Pergoveris FD and Liquid China BE Study

NCT04899193 | Completed Phase 1

• 1 other identifier: MS200061_0012
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Healthy; Pergoveris; Bioequivalence; Infertility

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (11)

• Number of Participants with Clinically Significant Changes From Baseline in Laboratory Parameters

  Baseline up to Day 55

• Number of Participants with Clinically Significant Changes From Baseline in Vital Signs

  Baseline up to Day 55

• Number of Participants with Clinically Significant Changes From Baseline in Electrocardiogram (ECGs) Findings

  Baseline up to Day 55

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  Baseline up to Day 55

• Absolute Value and Change From Baseline in Serum Estradiol Levels

  Baseline, Day 14 and 39

Study Arms (6)

Sequence 1: First Reference, Then Test 1, Then Test 2

EXPERIMENTAL

Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Sequence 2: First Test 1, Then Test 2, Then Reference

EXPERIMENTAL

Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Sequence 3: First Test 2, Then Reference, Then Test 1

EXPERIMENTAL

Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Sequence 4: First Reference, Then Test 2, Then Test 1

EXPERIMENTAL

Participants will receive single dose of Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 1 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 2 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Sequence 5: First Test 1, Then Reference, Then Test 2

EXPERIMENTAL

Participants will receive single dose of Test 1 drug (Pergoveris FD) on Day 1 in investigation period 1 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 2 followed by Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Sequence 6: First Test 2, Then Test 1, Then Reference

EXPERIMENTAL

Participants will receive single dose of Test 2 drug (Pergoveris Liquid) on Day 1 in investigation period 1 followed by Test 1 drug (Pergoveris FD) on Day 1 in investigation period 2 followed by Reference drug (Gonal-f/Luveris injection) on Day 1 in investigation period 3. A washout period of 6 days will be maintained between period 1 and 2 and washout period of 17 days will be maintained between period 2 and 3.

Drug: Pergoveris FD; Drug: Pergoveris Liquid; Drug: Gonal-f; Drug: Luveris

Interventions

Pergoveris FD DRUG

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.

Sequence 1: First Reference, Then Test 1, Then Test 2; Sequence 2: First Test 1, Then Test 2, Then Reference; Sequence 3: First Test 2, Then Reference, Then Test 1; Sequence 4: First Reference, Then Test 2, Then Test 1; Sequence 5: First Test 1, Then Reference, Then Test 2; Sequence 6: First Test 2, Then Test 1, Then Reference

Pergoveris Liquid DRUG

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.

Sequence 1: First Reference, Then Test 1, Then Test 2; Sequence 2: First Test 1, Then Test 2, Then Reference; Sequence 3: First Test 2, Then Reference, Then Test 1; Sequence 4: First Reference, Then Test 2, Then Test 1; Sequence 5: First Test 1, Then Reference, Then Test 2; Sequence 6: First Test 2, Then Test 1, Then Reference

Gonal-f DRUG

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.

Sequence 1: First Reference, Then Test 1, Then Test 2; Sequence 2: First Test 1, Then Test 2, Then Reference; Sequence 3: First Test 2, Then Reference, Then Test 1; Sequence 4: First Reference, Then Test 2, Then Test 1; Sequence 5: First Test 1, Then Reference, Then Test 2; Sequence 6: First Test 2, Then Test 1, Then Reference

Luveris DRUG

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.

Sequence 1: First Reference, Then Test 1, Then Test 2; Sequence 2: First Test 1, Then Test 2, Then Reference; Sequence 3: First Test 2, Then Reference, Then Test 1; Sequence 4: First Reference, Then Test 2, Then Test 1; Sequence 5: First Test 1, Then Reference, Then Test 2; Sequence 6: First Test 2, Then Test 1, Then Reference

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Xuanwu Hospital, Capital Medical University

Beijing, 100053, China

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Infertility

Interventions

follitropin alfa; Luteinizing Hormone, beta Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: May 24, 2021
• Study Start: May 8, 2021
• Primary Completion: May 28, 2022
• Study Completion: May 28, 2022
• Last Updated: June 15, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)