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Trial record 84 of 101 for:    ETHINYL ESTRADIOL AND DROSPIRENONE

The Safety and Pharmacokinetics of Primapur and Gonal-f

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03857230
Recruitment Status : Completed
First Posted : February 27, 2019
Results First Posted : August 5, 2019
Last Update Posted : August 13, 2019
Sponsor:
Collaborator:
NADIM LLC
Information provided by (Responsible Party):
IVFarma LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Area Under Curve Pharmacokinetics Absorption Drug: Follitropin alfa (Primapur) Drug: Follitropin alfa (Gonal-F) Phase 1

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Study of Safety, Tolerance and Pharmacokinetics of Primapur and Gonal-f Upon Single-dose Subcutaneous Administration in Healthy Volunteers
Actual Study Start Date : October 29, 2015
Actual Primary Completion Date : May 10, 2016
Actual Study Completion Date : May 10, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Sequence A: Primapur - Gonal-F
Subjects were randomly assigned to receive treatment sequence A: single subcutaneous injection of 300 IU Primapur on study day 1, after 10 days of wash out period a single subcutaneous injection of 300 IU Gonal-F.
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.

Other Names:
  • Follitropin alpha
  • Follitropin

Drug: 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.

Other Names:
  • Follitropin alpha
  • Follitropin

Active Comparator: Sequence B: Gonal-F - Primapur
Subjects were randomly assigned to receive treatment sequence B: single subcutaneous injection of 300 IU Gonal-F on study day 1, after 10 days of wash out period a single subcutaneous injection of 300 IU Primapur.
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.

Other Names:
  • Follitropin alpha
  • Follitropin

Drug: 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.

Other Names:
  • Follitropin alpha
  • Follitropin




Primary Outcome Measures :
  1. Area Under the Serum Concentration of Follicle Stimulating Hormone (FSH) - Time Curve (AUC(0-192)) [ Time Frame: 0-192 hours ]

    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.


  2. Maximum Serum Concentration of Follicle Stimulating Hormone (FSH) (Cmax) [ Time Frame: 0-192 hours ]
    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.


Secondary Outcome Measures :
  1. Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax) [ Time Frame: 0-192 hours ]
    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.

  2. Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2) [ Time Frame: 0-192 hours ]
    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.


Other Outcome Measures:
  1. Elimination Rate Constant (Kel) [ Time Frame: 0-192 hours ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03857230


Locations
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Russian Federation
O.M. Filatov Municipal Clinical Hospital N 15
Moscow, Russian Federation
Sponsors and Collaborators
IVFarma LLC
NADIM LLC
Investigators
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Principal Investigator: Ivan G Gordeev, D.Sc., MD O.M. Filatov Municipal Clinical Hospital N 15
  Study Documents (Full-Text)

Documents provided by IVFarma LLC:

Additional Information:
Publications of Results:
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 volunteers. Eksperimental'naya i Klinicheskaya Farmakologiya. 2017; 80(4): 13-17 (in Russian).

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Responsible Party: IVFarma LLC
ClinicalTrials.gov Identifier: NCT03857230     History of Changes
Other Study ID Numbers: FSG-01-01
First Posted: February 27, 2019    Key Record Dates
Results First Posted: August 5, 2019
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IVFarma LLC:
follitropin alfa
follicle stimulating hormone
hormones, hormone substitutes, and hormone antagonists
physiological effects of drugs
biosimilar
bioequivalence
Additional relevant MeSH terms:
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Hormones
Follicle Stimulating Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs