Clinical trial NCT04605107: Biosimilarity Study of IM Injection of Human Chorionic Gonadotrophin After Parenteral Administration of Treatment A TEST Product Epifasi 5000 I.U. Ampoules (EIPICO PHARMA, EGYPT) and Treatment B REFERENCE Product Pregnyl 5000 I.U. Ampoules (Baxter Pharmaceutical Solutions for Organon, USA).
Official title: Comparative Randomized, Single Dose, Parallel, Triple-blinded Study in Infertile Females to Evaluate Biosimilarity of IM Injection of Human Chorionic Gonadotrophin After Parenteral Administration of Treatment A TEST Product Epifasi 5000 I.U. Ampoules (EIPICO PHARMA, EGYPT) and Treatment B REFERENCE Product Pregnyl 5000 I.U. Ampoules (Baxter Pharmaceutical Solutions for Organon, USA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility, Female
Lead sponsor: Genuine Research Center, Egypt
Sponsor class: INDUSTRY
Collaborators: name: EIPICO PHARMA, EGYPT
First posted: 2020-10-27
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Comparative randomized, single dose, parallel, triple-blinded study in infertile females to evaluate biosimilarity of IM Injection of Human Chorionic Gonadotrophin (HCG) after Parenteral administration of Treatment A TEST Product Epifasi 5000 I.U. Ampoules (EIPICO PHARMA, EGYPT) and Treatment B REFERENCE Product Pregnyl 5000 I.U. Ampoules (Baxter Pharmaceutical Solutions for Organon, USA)

Detailed description: In this study, the biosimilarity of Human chorionic gonadotropin (HCG) from Epifasi IM Injection (EIPICO Pharma Egypt) and Pregnyl IM Injection (Baxter Pharmaceutical Solutions for Organon, USA) after a single IM dose administration of each to healthy adult will be investigated to determining the study variables: Ovarian Ultrasonic counting mature grafian follicles, Number of retrieved oocytes and their grades.

Eligibility criteria: Inclusion Criteria:

1. Premenopausal woman between 18 - 40 years of age.
2. Body mass index (BMI) of 32 or less.
3. A menstrual cycle lasting between 21 and 35 days.
4. Serum hormone levels of FSH 12 IU/L or less, PRL 1040 mIU/L or less, and TSH within the normal range of 0.3- 4.9 mIU/L
5. Patient having both ovaries and a normal uterine cavity confirmed by hysteroscopy, or hysterosalpingography.
6. All patients had to be infertile due to at least one of the following causes and must have justified ART (Assisted Reproductive Technology) treatment: tubal factor, mild endometriosis (American Fertility Society classification stage I orII), unexplained infertility, or male factor
7. Patients achieving good ovarian response and considered to receive hCG for final follicular maturation prior to OPU.
8. Written and signed informed consent by the patient.
9. Subject does not have allergy to the drugs under investigation.
10. Medical demographics without evidence of clinically significant deviation from rather normal medical condition.

Exclusion Criteria:

1. Patients with low ovarian reserve, as proved by hormonal assays and basal antral follicular count.
2. More than three previous assisted reproductive technology cycle or treatment with clomiphene citrate or gonadotropins for at least 1 month before screening,
3. Patients with pelvic abnormality that would interfere with ovarian accessibility for OPU, e.g. ovarian endometriotic cysts or high and retro-uterine ovary.
4. Patients not achieving a satisfactory ovarian response on ovulation induction, whether poor response (3 or less mature ovarian follicles) or over-response with high likelihood of developing ovarian hyperstimulation syndrome (OHSS) on triggering with HCG.
5. History of hypersensitivity to the study medications or to drugs with similar chemical structure.
6. Patients unlikely to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and likelihood of not completing the study.
7. Mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study.
8. Results of laboratory tests which are clinically significant.
9. Acute infection within one week preceding first study drug administration.
10. History of drug or alcohol abuse.
11. Subject does not agree not to take any prescription or non-prescription drugs within two weeks before first study drug administration and until the end of the study.
12. Subject is on a special diet (for example subject is vegetarian).
13. Subject does not agree not to consume any beverages or foods containing methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to the study administration of either study period until donating the last sample in each respective period.
14. Subject does not agree not to consume any beverages or foods containing grapefruit 7 days prior to first study drug administration until the end of the study.
15. Subject has a history of severe diseases which have direct impact on the study.
16. Participation in a biosimilarity study or in a clinical study within the last 6 weeks before first study drug administration.
17. Subject intends to be hospitalized within 3 months after first study drug administration.

Primary outcomes:
measure: No. of mature follicles
timeFrame: Up to 34-36 hours post dose
Secondary outcomes:
measure: Safety Evaluation
timeFrame: the patient is observed during the whole course of the study and for one month post study
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Genuine Research Center GRC
Study officials:
affiliation: Genuine Research Center
name: Ahmed Elshafeey, Ph.D. Pharma
role: STUDY_DIRECTOR
References:
citation: Steinijans VW, Diletti E. Statistical analysis of bioavailability studies: parametric and nonparametric confidence intervals. Eur J Clin Pharmacol. 1983;24(1):127-36. doi: 10.1007/BF00613939.
citation: Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
citation: Driscoll GL, Tyler JP, Hangan JT, Fisher PR, Birdsall MA, Knight DC. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation. Hum Reprod. 2000 Jun;15(6):1305-10. doi: 10.1093/humrep/15.6.1305.