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The Safety and Pharmacokinetics of Primapur and Gonal-f

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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Area Under Curve
Pharmacokinetics
Absorption
Interventions Drug: Follitropin alfa (Primapur)
Drug: Follitropin alfa (Gonal-F)
Enrollment 28
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Sequence A: Primapur - Gonal-F Sequence B: Gonal-F - Primapur
Hide Arm/Group Description 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. 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 Title: Period 1 (Primapur-Gonal-F)
Started 12 12
Completed 12 12
Not Completed 0 0
Period Title: Period 2 (Gonal-F-Primapur)
Started 12 12
Completed 12 12
Not Completed 0 0
Arm/Group Title Sequence A: Primapur - Gonal-F Sequence B: Gonal-F - Primapur Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 12 12 24
Hide Baseline Analysis Population Description
Women aged 18 to 40 years; body mass index (BMI) of 18.5 to 30 kg/m2
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Periods 1 and 2 Number Analyzed 12 participants 12 participants 24 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12
 100.0%
12
 100.0%
24
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 24 participants
29.92  (4.27) 26.58  (3.12) 28.25  (4.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
Female
12
 100.0%
12
 100.0%
24
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Russia Number Analyzed 12 participants 12 participants 24 participants
12
 100.0%
12
 100.0%
24
 100.0%
Body mass index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg per m2
Number Analyzed 12 participants 12 participants 24 participants
23.41  (3.53) 22.41  (2.80) 22.91  (3.16)
1.Primary Outcome
Title Area Under the Serum Concentration of Follicle Stimulating Hormone (FSH) - Time Curve (AUC(0-192))
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description:
All subjects who received a single subcutaneous injection of 300 IU Primapur.
All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Overall Number of Participants Analyzed 24 24
Geometric Mean (Standard Deviation)
Unit of Measure: mIU*h/ml
1202.85  (466.28) 1241.01  (418.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primapur, Gonal-F
Comments Statistical comparison of the obtained results comprised the calculation of parametric bilateral 90 % CIs for the ratios of the corresponding mean values of the pharmacokinetic parameters of the study and comparator drug. The equivalence of the pharmacokinetics of the drug products will be proven if the limits of the evaluated CIs for the ratios of the mean values are in the range of 80.00-125.00%.
Type of Statistical Test Equivalence
Comments The 90% CIs of the ratios of geometric means of log-transformed baseline AUC0-192 were used to assess bioequivalence between Primapur and Gonal-F (bioequivalence range of 80.00% to 125.00%)
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (%)
Estimated Value 93.31
Confidence Interval (2-Sided) 90%
87.25 to 99.79
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Serum Concentration of Follicle Stimulating Hormone (FSH) (Cmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description:
All subjects who received a single subcutaneous injection of 300 IU Primapur.
All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Overall Number of Participants Analyzed 24 24
Geometric Mean (Standard Deviation)
Unit of Measure: mIU/ml
14.32  (4.72) 16.00  (4.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primapur, Gonal-F
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments The 90% CIs of the ratios of geometric means of log-transformed baseline Cmax were used to assess bioequivalence between Primapur and Gonal-F (bioequivalence range of 80.00% to 125.00%)
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (%)
Estimated Value 87.93
Confidence Interval (2-Sided) 90%
82.85 to 93.33
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Reach a Maximum Follicle Stimulating Hormone (FSH) Serum Concentration (Tmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description:
All subjects who received a single subcutaneous injection of 300 IU Primapur.
All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Overall Number of Participants Analyzed 24 24
Mean (Standard Deviation)
Unit of Measure: hours
18.70  (5.77) 19.22  (4.93)
4.Secondary Outcome
Title Follicle Stimulating Hormone (FSH) Apparent Terminal Half-life (T1/2)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description:
All subjects who received a single subcutaneous injection of 300 IU Primapur.
All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Overall Number of Participants Analyzed 24 24
Geometric Least Squares Mean (Standard Deviation)
Unit of Measure: hours
70.78  (32.54) 71.71  (33.47)
5.Other Pre-specified Outcome
Title Elimination Rate Constant (Kel)
Hide Description 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.
Time Frame 0-192 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description:
All subjects who received a single subcutaneous injection of 300 IU Primapur.
All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
Overall Number of Participants Analyzed 24 24
Mean (Standard Deviation)
Unit of Measure: 1/h
0.01  (0.003) 0.01  (0.006)
Time Frame From the study day 1 to day 56.
Adverse Event Reporting Description 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).
 
Arm/Group Title Primapur Gonal-F
Hide Arm/Group Description All subjects who received a single subcutaneous injection of 300 IU Primapur. All subjects who received a single subcutaneous injection of 300 IU Gonal-F.
All-Cause Mortality
Primapur Gonal-F
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Primapur Gonal-F
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Primapur Gonal-F
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/24 (45.83%)      10/24 (41.67%)    
Gastrointestinal disorders     
Nausea  1  1/24 (4.17%)  1 1/24 (4.17%)  2
Vomiting  1  0/24 (0.00%)  0 1/24 (4.17%)  1
Investigations     
Laboratory investigations  1  8/24 (33.33%)  11 8/24 (33.33%)  11
Nervous system disorders     
Headache  1  2/24 (8.33%)  2 3/24 (12.50%)  3
1
Term from vocabulary, MedDRA 10.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: General Manager
Organization: IVFarma LLC
Phone: +7(499)6455342 ext 1
EMail: info@ivfarma.ru
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).
Layout table for additonal information
Responsible Party: IVFarma LLC
ClinicalTrials.gov Identifier: NCT03857230     History of Changes
Other Study ID Numbers: FSG-01-01
First Submitted: February 26, 2019
First Posted: February 27, 2019
Results First Submitted: March 13, 2019
Results First Posted: August 5, 2019
Last Update Posted: August 13, 2019