None listed
Conditions
Brief summary
This study aims to investigate the safety of new formulation of bevacizumab called CBT124 and bioequivalence when compared to two already marketed formulations, one approved in US and other in EU. Who is it for? You may be eligible to join this study if you are an adult healthy male aged 18 to 50 years (inclusive). Study details Participants will be randomised (allocated by chance) to either a test formulation or one of the two marketed formulations of bevacizumab. Drugs will be administered intravenously once only. The study will compare the safety, tolerability, pharmacokinetics (PK) (the levels of drug in the blood), pharmacodynamics (PD) (what the drug does to the body) and immunogenicity (body’s immune response) of the three drugs. In order to measure this, blood samples will be collected at various points after treatment has been given.
Interventions
Investigational Medicinal Product: CBT124 (Cipla BioTech bevacizumab) drug product is presented as a sterile solution containing 100 mg bevacizumab. Prior to administration, bevacizumab will be diluted to the required volume using 0.9% sodium chloride solution.
CBT124 will be supplied as 100 mg per 4 mL; a single dose of 1 mg per kg will be administered over-a-period of 90 minute intravenous infusion.
Reference products: EU-Avastin(Registered Trademark) will be supplied as 100 mg per 4 mL; a sin
Investigational Medicinal Product: CBT124 (Cipla BioTech bevacizumab) drug product is presented as a sterile solution containing 100 mg bevacizumab. Prior to administration, bevacizumab will be diluted to the required volume using 0.9% sodium chloride solution. CBT124 will be supplied as 100 mg per 4 mL; a single dose of 1 mg per kg will be administered over-a-period of 90 minute intravenous infusion. Reference products: EU-Avastin(Registered Trademark) will be supplied as 100 mg per 4 mL; a single dose of 1 mg per kg will be administered over-a-period of 90 minute intravenous infusion. US-Avastin(Registered Trademark) will be supplied as 100 mg per 4 mL; a single dose of 1 mg per kg will be administered over-a-period of 90 minute intravenous infusion. Additional information, including the formulation, appearance, batch numbers, reconstitution and administration details will be included in a separate Pharmacy Manual
Sponsors
Cipla BioTec Pvt. Ltd.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
Male
Age
15 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
*Adult healthy male subjects aged 18 to 50 years (inclusive) and between 18.0 and 30.0 kg per sq mtr body mass index (inclusive) and body weight between 60 kg and 100 kg, both inclusive. *Subjects who are healthy as determined by pre-study medical history, physical examination, vital signs and 12 lead electrocardiogram (ECG) at screening and admission. Subjects whose clinical laboratory test results are normal, or where outside the reference range is judged as not clinically relevant by the Investigator. *Have systolic blood pressure between 140 and 90 mmHg both inclusive, diastolic blood pressure 90 and 50 mmHg both inclusive and heart rate 40 and 90 bpm both inclusive at screening and admission. For single measurements in the 141 to 160 mmHg range (systolic) or in the 91 to 100 mmHg range (diastolic), a single repetition on a the same day is allowed and, in this case, the mean of both measurements will guide eligibility. The mean of both the measurements should be 140 mmHg (systolic) and 90 mmHg (diastolic) both inclusive. *Have physical examination results without clinically relevant findings at screening and admission. *Have 12-lead ECG results without clinically relevant findings at screening and admission. *Subjects who are non-smokers and have not regularly used tobacco or nicotine containing products for at least 3 months preceding screening and have a less than 10 pack year smoking history. *Males must be willing to use a medically acceptable method of contraception from the time of the administration of investigational product (IP), throughout the study and for a period of 6 months after the administration of the IP. Medically acceptable methods of contraception include the following: abstinence; or willing to use a condom in addition to having their female partner use another form of contraception such as an intra-uterine device, oral contraceptive, injectable progesterone, sub-dermal implant, or a tubal ligation. This requirement may be waived if the Principal Investigator or delegate is satisfied that the subject or subject’s female partner is sterile i.e. if female has undergone hysterectomy or tubal ligation at least 3 months prior to screening or is post-menopausal (no period for at least 12 months prior to screening) or if the subject has undergone vasectomy at least 6 months prior to screening. *Must agree not to donate sperm for at least 6 months after the administration of IP. *Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures including standardized meal. *Must be able to provide informed consent which must be obtained prior to any study related procedures. *Subjects who have a negative fecal occult blood test and a negative Helicobacter pylori stool antigen test. *Subjects who are willing to comply with the study restrictions, and comply with the scheduled visits from screening and throughout the study.
