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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
28
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.
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.
O.M. Filatov Municipal Clinical Hospital N 15
Moscow, Russia
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.
Time frame: 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.
Time frame: 0-192 hours
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.
Time frame: 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.
Time frame: 0-192 hours
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