Phase I - Pharmacokinetic Comparability Study in Healthy Male Volunteers

Mylan

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: EU marketed Avastin(R); Drug: US marketed Avastin(R); Drug: MYL-1402O

Study type: Interventional

Funder types: Industry

Identifiers

NCT02469987

MYL-1402O-1002

2014-005621-12 (EudraCT Number)

Details and patient eligibility

About

Double-blind, single-dose, three-treatment, parallel group design PK comparability study of MYL-1402O solution manufactured for Mylan compared to US and EU marketed Avastin® solution (bevacizumab).

Full description

Double-blind, single-dose, three-treatment, parallel group design PK comparability study of MYL-1402O solution manufactured for Mylan compared to US and EU marketed Avastin® solution (bevacizumab) in a total of 111 healthy, adult male volunteers (37 subjects per treatment arm). After randomization, subjects will receive one of the following treatments: A single 1 mg/kg dose administered by i.v. infusion (25 mL over approximately 90 minutes) of MYL-1402O, an equivalent i.v. infusion of US marketed Avastin® (1 mg/kg), or an equivalent i.v. infusion of EU marketed Avastin® (1 mg/kg).

Enrollment: 111 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Males aged 18-55 yrs. (inclusive)
• BMI: 19.0 to 30.0 kg/m2 (inclusive)
• Weight: ≥ 60kg and ≤100kg
• Subjects should be willing to use adequate contraception and not donate sperm from admission to clinical research center until 6 months post dosing.
• All intermittent medications should have be stopped at least 14days prior to admission to the clinical research center.
• All intermittent non topical medication must be stopped at least 30days prior to admission to the clinical research center.
• Ability and willingness to abstain from ETOH 48hrs prior to admission to the clinical research center.
• Medical history without significant findings per the PI
• Resting supine systolic BP of ≤140mmHg and diastolic BP of ≤90mmHg
• ECGs (via 12 lead) showing NCS findings per PI
• All clinical laboratory tests of blood and urine, WNL and/or without clinically significant findings
• Willing/able to sign ICF
• Normal bowel habits
• Negative medical history regarding fecal blood positivity
• Normal and/or NCS spot protein/creatinine (PCR) ratio.

Exclusion criteria

• Previous participation in the current study
• History of prior exposure to bevacizumab
• Evidence of clinically significant findings
• Cognitive and / or mentally impaired handicaps that would affect ability to make an informed consent and/or remain compliant to the requirements of this trial.
• History of relevant drug and/or food related allergies.
• History of or known hypersensitivity to bevacizumab or other recombinant human or humanized antibodies or inactive ingredients.
• Tobacco product use w/I 1 yr. prior to drug administration.
• History of ETOH and or drug abuse/addiction
• Positive urine drug and ETOH screen for opiates, methadone, cocaine, amphetamines including XTC, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and ETOH.
• Average intake of more than 24 units of ETOH / wk. (1 unit of ETOH equals ~250mL of beer, 100mL of wine or 35mL of spirits).
• Consumption of any foods containing poppy seeds w/I 48 hrs. prior to screening and admission to the clinical research center
• Positive screen for Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies.
• Participation in a drug study w/I 60days or 5 half-lives of the previous drug.
• Participation in more than 3 other drug studies in the 10months prior to drug administration in the current protocol.
• Donation or loss of more than 100mL of blood w/I 60days prior to drug administration. Donation or loss of more than 1.5liters of blood w/I the 10months prior to drug administration.
• Strenuous exercise w/I 96 hrs. Prior to admission to the clinical research center.
• Significant or acute illness w/I 5days prior to drug administration that may impact safety assessments per the judgement of the PI.
• Unsuitable veins for infusion and/or venepuncture
• Surgery including surgery with suturing via a dental procedure or would dehiscence w/I 28days of dosing. Any planned surgery or dental procedures during the study and for at least 30days after follow up.
• Presence of a non-healing wound or fracture.
• History of bleeding disorders
• History of thromboembolic conditions
• History of gastrointestinal perforations or any fistulae.
• History of orthostatic hypotension, fainting spells, blackouts for any reasons.
• History of hypertension
• Medically significant dental disease or dental neglect with signs and or symptoms of local or systemic infection that would likely require a dental procedure during the course of study.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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111 participants in 3 patient groups

MYL-1402O

Experimental group

Description:

MYL-1402O (bevacizumab), single 1mg/kg i.v. infusion over 90 minutes.

Treatment:

Drug: MYL-1402O

US Marketed Avastin (R)

Active Comparator group

Description:

US Marketed Avastin(R) (bevacizumab), single 1mg/kg i.v. infusion over 90 minutes.

Treatment:

Drug: US marketed Avastin(R)

EU Marketed Avastin(R)

Active Comparator group

Description:

EU Marketed Avastin(R) (bevacizumab), single 1mg/kg i.v. infusion over 90 minutes.

Treatment:

Drug: EU marketed Avastin(R)