Clinical trial NCT02458209: Single Dose Manufacturing Site (Pfizer vs. BIP) And Device (Prefilled Syringe vs. Prefilled Pen) Comparability Study For Bococizumab In Healthy Volunteers
Official title: A Phase 1, Open-label, Randomized, Single Dose, Parallel Group Comparability Study To Assess The Subcutaneous Pharmacokinetics And Pharmacodynamics Of Bococizumab In Healthy Adult Subjects For Comparisons Of Drug Substance Manufactured At Two Different Locations And Administration Via Prefilled Syringe Vs. Prefilled Pen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: PK, bococizumab, comparability, LDL-C
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-06-01
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: Day 1 - Day 85
measure: AUCinf
timeFrame: Day 1 - Day 85
measure: Cmax for bococizumab using DS from Pfizer as comapred to DS from BIP
timeFrame: Day 1 - Day 85
measure: AUCinf for bococizumab using DS from Pfizer as comapred to DS from BIP
timeFrame: Day 1 - Day 85
measure: Cmax for bococizumab using PFS as comapred to PFP
timeFrame: Day 1 - Day 85
measure: AUCinf for bococizumab using PFS as comapred to PFP
timeFrame: Day 1 - Day 85
Secondary outcomes:
measure: MaxELDL-C
timeFrame: Day 1 - Day 85
measure: AUEClast
timeFrame: Day 1 - Day 85
measure: Tmax,LDL-C
timeFrame: Day 1 - Day 85
measure: Tmax
timeFrame: Day 1 - Day 85
measure: CL/F
timeFrame: Day 1 - Day 85
measure: Vz/F
timeFrame: Day 1 - Day 85
measure: T1/2
timeFrame: Day 1 - Day 85
measure: AUClast
timeFrame: Day 1 - Day 85
measure: Incidence of ADAs and neutralizing antibodies
timeFrame: Day 1 - 85
measure: Titer for ADAs and neutralizing antibodies
timeFrame: Day 1 - 85
measure: Incidence, severity and causal relationship of treatment emergent AEs
timeFrame: Day 1 - 85
measure: Incidence and severity of ISRs
timeFrame: Day 1 - 85
measure: Incidence of abnormal and clinically relevant safety laboratory parameters
timeFrame: Day 1 - 85
measure: MaxELDL-C using DS from Pfizer as compared to BIP, if applicable
timeFrame: Day 1 - Day 85
measure: AUEClast using DS from Pfizer as compared to BIP, if applicable
timeFrame: Day 1 - Day 85
measure: MaxELDL-C using PFS as compared to PFP, if applicable
timeFrame: Day 1 - Day 85
measure: AUEClast using PFS as compared to PFP, if applicable
timeFrame: Day 1 - Day 85
Other outcomes:
measure: PCSK9
timeFrame: Day 1 - Day 85
measure: total cholesterole
timeFrame: Day 1 - Day 85
measure: HDL-C
timeFrame: Day 1 - Day 85
measure: Non HDL-C
timeFrame: Day 1 - Day 85
measure: triglyceride
timeFrame: Day 1 - Day 85
Locations:
city: Hollywood
country: United States
facility: Broward Research Group
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates, LLC
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research, LLC
state: Florida
city: Saint Paul
country: United States
facility: Prism Research, LLC
state: Minnesota
city: High Point
country: United States
facility: High Point Clinical Trials Center, LLC
state: North Carolina
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wang EQ, Plotka A, Salageanu J, Baltrukonis D, Mridha K, Frederich R, Sullivan BE. Comparative Pharmacokinetics and Pharmacodynamics of Bococizumab Following a Single Subcutaneous Injection Using Drug Substance Manufactured at Two Sites or Administration via Two Different Devices. Clin Pharmacol Drug Dev. 2019 Jan;8(1):40-48. doi: 10.1002/cpdd.454. Epub 2018 Apr 24.