Healthy
Conditions
Keywords
PK, bococizumab, comparability, LDL-C
Brief summary
This is an open label, single dose, randomized, parallel group study in healthy adult subjects to assess the comparability of bococizumab administered in a prefilled syringe vs. prefilled pen and comparability between drug substance manufactured at Pfizer Andover vs. Boehringer Ingelheim Pharma.
Interventions
BIOLOGICALbococizumab PFS:Pfizer
150 mg bococizumab administered SC in a prefilled syringe using drug substance manufactured at Pfizer Andover
BIOLOGICALbococizumab PFS: BIP
150 mg bococizumab administered SC in a prefilled syringe using drug substance manufactured at Boehringer Ingelheim Pharma.
BIOLOGICALbococizumab PFP
150 mg bococizumab administered SC in a prefilled pen using drug substance manufactured at Pfizer Andover
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and/or female subjects between the ages of 18 and 65 years 2. Body Mass Index (BMI) 33.0 kg/m2 or lower; and a total body weight 60 to 90 kg (132 198 lbs) inclusive 3. Fasting LDL-C must be 80 to 200 mg/dL at two qualifying visits: initial screening (Days -28 to -14) and Day -7. 4. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
1. Evidence or history of clinically significant disease or other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results 2. Any condition possibly affecting drug absorption. 3. Pregnant/breast feeding female subjects; male subjects with partners currently pregnant; male & female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception 4. History of allergic or anaphylactic reaction to any therapeutic or diagnostic mAb or molecules made of components of mAb 5. History of regular alcohol consumption : \>7 drinks/wk (F) or 14 drinks/wk (M) 6. History of sensitivity to heparin or heparin-induced thrombocytopenia. 7. Positive urine drug screen. 8. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. 9. Screening seated BP of 140/90 mm Hg or higher 10. Screening 12-lead ECG demonstrating QTc \>450 or a QRS interval \>120 msec 11. Subjects with prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors. 12. Treatment with marketed or investigational mAbs within 6 months or 5 half-lives of Day 1 13. Treatment with an investigational drug within 30 days or 5 half-lives of Day 1, and/or anticipated to take part in a clinical study during the duration of this study. 14. Use of prescription or nonprescription drugs within 7 days or 5 half-lives of Day 1; 15. Abnormal labs: AST/SGOT or ALT/SGPT greater than or equal to 1.2 × ULN; total bilirubin greater than or equal to 1.5 × ULN; CK \>1.5 × ULN or absolute value \>600 U/L. 16. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol. 17. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax for bococizumab using DS from Pfizer as comapred to DS from BIP | Day 1 - Day 85 | Cmax of bococizumab using drug substance (DS) manufactured by Pfizer vs. DS manufactured by BIP |
| AUCinf for bococizumab using PFS as comapred to PFP | Day 1 - Day 85 | AUcinf of bococizumab administered via prefilled syringe vs. a prefilled pen |
| AUCinf | Day 1 - Day 85 | area under the concentration time curve from time 0 extrapolated to infinite time (AUCinf) |
| Cmax for bococizumab using PFS as comapred to PFP | Day 1 - Day 85 | Cmax of bococizumab administered via prefilled syringe vs. a prefilled pen |
| AUCinf for bococizumab using DS from Pfizer as comapred to DS from BIP | Day 1 - Day 85 | Cmax of bococizumab using drug substance (DS) manufactured by Pfizer vs. DS manufactured by BIP |
| Cmax | Day 1 - Day 85 | maximal plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vz/F | Day 1 - Day 85 | Apparent volume of distribution |
| T1/2 | Day 1 - Day 85 | terminal half-life |
| AUClast | Day 1 - Day 85 | Area under the concentration time curve from time 0 to the time of last quantifiable concentration |
| Incidence of ADAs and neutralizing antibodies | Day 1 - 85 | Incidence of anti-drug antibodies and neutralizing antibodies (if applicable). |
| Incidence, severity and causal relationship of treatment emergent AEs | Day 1 - 85 | Incidence, severity and causal relationship of treatment emergent AEs (TEAEs) |
| Incidence and severity of ISRs | Day 1 - 85 | Incidence, and severity of injection site reactions |
| Incidence of abnormal and clinically relevant safety laboratory parameters | Day 1 - 85 | Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry, hematology, and vital signs. |
| MaxELDL-C using DS from Pfizer as compared to BIP, if applicable | Day 1 - Day 85 | Maximum lowering in LDL-C using DS manufactured by Pfizer vs. BIP, if applicable |
| AUEClast using DS from Pfizer as compared to BIP, if applicable | Day 1 - Day 85 | Area under the LDL-C curve using DS manufactured by Pfizer vs. BIP, if applicable |
| MaxELDL-C using PFS as compared to PFP, if applicable | Day 1 - Day 85 | Maximum lowering in LDL-C using prefilled syringe vs. prefilled pen , if applicable |
| AUEClast using PFS as compared to PFP, if applicable | Day 1 - Day 85 | Area under the LDL-C curve using prefilled syringe vs. prefilled pen , if applicable |
| Titer for ADAs and neutralizing antibodies | Day 1 - 85 | Titer for anti-drug antibodies and neutralizing antibodies (if applicable). |
| MaxELDL-C | Day 1 - Day 85 | Maximum lowering in LDL C |
| AUEClast | Day 1 - Day 85 | Area under the LDL C concentration time profile from time zero to the time of the last quantifiable concentration (Clast) |
| Tmax,LDL-C | Day 1 - Day 85 | Time for MaxELDL- C |
| Tmax | Day 1 - Day 85 | Time to Cmax |
| CL/F | Day 1 - Day 85 | apparent clearance |
Other
| Measure | Time frame | Description |
|---|---|---|
| PCSK9 | Day 1 - Day 85 | on trial ng/mL PCSK9 concentration, ng/mL change from baseline and percent change from baseline in PCSK9 following bococizumab administration |
| triglyceride | Day 1 - Day 85 | on trial mg/mL triglyceride concentration, change from baseline and percent change from baseline in triglyceride following bococizumab administration |
| Non HDL-C | Day 1 - Day 85 | on trial mg/mL non HDL-C concentration, change from baseline and percent change from baseline in non HDL-C following bococizumab administration |
| HDL-C | Day 1 - Day 85 | on trial mg/mL HDL-C concentration, change from baseline and percent change from baseline in HDL-C following bococizumab administration |
| total cholesterole | Day 1 - Day 85 | on trial mg/mL total cholesterol concentration, change from baseline and percent change from baseline in total cholesterol following bococizumab administration |
Countries
United States
Outcome results
None listed