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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: bococizumab PFS:Pfizer
* Biological: bococizumab PFS: BIP
* Biological: bococizumab PFP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 65 years Body Mass Index (BMI) 33.0 kg/m2 or lower; and a total body weight 60 to 90 kg (132 198 lbs) inclusive Fasting LDL-C must be 80 to 200 mg/dL at two qualifying visits: initial screening (Days -28 to -14) and Day -7. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: 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 Any condition possibly affecting drug absorption. 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 History of allergic or anaphylactic reaction to any therapeutic or diagnostic mAb or molecules made of components of mAb History of regular alcohol consumption : >7 drinks/wk (F) or 14 drinks/wk (M) History of sensitivity to heparin or heparin-induced thrombocytopenia. Positive urine drug screen. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. Screening seated BP of 140/90 mm Hg or higher Screening 12-lead ECG demonstrating QTc >450 or a QRS interval >120 msec Subjects with prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors. Treatment with marketed or investigational mAbs within 6 months or 5 half-lives of Day 1 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. Use of prescription or nonprescription drugs within 7 days or 5 half-lives of Day 1; 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. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, bococizumab, comparability, LDL-C