Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03857230
Other study ID # FSG-01-01
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date October 29, 2015
Est. completion date May 10, 2016

Study information

Verified date August 2019
Source IVFarma LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of the current phase I study was to establish bioequivalence, safety, and tolerance of single 300 IU subcutaneous dose of follitropin alfa biosimilar (Primapur) in comparison to that of reference follitropin alfa preparation (Gonal-F) in healthy young female volunteers.


Description:

A Phase I, prospective, randomized, open-label, crossover, 2-period, two treatment, clinical study in healthy female volunteers.

Objectives of the study:

1. To evaluate the frequency and severity of adverse events (AE) following a single 300 IU subcutaneous injection of Primapur (IVFarma, LLC, Russia) and Gonal-F (Merck Serono S.p.A., Italy) to healthy volunteers.

2. To determine the AUC0-t value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.

3. To determine the T½ value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.

4. To determine the Сmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.

5. To determine the Tmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.

6. To compare the obtained pharmacokinetic characteristics of Primapur and Gonal-F.


Recruitment information / eligibility

Status Completed
Enrollment 28
Est. completion date May 10, 2016
Est. primary completion date May 10, 2016
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 40 Years
Eligibility Inclusion Criteria:

1. Healthy female volunteers aged 18 to 40 years.

2. Body mass index (BMI) of 18.5 to 30.0 kg/m2.

3. Subjects who have used oral contraceptives for at least 2 menstrual cycles before study entry.

4. Regular menstruation cycle (24 to 35 days) before initiation of oral contraception.

5. Presence of both ovaries.

6. Subjects who are negative for drugs of abuse and alcohol tests at screening.

7. Subjects who are healthy as validated by pre study medical history, physical examination.

8. Subjects with acceptable clinical laboratory test results.

9. A signed informed consent form that confirms in writing the volunteer's consent to participate in this clinical study and the volunteer's willingness to comply with all physician recommendations and protocol limitations for the time of participation in the clinical study.

10. Ability to comply with the requirements of the protocol.

11. Participants in the study, as well as their sexual partners, are knowledgeable and willing to voluntarily, starting from the week before being included in the study and up to 4 weeks after the last dose of the study drug, and in addition to the contraceptive used, use at least 1 barrier contraceptive method or spermicide.

Exclusion Criteria:

1. Hypersensitivity to follitropin alpha, combined oral contraceptive (ethinylestradiol and drospirenone) or excipients.

2. Allergy, angioedema (hereditary or idiopathic) in history.

3. Previous history of ovarian hyperstimulation syndrome (OHSS).

4. Inability to establish a venous catheter for blood sampling.

5. Presence of polycystic ovaries (PCO) and ovarian cysts.

6. Neoplasia and a history of malignant disease.

7. Deep vein thrombosis, pulmonary embolism.

8. Subjects with impaired thyroid function.

9. Regular usage or administration of any drugs, including non-prescription drugs, vitamins, homeopathic remedies and dietary supplements, less than 2 weeks before the study (with the exception of contraceptive pills).

10. Admission less than 2 months before the start of the study of drugs that have a pronounced effect on hemodynamics, liver function, and medication contained follicle stimulating hormone (FSH), luteinizing hormone (LH), chorionic gonadotropin (hCG), clomiphene, gonadotropin-releasing hormone (GnRH) analogues.

11. Cardiovascular, bronchopulmonary, nervous, endocrine systems, gastrointestinal tract, liver, kidney, hematopoietic, immune systems, mental diseases.

12. Acute infectious diseases less than 4 weeks before the start of the study.

13. Systolic pressure less than 100 mm or above 130 mm Hg; diastolic pressure less than 70 mm or above 90 mm Hg; heart rate less than 60 or more than 80 beats/min.

14. Blood donation less than 3 months before the start of the study.

15. Participation in clinical studies of drugs less than 3 months before the start of the present study.

16. More than 5 alcohol units per week (1 unit is equal to 50 ml of a strong alcoholic drink, 200 ml of dry wine or 500 ml of beer) or anamnestic information about alcoholism, drug addiction, drug abuse.

17. Smoking more than 5 cigarettes/day.

18. Narcomania, alcoholism.

19. Presence of pregnancy.

20. Lactating.

21. Any reason that, in the opinion of the investigator, could interfere with safety of the subject or interfere with the objectives of the study.

