NCT03857230

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2015

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 29, 2015

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 10, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 10, 2016

Completed
2.8 years until next milestone

First Submitted

Initial submission to the registry

February 26, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 27, 2019

Completed
5 months until next milestone

Results Posted

Study results publicly available

August 5, 2019

Completed
Last Updated

August 13, 2019

Status Verified

August 1, 2019

Enrollment Period

6 months

First QC Date

February 26, 2019

Results QC Date

March 13, 2019

Last Update Submit

August 5, 2019

Conditions

Area Under CurvePharmacokineticsAbsorption

Keywords

follitropin alfafollicle stimulating hormonehormones, hormone substitutes, and hormone antagonistsphysiological effects of drugsbiosimilarbioequivalence

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (2)

  • Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax)

    0-192 hours

  • Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2)

    0-192 hours

Other Outcomes (1)

  • Elimination Rate Constant (Kel)

    0-192 hours

Study Arms (2)

Sequence A: Primapur - Gonal-F

EXPERIMENTAL

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)Drug: Follitropin alfa (Gonal-F)

Sequence B: Gonal-F - Primapur

ACTIVE COMPARATOR

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)Drug: Follitropin alfa (Gonal-F)

Interventions

Follitropin alfa (Primapur)DRUG

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.

Also known as: Follitropin alpha, Follitropin
Sequence A: Primapur - Gonal-FSequence B: Gonal-F - Primapur
Follitropin alfa (Gonal-F)DRUG

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.

Also known as: Follitropin alpha, Follitropin
Sequence A: Primapur - Gonal-FSequence B: Gonal-F - Primapur

Eligibility Criteria

Age18 Years - 40 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy female volunteers aged 18 to 40 years.
  • Body mass index (BMI) of 18.5 to 30.0 kg/m2.
  • Subjects who have used oral contraceptives for at least 2 menstrual cycles before study entry.
  • Regular menstruation cycle (24 to 35 days) before initiation of oral contraception.
  • Presence of both ovaries.
  • Subjects who are negative for drugs of abuse and alcohol tests at screening.
  • Subjects who are healthy as validated by pre study medical history, physical examination.
  • Subjects with acceptable clinical laboratory test results.
  • 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.
  • Ability to comply with the requirements of the protocol.
  • 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.

You may not qualify if:

  • Hypersensitivity to follitropin alpha, combined oral contraceptive (ethinylestradiol and drospirenone) or excipients.
  • Allergy, angioedema (hereditary or idiopathic) in history.
  • Previous history of ovarian hyperstimulation syndrome (OHSS).
  • Inability to establish a venous catheter for blood sampling.
  • Presence of polycystic ovaries (PCO) and ovarian cysts.
  • Neoplasia and a history of malignant disease.
  • Deep vein thrombosis, pulmonary embolism.
  • Subjects with impaired thyroid function.
  • 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).
  • 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.
  • Cardiovascular, bronchopulmonary, nervous, endocrine systems, gastrointestinal tract, liver, kidney, hematopoietic, immune systems, mental diseases.
  • Acute infectious diseases less than 4 weeks before the start of the study.
  • 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.
  • Blood donation less than 3 months before the start of the study.
  • Participation in clinical studies of drugs less than 3 months before the start of the present study.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

O.M. Filatov Municipal Clinical Hospital N 15

Moscow, Russia

Location

Related 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 volunteers. Eksperimental'naya i Klinicheskaya Farmakologiya. 2017; 80(4): 13-17 (in Russian).

    RESULT

Related Links

MeSH Terms

Interventions

follitropin alfaGlycoprotein Hormones, alpha SubunitFollicle Stimulating Hormone

Intervention Hierarchy (Ancestors)

Chorionic GonadotropinGonadotropinsPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsGonadotropins, PituitaryLuteinizing HormonePituitary Hormones, AnteriorPituitary HormonesThyrotropinPlacental HormonesPeptidesAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
General Manager
Organization
IVFarma LLC
info@ivfarma.ru
+7(499)6455342

Study Officials

  • Ivan G Gordeev, D.Sc., MD

    O.M. Filatov Municipal Clinical Hospital N 15

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

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

February 26, 2019

First Posted

February 27, 2019

Study Start

October 29, 2015

Primary Completion

May 10, 2016

Study Completion

May 10, 2016

Last Updated

August 13, 2019

Results First Posted

August 5, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share

Locations

RU(1)