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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Biological: bococizumab PFP

• Registration Number: NCT02458209
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-01
• Study First Submitted QC: 2015-05-27
• Study First Posted: 2015-06-01
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-07
• Last Update Posted: 2016-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 470

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment C	bococizumab PFP	150 mg SC dose administered in a prefilled pen using drug substance manufactured at Pfizer Andover.

Primary Outcome Measures

Name	Time	Method
Cmax	Day 1 - Day 85	maximal plasma concentration
AUCinf	Day 1 - Day 85	area under the concentration time curve from time 0 extrapolated to infinite time (AUCinf)
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 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 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 PFS as comapred to PFP	Day 1 - Day 85	AUcinf of bococizumab administered via prefilled syringe vs. a prefilled pen

Secondary Outcome Measures

Name	Time	Method
CL/F	Day 1 - Day 85	apparent clearance
Incidence of ADAs and neutralizing antibodies	Day 1 - 85	Incidence of anti-drug antibodies and neutralizing antibodies (if applicable).
Titer for ADAs and neutralizing antibodies	Day 1 - 85	Titer for anti-drug antibodies and neutralizing antibodies (if applicable).
Incidence and severity of ISRs	Day 1 - 85	Incidence, and severity of injection site reactions
Tmax	Day 1 - Day 85	Time to Cmax
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)
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
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
Tmax,LDL-C	Day 1 - Day 85	Time for MaxELDL- C
Vz/F	Day 1 - Day 85	Apparent volume of distribution
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 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
Incidence, severity and causal relationship of treatment emergent AEs	Day 1 - 85	Incidence, severity and causal relationship of treatment emergent AEs (TEAEs)
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.

Trial Locations

Locations (5)

Broward Research Group; 🇺🇸 Hollywood, Florida, United States

Miami Research Associates, LLC; 🇺🇸 South Miami, Florida, United States

MRA Clinical Research, LLC; 🇺🇸 South Miami, Florida, United States

Prism Research, LLC; 🇺🇸 Saint Paul, Minnesota, United States

High Point Clinical Trials Center, LLC; 🇺🇸 High Point, North Carolina, United States