International Multicenter Randomized Double-blind Crossover Study of Pharmacokinetics, Pharmacodynamics and Tolerability of BCD-033 (CJSC BIOCAD, Russia) and Rebif® (Merck Serono S.p.А., Italy) After Single Subcutaneous Administration to Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Interferon beta-1a
- Conditions
- Healthy
- Sponsor
- Biocad
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Area Under Concentration-time Curve (AUC) of Interferon (IFN) Beta-1a From the Moment of Drug Administration Until 48 Hours and to Infinity(AUC(0-48) and AUC(0-∞) Respectively)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is a randomized double-blind crossover study of pharmacokinetics, pharmacodynamics and tolerability of BCD-033 (interferon beta-1a manufactured by CJSC BIOCAD, Russia) and Rebif® (Merck Serono S.p.A.., Italy) in healthy volunteers. The purpose of the study is to demonstrate the non-inferiority of pharmacokinetics, pharmacodynamics and tolerability parameters after single subcutaneous injection. Each dtug will be administered to each volunteer at a dose of 44 µg as a single subcutaneous injection with an interval of at least 14 days.
Detailed Description
Each dtug (BCD-033 and Rebif) will be administered to each volunteer at a dose of 44 µg as a single subcutaneous injection with an interval of at least 14 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent;
- •Male gender;
- •Age 18 - 45 years inclusive;
- •Body mass index (BMI) (18,5 - 24,99 kg/m2);
- •Healthy condition proven by the volunteer's history, global assessment and laboratory analysis results:
- •Absence in past medical history and at screening of clinically significant dysfunctions of circulatory, respiratory, nervous, hematopoietic, endocrine and digestive systems, liver and kidneys;
- •Haematology and biochemistry tests, urinalysis and thyroid hormone analysis results are within normal limits according to standards of the study site. Screening laboratory analyses should be performed not more than 14 days before volunteer's inclusion in the study;
- •Hemodynamic parameters are within normal limits: systolic blood pressure - from 100 to 139 mmHg, diastolic blood pressure - from 60 to 90 mmHg, heart rate - from 50 to 90 bpm;
- •Absence of history of chronic infection (tuberculosis) and chronic inflammation;
- •Absence of HIV, hepatitis B and C virus, syphilis;
Exclusion Criteria
- •Previous use of IFN-β1-containing medications at any time before inclusion;
- •History of serious allergic reactions (anaphylaxis or multiple allergy);
- •Known allergy or intolerance to interferons or any other components of study or reference drugs;
- •Major surgery within 30 days before screening;
- •Impossibility to install venous catheter for blood sampling (e.g. because of skin disorders at the sites of venipuncture);
- •Diseases or other conditions that can interfere with the investigational drugs pharmacokinetics (e.g. chronic liver, kidney, blood, circulatory system, lung or neuroendocrine diseases, including diabetes mellitus and others);
- •History of epileptic seizures;
- •Regular oral or parenteral use of any medications including over-the-counter drugs, vitamins and nutritional additives within less than 2 weeks before inclusion in the study;
- •Intake of medications, including over-the-counter drugs and biologically active additives that can influence hemodynamics, liver function etc. (barbiturates, omeprazole, cimetidine etc.) within less than 30 days before inclusion in the study;
- •Intake of medications that influence immune status (cytokines and their inductors, glucocorticoids etc.) within less than 30 days before participation in the study;
Arms & Interventions
BCD-033 → Rebif
Volunteers in this group initially will receive a single sc injection of the study drug BCD-033 (interferon beta-1a) at a dose of 44 µg (on Day 1) and then, after at least 14 days, a single sc injection of the reference drug Rebif® (interferon beta-1a) at a dose of 44 µg.
Intervention: Interferon beta-1a
Rebif → BCD-033
Volunteers in this group initially will receive a single sc injection of active comparator Rebif (interferon beta-1a) at a dose of 44 µg (on Day 1) and then, after at least 14 days, a single sc injection of the study drug BCD-033 (interferon beta-1a) at a dose of 44 µg.
Intervention: Interferon beta-1a
Outcomes
Primary Outcomes
Area Under Concentration-time Curve (AUC) of Interferon (IFN) Beta-1a From the Moment of Drug Administration Until 48 Hours and to Infinity(AUC(0-48) and AUC(0-∞) Respectively)
Time Frame: 0 to 48 hours post-dose
Primary outcome measure for pharmacokinetics analysis. Blood samples were taken before the injection, then after 15 min, 30 min, 45 min, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours.
Cmax of Interferon Beta-1a
Time Frame: 0 to 48 hours post-dose
Primary outcome measure for pharmacokinetics analysis Blood samples were taken before the injection, then after 15 min, 30 min, 45 min, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours.
AUC(0-168) and AUC(0-∞) of Neopterin and MxA Protein
Time Frame: 0 to 168 hours post-dose
Primary outcome measure for pharmacodynamics analysis. Blood samples were taken before the injection, then after 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours.
Secondary Outcomes
- AE of Garde 3-4 Incidence(up to Day 43)
- Тmax of Interferon Beta-1a Blood Samples Were Taken Before the Injection, Then After 15 Min, 30 Min, 45 Min, 1 Hour, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours and 48 Hours.(0 to 48 hours post-dose)
- Т½ of Interferon Beta-1a Blood Samples Were Taken Before the Injection, Then After 15 Min, 30 Min, 45 Min, 1 Hour, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours and 48 Hours.(0 to 48 hours post-dose)
- Кel of Interferon Beta-1a Blood Samples Were Taken Before the Injection, Then After 15 Min, 30 Min, 45 Min, 1 Hour, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours and 48 Hours.(0 to 48 hours post-dose)
- Cl of Interferon Beta-1a Blood Samples Were Taken Before the Injection, Then After 15 Min, 30 Min, 45 Min, 1 Hour, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours and 48 Hours.(0 to 48 hours post-dose)
- Cmax of Neopterin and MxA Protein Blood Samples Were Taken Before the Injection, Then After 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 Hours.(0 to 168 hours post-dose)
- Tmax of Neopterin and MxA Protein(0 to 168 hours post-dose)
- Adverse Event (AE) and Serious Adverse Event (SAE) Incidence(up to Day 43)
- Local Reaction Incidence(up to Day 43)
- Study Withdrawal Rate Due to AE(up to Day 43)