Area Under CurvePhase 1NCT03857230
The Safety and Pharmacokinetics of Primapur and Gonal-f
A Phase 1 study testing Follitropin alfa (Primapur) and Follitropin alfa (Gonal-F) in people with Area Under Curve and Pharmacokinetics, run by IVFarma LLC at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Area Under Curve, Pharmacokinetics, Absorption
- What is being tested?
- Follitropin alfa (Primapur) and Follitropin alfa (Gonal-F)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteRussia
- Study dates
- 29 Oct 2015to 10 May 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
- Smoking more than 5 cigarettes/day.
- Narcomania, alcoholism.
- Presence of pregnancy.
- Lactating.
- Any reason that, in the opinion of the investigator, could interfere with safety of the subject or interfere with the objectives of the study.
- Subjects with a lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Safety, Tolerance and Pharmacokinetics of Primapur and Gonal-f Upon Single-dose Subcutaneous Administration in Healthy Volunteers
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.
Read the detailed description
A Phase I, prospective, randomized, open-label, crossover, 2-period, two treatment, clinical study in healthy female volunteers.
Objectives of the study:
- 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.
- To determine the AUC0-t value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the T½ value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the Сmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the Tmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To compare the obtained pharmacokinetic characteristics of Primapur and Gonal-F.
- Conditions
- Area Under Curve, Pharmacokinetics, Absorption
- Being tested
- Follitropin alfa (Primapur), Follitropin alfa (Gonal-F)
- Keywords
- follitropin alfa, follicle stimulating hormone, hormones, hormone substitutes, and hormone antagonists, physiological effects of drugs, biosimilar, bioequivalence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follitropin alfa (Primapur)Drug
Also called Follitropin alpha, Follitropin
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)Drug
Also called Follitropin alpha, Follitropin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Follitropin alfa (Primapur); Drug: Follitropin alfa (Gonal-F) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 0-192 hours
Secondary outcomes (2)
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.
Measured: 0-192 hours
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.
Measured: 0-192 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2019
- Study start29 Oct 2015
- Primary completion10 May 2016
- Study completion10 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Area Under CurveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- IVFarma LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- NADIM LLC
- Responsible party
- Sponsor
- Investigators
- Ivan G Gordeev, D.Sc., MD, Principal investigator, O.M. Filatov Municipal Clinical Hospital N 15
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03857230
- Sponsor's protocol ID
- FSG-01-01
- Status last verified
- Aug 2019
- First submitted
- 26 Feb 2019
- Last updated
- 13 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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).
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Safety, Tolerance and Pharmacokinetics of Primapur and Gonal-f Upon Single-dose Subcutaneous Administration in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03857230
- Acronym / sponsor ID
- FSG-01-01
- Conditions
- Area Under Curve, Pharmacokinetics, Absorption
- Keywords
- follitropin alfa, follicle stimulating hormone, hormones, hormone substitutes, and hormone antagonists, physiological effects of drugs, biosimilar, bioequivalence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- IVFarma LLCIndustry (pharma, biotech, devices)
- Collaborators
- NADIM LLC
- Study start
- 29 Oct 2015 (actual)
- Primary completion
- 10 May 2016 (actual)
- Study completion
- 10 May 2016 (actual)
- First posted
- 27 Feb 2019 (actual)
- Results
- Posted 5 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A Phase I, prospective, randomized, open-label, crossover, 2-period, two treatment, clinical study in healthy female volunteers.
Objectives of the study:
- 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.
- To determine the AUC0-t value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the T½ value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the Сmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To determine the Tmax value of Primapur following a single 300 IU subcutaneous injection to healthy volunteers.
- To compare the obtained pharmacokinetic characteristics of Primapur and Gonal-F.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A: Primapur - Gonal-F | Experimental | Drug: Follitropin alfa (Primapur), Drug: Follitropin alfa (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. |
| Sequence B: Gonal-F - Primapur | Active comparator | Drug: Follitropin alfa (Primapur), Drug: Follitropin alfa (Gonal-F)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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Follitropin alfa (Primapur)Also: Follitropin alpha, FollitropinDuring 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. | Drug | Sequence A: Primapur - Gonal-F, Sequence B: Gonal-F - Primapur |
| Follitropin alfa (Gonal-F)Also: Follitropin alpha, FollitropinDuring 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. | Drug | Sequence A: Primapur - Gonal-F, Sequence B: Gonal-F - Primapur |
Primary outcome
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.
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.
2 secondary outcomes
Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax)
Time frame: 0-192 hours
Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2)
Time frame: 0-192 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationTyul'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).
- Link to a publisher site with a full-text articleLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivan G Gordeev, D.Sc., MD principal investigator
O.M. Filatov Municipal Clinical Hospital N 15
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Follitropin alfa (Primapur) and Follitropin alfa (Gonal-F) in people with Area Under Curve and Pharmacokinetics, run by IVFarma LLC at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Serum Concentration of Follicle Stimulating Hormone (FSH) - Time Curve (AUC(0-192)) (time frame: 0-192 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03857230, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.