None listed
Conditions
Brief summary
Avastin (Registered Trademark) is currently used in many countries for the treatment of certain cancers. The primary purpose of this study is to investigate the similarities in the manner in which a new drug, DRL_BZ is distributed around the body compared with European approved and USA licensed Avastin. Who is it for? You may be eligible to join this study if you are a healthy male adult from 20 to 45 years of age with a BMI of 18.0 to 28.5 kg/m2 and body weight of 50 to 100kg. Participants enrolled in this study will be randomly allocated (by chance) to receive either the new DRL_BZ drug, USA licensed Avastin or European approved Avastin. All participants will receive a single dose which is adjusted for their weight. Participants will have a number of blood samples taken until Day 85 after the dose and will be monitored for side effects for 85 Days. It is hoped that the findings of this study will provide information regarding the similarity of drug distribution and safety of the new drug DRL_BZ compared to currently used Avastin for the treatment of certain types of cancer.
Interventions
Three Bevacizumab Preperations
Arm 1: DRL_BZ
100 mg in 4 mL - 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.
Arm 2: Avastin (Registered Trademark) United States-licenced (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1 time only Intravenous infusion.
Arm 3: Avastin (Registered Trademark) European Approved (bevacizumab)
100 mg in 4 mL- 1mg/kg
Recombinant humanised monoclonal antibody - bevacizumab
1
Three Bevacizumab Preperations Arm 1: DRL_BZ 100 mg in 4 mL - 1mg/kg Recombinant humanised monoclonal antibody - bevacizumab 1 time only Intravenous infusion. Arm 2: Avastin (Registered Trademark) United States-licenced (bevacizumab) 100 mg in 4 mL- 1mg/kg Recombinant humanised monoclonal antibody - bevacizumab 1 time only Intravenous infusion. Arm 3: Avastin (Registered Trademark) European Approved (bevacizumab) 100 mg in 4 mL- 1mg/kg Recombinant humanised monoclonal antibody - bevacizumab 1 time only Intravenous infusion. As the Infusion will be administered while the participants are inpatients of the facility, no strategy for adherence is required.
Sponsors
Dr Reddy’s Laboratories, Ltd (Biologics)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult male subjects, 20 to 45 years of age (inclusive) at the time of signing informed consent. 2. In general good health as determined by a qualified physician based on a comprehensive medical history, physical examination, and vital signs. 3. Have all Screening results (vital signs, physical examination, clinical laboratory tests, 12-lead electrocardiogram [ECG], and thyroid function) within the normal range or outside the normal range but assessed as clinically non-significant by the Investigator. 4. Body mass index between 18.0 and 28.5 kg/m2 (inclusive) and body weight of 50 to 100 kg (inclusive). 5. Subjects should be willing to abstain from sexual intercourse or be willing to use a condom in addition to having their female partner use another form of contraception (such as an intra-uterine device, barrier method with spermicide, oral contraceptive, injectable progesterone, sub-dermal implant) unless their partners are infertile or surgically sterile from the time of the first administration of the study drug until completion of study procedures and for a period of 7 months after administration of the study drug. 6. Capable and amenable to providing signed and dated informed consent to the study requirements. 7. Willing to stay on study restrictions for 4 months (7 months for contraception) from Screening.
Exclusion criteria
1. Positive test results for hepatitis B, hepatitis C, or human immunodeficiency virus-1 or -2. 2. Live virus vaccination within 3 months prior to Screening or intention to receive live virus vaccination during the study or up to 3 months after the administration of the study drug. 3. History of immunodeficiency or other clinically significant immunological disorders, auto-immune disorders, ongoing or frequent/recurring clinically significant infection defined as more than 3 events per year requiring treatment. 4. Any prior exposure to bevacizumab or vascular endothelial growth factor (VEGF) targeted treatment. 5. Prior exposure to any investigational monoclonal antibody within 12 months before enrolment. 6. Known allergy or hypersensitivity to Chinese hamster ovary cell products or to any recombinant human or humanised antibodies, other therapeutic proteins, or any excipients in the study formulations. 7. Abnormal and clinically relevant (in the opinion of the Investigator) ECG or corrected QT value (Fridericia correction) longer than 450 msec. 8. Blood donation in the 2 months before Screening. 9. Screening or admission to the study centre (Day -1) blood pressure higher than 160 mmHg (systolic) or higher than 100 mmHg (diastolic). For single measurements in the 140 to 160 mmHg range (systolic) or in the 90 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 less than or equal to 140 mmHg (systolic) and 90 mmHg (diastolic). 10. History of symptomatic orthostatic hypotension, fainting spells, syncope, or blackouts. 11. Fasting low density lipoprotein cholesterol higher than 160 mg/dL (or equivalent in mmol/L, 4.14 mmol/L) at Screening, or fasting triglycerides higher than 200 mg/dL (or equivalent in mmol/L, 2.26 mmol/L) at Screening or fasting glucose higher than 110 mg/dL (or equivalent in mmol/L, 6.11 mmol/L) at Screening. 12. Presence of any haemodynamically relevant abnormality or of any valvulopathy including mitral valve prolapse in the Screening echocardiography. 13. History of hypertension, angina, exertional dyspnoea, orthopnoea, congestive heart failure or myocardial infarction. 