Trial Outcomes & Findings for The Safety and Pharmacokinetics of Primapur and Gonal-f (NCT NCT03857230)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

0-192 hours

Results posted on

2019-08-13

Participant Flow

Duration of participation was about 73 days: screening period (up to 7 days), preparation period (up to 28 days), the 1st period (9 days), the 2nd period (9 days), and the follow-up period (28 days starting from the first day of the 2nd period). The wash-out period is 10 days.

28 healthy female volunteers aged 18 to 40 years inclusively have been enrolled according to the inclusion and non-inclusion criteria, among them 4 back-ups enrolled in the study to replace the volunteers excluded before the study completion.

Participant milestones

Participant milestones
Measure	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.	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.
Period 1 (Primapur-Gonal-F) STARTED	12	12
Period 1 (Primapur-Gonal-F) COMPLETED	12	12
Period 1 (Primapur-Gonal-F) NOT COMPLETED	0	0
Period 2 (Gonal-F-Primapur) STARTED	12	12
Period 2 (Gonal-F-Primapur) COMPLETED	12	12
Period 2 (Gonal-F-Primapur) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Safety and Pharmacokinetics of Primapur and Gonal-f

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence A: Primapur - Gonal-F n=12 Participants 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 a single subcutaneous injection of 300 IU Gonal-F.	Sequence B: Gonal-F - Primapur n=12 Participants 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 a single subcutaneous injection of 300 IU Primapur.	Total n=24 Participants Total of all reporting groups
Age, Categorical Periods 1 and 2 · <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Periods 1 and 2 · Between 18 and 65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical Periods 1 and 2 · >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	29.92 years STANDARD_DEVIATION 4.27 • n=5 Participants	26.58 years STANDARD_DEVIATION 3.12 • n=7 Participants	28.25 years STANDARD_DEVIATION 4.04 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Russia	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Body mass index (BMI)	23.41 kg per m2 STANDARD_DEVIATION 3.53 • n=5 Participants	22.41 kg per m2 STANDARD_DEVIATION 2.80 • n=7 Participants	22.91 kg per m2 STANDARD_DEVIATION 3.16 • n=5 Participants

PRIMARY outcome

Timeframe: 0-192 hours

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Primapur n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Area Under the Serum Concentration of Follicle Stimulating Hormone (FSH) - Time Curve (AUC(0-192))	1202.85 mIU*h/ml Standard Deviation 466.28	1241.01 mIU*h/ml Standard Deviation 418.61

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Primapur n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Maximum Serum Concentration of Follicle Stimulating Hormone (FSH) (Cmax)	14.32 mIU/ml Standard Deviation 4.72	16.00 mIU/ml Standard Deviation 4.88

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Primapur n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax)	18.70 hours Standard Deviation 5.77	19.22 hours Standard Deviation 4.93

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Primapur n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2)	70.78 hours Standard Deviation 32.54	71.71 hours Standard Deviation 33.47

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Primapur n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 Participants All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Elimination Rate Constant (Kel)	0.01 1/h Standard Deviation 0.003	0.01 1/h Standard Deviation 0.006

Adverse Events

Primapur

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Gonal-F

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Primapur n=24 participants at risk All subjects who received a single subcutaneous injection of 300 IU Primapur.	Gonal-F n=24 participants at risk All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Investigations Laboratory investigations	33.3% 8/24 • Number of events 11 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).	33.3% 8/24 • Number of events 11 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).
Nervous system disorders Headache	8.3% 2/24 • Number of events 2 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).	12.5% 3/24 • Number of events 3 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).
Gastrointestinal disorders Nausea	4.2% 1/24 • Number of events 1 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).	4.2% 1/24 • Number of events 2 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).
Gastrointestinal disorders Vomiting	0.00% 0/24 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).	4.2% 1/24 • Number of events 1 • From the study day 1 to day 56. An adverse event was defined as any adverse event that began following the first dose of follitropin alfa administration till the end of follow-up period. Adverse events were reported from the 1st period (9 days), wash out period (10 days), 2nd period (9 days) and follow-up period (28 days).

Additional Information

General Manager

IVFarma LLC

Phone: +7(499)6455342

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place