22. Subjects with a lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Follitropin alfa (Primapur)
During the crossover pharmacokinetic phase, after 42 days of combined oral contraceptive (ethinylestradiol and drospirenone) administration subjects with endogenous level of follicle stimulating hormone (FSH) less than 5 IU/l were randomly assigned to receive one of the following treatment sequences: Sequence A: Single subcutaneous injection of 300 IU Primapur on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Gonal-F. Sequence B: Single subcutaneous injection of 300 IU US Gonal-F on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Primapur.
Follitropin alfa (Gonal-F)
During the crossover pharmacokinetic phase, after 42 days of combined oral contraceptive (ethinylestradiol and drospirenone) administration subjects with endogenous level of follicle stimulating hormone (FSH) less than 5 IU/l were randomly assigned to receive one of the following treatment sequences: Sequence A: Single subcutaneous injection of 300 IU Primapur on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Gonal-F. Sequence B: Single subcutaneous injection of 300 IU US Gonal-F on study day 1, after 10 days of wash out a single subcutaneous injection of 300 IU Primapur.

Locations

Country Name City State
Russian Federation O.M. Filatov Municipal Clinical Hospital N 15 Moscow

Sponsors (2)

Lead Sponsor Collaborator
IVFarma LLC NADIM LLC

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

Tyul'kina EE, Gordeev IG, Grebenkin DYu, Kazei VA, Tsikarishvili MM, Luchinkina EE, et al. Randomized crossover comparative study of safety, tolerance and pharmacokinetics of Primapur vs. Gonal-f upon single-dose subcutaneous administration in healthy vol

Outcome

Type Measure Description Time frame Safety issue
Other Elimination Rate Constant (Kel) Elimination rate constant (Kel): Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. 0-192 hours
Primary Area Under the Serum Concentration of Follicle Stimulating Hormone (FSH) - Time Curve (AUC(0-192)) Area under curve (AUC), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose.
Blood samples to study the pharmacokinetics are to be collected via a venous catheter, which is placed by means of vein puncture before any injection of r-hFSH. Blood sampling were carried out at certain time points according to the specified scheme: - 20 minutes (20 minutes before the drug injection), 0 hours (immediately prior to injection), and 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168, and 192 hours after each injection of the drug product.
0-192 hours
Primary Maximum Serum Concentration of Follicle Stimulating Hormone (FSH) (Cmax) Maximum serum concentration (Cmax), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. 0-192 hours
Secondary Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax) Time to reach a maximum serum concentration (Tmax), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. 0-192 hours
Secondary Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2) Terminal half-life (T1/2), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. 0-192 hours
See also
  Status Clinical Trial Phase
Completed NCT04092725 - Study to Evaluate the Effect of SCY-078 on the PK of Dabigatran in Healthy Subjects Phase 1
Completed NCT04181008 - Pharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers Early Phase 1
Active, not recruiting NCT03258151 - Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
Completed NCT04406415 - Oral Nafamostat in Healthy Volunteers Phase 1
Not yet recruiting NCT05421312 - Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip Phase 4
Completed NCT02534753 - A Pharmacokinetics Study of Intravenous Ascorbic Acid Phase 1
Completed NCT01636024 - To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of Inhaled AZD7594 Phase 1
Completed NCT01976078 - Development of Voriconazole Pharmacokinetics and Metabolism in Children and Adolescents N/A
Completed NCT01682408 - Assess Pharmacokinetics of Fostamatinib in Fed and Fasted State in Combination With Ranitidine to Assess Bioavailability Phase 1
Completed NCT01208155 - Study in Healthy Males to Assess Bioavailability of 4 Different Fostamatinib Tablets Phase 1
Completed NCT01415102 - A First In Human Study In Healthy People To Evaluate Safety, Toleration And Time Course Of Plasma Concentration Of Single Inhaled Doses Of PF-05212372. Phase 1
Completed NCT01214941 - Effect of Itraconazole and Ticlopidine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol Phase 4
Completed NCT01260025 - Tolerability and Pharmacokinetics of M2ES in the Treatment of Advanced Solid Tumor Phase 1
Completed NCT01055964 - a Comparative Pharmacokinetic Study of Two Oral Formulations of Tacrolimus in Renal Allograft Recipients Phase 3
Completed NCT00730145 - A Single Dose Study Investigating The Elimination Of PD-0332334 In Patients Receiving Regular Hemodialysis Phase 1
Completed NCT00984009 - A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice Phase 1
Completed NCT00747721 - Pharmacokinetics of Dexmedetomidine During Prolonged Infusion in ICU Phase 1
Completed NCT00983242 - Drug-Drug Interaction Between Colchicine and Verapamil ER Phase 1
Completed NCT01276119 - The First Clinical Study to Test Safety, Blood Levels and Other Effects of CDP6038 in Healthy Males Phase 1
Completed NCT00746499 - Pharmacokinetic Study of Raltegravir in Healthy Premenopausal Women. Phase 1