Single Dose Manufacturing Site (Pfizer vs. BIP) And Device (Prefilled Syringe vs. Prefilled Pen) Comparability Study For Bococizumab In Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: bococizumab PFS:Pfizer; Biological: bococizumab PFS: BIP; Biological: bococizumab PFP

• Study Type: Interventional
• Enrollment (Actual): 470
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hollywood, Florida, United States, 33024
      • Broward Research Group
    • South Miami, Florida, United States, 33143
      • Miami Research Associates, LLC
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research, LLC
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism research, LLC
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; 150 mg SC dose administered in a prefilled syringe using drug substance manufactured at Pfizer Andover	Biological: bococizumab PFS:Pfizer; 150 mg bococizumab administered SC in a prefilled syringe using drug substance manufactured at Pfizer Andover
Experimental: Treatment B; • Treatment B: 150 mg SC dose administered in a prefilled syringe using drug substance manufactured at Boehringer Ingelheim Pharma	Biological: bococizumab PFS: BIP; 150 mg bococizumab administered SC in a prefilled syringe using drug substance manufactured at Boehringer Ingelheim Pharma.
Experimental: Treatment C; 150 mg SC dose administered in a prefilled pen using drug substance manufactured at Pfizer Andover.	Biological: bococizumab PFP; 150 mg bococizumab administered SC in a prefilled pen using drug substance manufactured at Pfizer Andover

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximal plasma concentration	Day 1 - Day 85
AUCinf	area under the concentration time curve from time 0 extrapolated to infinite time (AUCinf)	Day 1 - Day 85
Cmax for bococizumab using DS from Pfizer as comapred to DS from BIP	Cmax of bococizumab using drug substance (DS) manufactured by Pfizer vs. DS manufactured by BIP	Day 1 - Day 85
AUCinf for bococizumab using DS from Pfizer as comapred to DS from BIP	Cmax of bococizumab using drug substance (DS) manufactured by Pfizer vs. DS manufactured by BIP	Day 1 - Day 85
Cmax for bococizumab using PFS as comapred to PFP	Cmax of bococizumab administered via prefilled syringe vs. a prefilled pen	Day 1 - Day 85
AUCinf for bococizumab using PFS as comapred to PFP	AUcinf of bococizumab administered via prefilled syringe vs. a prefilled pen	Day 1 - Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MaxELDL-C	Maximum lowering in LDL C	Day 1 - Day 85
AUEClast	Area under the LDL C concentration time profile from time zero to the time of the last quantifiable concentration (Clast)	Day 1 - Day 85
Tmax,LDL-C	Time for MaxELDL- C	Day 1 - Day 85
Tmax	Time to Cmax	Day 1 - Day 85
CL/F	apparent clearance	Day 1 - Day 85
Vz/F	Apparent volume of distribution	Day 1 - Day 85
T1/2	terminal half-life	Day 1 - Day 85
AUClast	Area under the concentration time curve from time 0 to the time of last quantifiable concentration	Day 1 - Day 85
Incidence of ADAs and neutralizing antibodies	Incidence of anti-drug antibodies and neutralizing antibodies (if applicable).	Day 1 - 85
Titer for ADAs and neutralizing antibodies	Titer for anti-drug antibodies and neutralizing antibodies (if applicable).	Day 1 - 85
Incidence, severity and causal relationship of treatment emergent AEs	Incidence, severity and causal relationship of treatment emergent AEs (TEAEs)	Day 1 - 85
Incidence and severity of ISRs	Incidence, and severity of injection site reactions	Day 1 - 85
Incidence of abnormal and clinically relevant safety laboratory parameters	Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry, hematology, and vital signs.	Day 1 - 85
MaxELDL-C using DS from Pfizer as compared to BIP, if applicable	Maximum lowering in LDL-C using DS manufactured by Pfizer vs. BIP, if applicable	Day 1 - Day 85
AUEClast using DS from Pfizer as compared to BIP, if applicable	Area under the LDL-C curve using DS manufactured by Pfizer vs. BIP, if applicable	Day 1 - Day 85
MaxELDL-C using PFS as compared to PFP, if applicable	Maximum lowering in LDL-C using prefilled syringe vs. prefilled pen , if applicable	Day 1 - Day 85
AUEClast using PFS as compared to PFP, if applicable	Area under the LDL-C curve using prefilled syringe vs. prefilled pen , if applicable	Day 1 - Day 85

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCSK9	on trial ng/mL PCSK9 concentration, ng/mL change from baseline and percent change from baseline in PCSK9 following bococizumab administration	Day 1 - Day 85
total cholesterole	on trial mg/mL total cholesterol concentration, change from baseline and percent change from baseline in total cholesterol following bococizumab administration	Day 1 - Day 85
HDL-C	on trial mg/mL HDL-C concentration, change from baseline and percent change from baseline in HDL-C following bococizumab administration	Day 1 - Day 85
Non HDL-C	on trial mg/mL non HDL-C concentration, change from baseline and percent change from baseline in non HDL-C following bococizumab administration	Day 1 - Day 85
triglyceride	on trial mg/mL triglyceride concentration, change from baseline and percent change from baseline in triglyceride following bococizumab administration	Day 1 - Day 85

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 1, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Estimate): March 8, 2016
• Last Update Submitted That Met QC Criteria: March 7, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: PK, bococizumab, comparability, LDL-C
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bococizumab
• Other Study ID Numbers: B1481026