14. A history or current presence of clinically significant (in the opinion of the Investigator) atopic allergy (e.g., asthma including childhood asthma, urticaria, angioedema, eczematous dermatitis), hypersensitivity or allergic reactions (either spontaneous or following drug administration), including known or suspected clinically relevant drug hypersensitivity to any components of the study drug formulations, comparable drugs, or to latex. 15. Any history of thrombotic or embolic episodes or requirement for anticoagulation. 16. Any history of non-traumatic relevant haemorrhage, defined as any haemorrhage requiring medical intervention or any condition which may increase bleeding risk including coagulopathies or an international normalised ratio higher than 1.5. 17. History or presence of any clinically relevant (in the opinion of the Investigator) nervous system disease including, but not restricted to any stroke/transient ischaemic attack, migraine headaches or migrainous aura (scotoma with zig-zag lines or blinking lights) or of seizures (other than febrile seizures before the age of 5 years). 18. Significant family or personal history of intestinal inflammatory disease as well as personal history or current presence of gastrointestinal ulceration, bleeding or perforation, acute or chronic pancreatitis, and/or current gallbladder or bile duct disease. 19. Any intake of a non-steroidal anti-inflammatory drug including antiaggregant doses of aspirin in the last 2 weeks before administration of the study drug (non-steroidal anti-inflammatory drugs are forbidden until the last study visit) or marked constipation (less than 1 bowel movement every 3 days). 20. Any history of kidney disease, including, but not restricted to glomerulonephritis, minimum change nephropathy, and other renal diseases producing proteinuria, renal Fanconi syndrome, polycystic kidney disease, pyelonephritis or nephrolithiasis as well as history of nephrectomy. 21. History of and/or current gastrointestinal, endocrine, pulmonary, hepatic, psychiatric/neurological, cardiovascular, haematological (including pancytopenia, aplastic anaemia or blood dyscrasia), metabolic (including known diabetes mellitus), central nervous system disease, considered as significant by the Investigator. 22. Impaired liver function as determined by one of the following: a. Serum alanine aminotransferase and/or aspartate aminotransferase >1.5 x upper limit of normal (ULN) at Screening or admission to the study centre. Subjects with values between ULN and 1.5 x ULN may be included in the study if considered not clinically significant by the Investigator. b. Hepatic disease (e.g., cirrhosis) considered clinically significant by the Investigator. 23. Any clinically significant active infection, even if minor, ongoing at the time of Screening or study drug administration. 24. Presence of any non-healed wound or haematoma of a clinically relevant size (in the Investigator’s opinion), presence of any non-healed bone fracture at the time of Screening or administration of the study drug or increased accident risk due to professional or leisure time activities (e.g., motorcycle riding, martial arts) throughout the study participation. Subjects are expected to abstain from indulging in strenuous physical activity, outdoor contact sporting activities, which can possibly lead to any physical injury or trauma from 96 hours prior to the study drug administration until 8 weeks after the administration of the study drug. Early withdrawal subjects should also abstain from activities that carry an increased risk of injury until at least 8 weeks after the study drug administration. 25. Heparin sensitivity. 26. Any disorder that, in the Investigator’s opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures and limitations, such as history of chronic alcohol or drug abuse, significant endocrinological, respiratory, mental, or nervous disorder or other illness. 27. Participation in an interventional or Phase 1 study in the last 3 months, currently is on a follow-up visit schedule for any study, participation in more than 3 studies of experimental drug products in the past 12 months, or intake of an investigational drug in another study within 3 months or 5 half-lives (whichever is longer) prior to administration of the study drug in this study or planned intake of an investigational drug during the course of this study. 28. Any prior exposure (either due to treatment or to a research study) to bisphosphonates. 29. History of any cancer, including carcinoma in situ, lymphoma or leukaemia. 30. Major surgery within the past 12 months, major surgery planned within 12 months of study enrolment or any surgery including dental interventions planned within 3 months of study enrolment. 31. Current or former smoker or tested positive in the urine cotinine test at Screening or admission to the study centre. 32. History of alcohol abuse and/or inability to refrain from intake of alcoholic beverages from 48 hours prior to study drug administration and until Day 15 postdose or a positive alcohol breath test on Screening or admission to the study centre prior to study drug administration. 33. History of illegal drug abuse or abuse of medications or positive drug screen at Screening or admission to the study centre including urine tests for cotinine, amphetamines, barbiturates, cocaine, methadone, phencyclidine, 3, 4 methylenedioxymethamphetamine (ecstasy), tetrahydrocannabinol, and opiates. 34. Intake of prescribed or over-the-counter drugs (including acetaminophen) within less than 6 half-lives of the respective drug or herbal drugs within 28 days prior to study drug administration. 35. Legal incapacity or limited legal capacity. 36. Any person who is an employee of the Principal Investigator or study centre(s) with direct involvement in this proposed study or any other study under the direction of the Principal Investigator or the study centre or who is directly involved in the planning and/or conduct of the study, as well as close relatives of the employee, the Investigators, or the Sponsor.
Outcome results
None listed