach the Maximum Observed Serum Concentration (Tmax) of Follitropin Alfa and Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Secondary	Apparent Terminal Half-Life (T1/2) of Follitropin Alfa and Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period
Secondary	Apparent Terminal Elimination Rate Constant (Lambda z) of Follitropin Alfa and Lutropin Alfa		Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 72, 96, 120 and 168 hours post-dose in each period

External Links

•   Trial Awareness and Transparency website