Exclusion criteria
*Have a history of hypersensitivity or allergic reactions (either spontaneous or following drug administration) to bevacizumab or vascular endothelial growth factor (VEGF) targeted treatment or to any of the excipients. *Have a history of or presence of current clinically significant gastrointestinal (including diverticulitis, stomach ulcers, inflammatory intestinal disease, gastrointestinal perforations/fistulae/intra-abdominal abscess), any other internal, non gastrointestinal fistulae that is at an increased risk of bleeding), renal, hepatic, cardiovascular, hematological (including pancytopenia, aplastic anaemia or blood dyscrasia), pulmonary, neurologic, metabolic (including known diabetes mellitus), psychiatric or allergic disease excluding mild asymptomatic seasonal allergies. *Have a history of and/or current cardiac disease defined as one of the following: *History of congestive heart failure; *Angina pectoris requiring anti-anginal medication; *Evidence of transmural infarction on ECG; *History of sustained hypertension (systolic greater than 180 mmHg and/or diastolic greater than 100 mmHg) or hypertensive crisis or hypertension encephalopathy; *Clinically significant valvular heart disease; or *Severe arterial thromboembolic events. *Have a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus, or human immunodeficiency virus (HIV) I and II at screening. *Have a history of cancer including lymphoma, leukaemia and skin cancer (including any history of malignancy, even resected basal cell carcinoma or squamous cell carcinoma). *Have an illness within 30 days prior to screening, or prior to dosing, that is classed as clinically significant by the Investigator. *Prior exposure to any investigational monoclonal antibody within 12 months of study drug administration. *Any clinically significant infection, in the opinion of the Investigator, ongoing at screening or admission to the clinical unit. *Have had major surgery within 30 days prior to screening, or will have an operation between screening and the end of study visit, or still has an unhealed wound, including wound dehiscence and wound healing complications requiring medical intervention. *Have received live vaccine(s) within 30 days prior to screening or will require a live vaccine(s) between screening and the end of study visit. *Have an intake of alcoholic beverages of more than 28 units per week (1 unit = 250 mL of beer, 25 mL of spirits or one glass [125 mL] of wine). *Have reasonable evidence (in the opinion of the Investigator) of drug abuse as indicated by a positive urinary drug test at screening or admission. *Have taken medication with a half-life of more than 24 hours within 30 days or less than 10 half-lives of the medication prior to the administration of the study drug as determined by the Investigator. *Have donated more than 100 mL blood within 4 weeks prior to the administration of the study drug. Blood donation and blood products is not permitted throughout study. *Have participated in another clinical study of an investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the administration of the study drug, or are currently participating in another clinical study of an investigational drug, or intending to participate in another clinical study of an investigational drug before completion of all scheduled evaluations in this clinical study. *Subjects who, in the opinion of the Investigator, are not likely to complete the study for whatever reason. *The Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff directly involved in the conduct of the clinical study or any of their relatives. *Abnormal or irregular bowel movements e.g., less than 1 bowel movement every 3 days. *Any history of non-traumatic hemorrhage (i.e. any hemorrhage requiring medical intervention) or any condition which may increase bleeding risk including clotting disorders, thrombocytopenia (platelet count less than 150, 000 per micro L) or an international normalized ratio higher than 1.5 at screening. *Impaired liver function as determined by: *Serum alanine aminotransferase and/or aspartate aminotransferase more than 1.5 times upper limit of normal (ULN) at screening or admission. Subjects with values between ULN and 1.5 times ULN may be included in the study if considered not clinically significant by the Investigator. *Any intake of a non-steroidal anti-inflammatory drug (NSAID) including any dose of aspirin in the 30 days before administration of the study drug (NSAIDs are not allowed for the duration of the study). *Intake of herbal drugs or dietary supplements excluding routine vitamins but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 30 days prior to study drug administration, unless agreed as not clinically relevant by the Investigator and Sponsor. *Consumption of any foods containing poppy seeds within 48 hours prior to screening and admission to the clinical center. *Strenuous exercise or activity within 96 hours prior to admission to the clinical center and has a creatinine kinase value is more than 2.5 times upper limit of normal. *Subjects with unsuitable veins for infusion or venipuncture. *Subjects with a non-healing wound or hematoma of a clinically relevant size as assessed by the Investigator, or a clinically significant current fracture. *Presence of proteinuria (other than trace amounts) at screening or admission. *Personal history of venous thromboembolic events or idiopathic venous thromboembolic events in first degree relatives. *Inability to refrain from contact or collision sport until Day 30.
Outcome results
None listed