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Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase

Primary Purpose

Healthy, Hypercholesterolemia

Status
Terminated
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Cohort 1: bococizumab 150 mg + rHuPH20
Cohort 2: bococizumab 300 mg
Cohort 3: bococizumab 300 mg + rHuPH20
Cohort 5: bococizumab 450 mg + rHuPH20
Cohort 4: bococizumab 300 mg + rHuPH20
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy focused on measuring pharmacokinetics, pharmacodynamics, RN316, recombinant human hyaluronidase

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years.
  • Healthy subjects must have fasting LDL-C >/= 70 to </= 190 mg/dL at two qualifying visits.
  • Hypercholesterolemic subjects must be on a stable daily dose of statin for at least 45 days before dosing and fasting LDL-C must be >/= 70 mg/dL.

Exclusion Criteria:

  • Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed.
  • Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors.
  • Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.

Sites / Locations

  • Pfizer Clinical Research Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Cohort 1: bococizumab 150 mg + rHuPH20

Cohort 2: bococizumab 300 mg

Cohort 3: bococizumab 300 mg + rHuPH20

Cohort 5: bococizumab 450 mg + rHUPH20

Cohort 4: bococizumab 300 mg + rHuPH20

Arm Description

bococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

bococizumab 300 mg administered subcutaneously to healthy volunteers

bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

bococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin

Outcomes

Primary Outcome Measures

AUCinf of bococizumab
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞), if data permits (otherwise AUClast will be used).
Cmax of bococizumab
Maximum Observed Plasma Concentration (Cmax)

Secondary Outcome Measures

Tmax
Time to Reach Maximum Observed Plasma Concentration (Tmax)
CL/F
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance is influenced by the fraction of the dose absorbed. Clearance is estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Vz/F
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after dose (Vz/F) is influenced by the fraction absorbed.
t1/2
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
LDL-C at Week 4
Absolute value, and absolute change and % change in LDL cholesterol at Week 4 following bococizumab administration alone and when co-mixed with rHuPH20.
MaxELDL-C
Maximum LDL-C lowering calculated using absolute LDL-C values
Tmax, LDL-C
Time to MaxELDL-C calculated using absolute LDL-C values
AUEC85
Area under the LDL-C concentration-time curve calculated using absolute LDL-C values
AEs
Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)
Laboratory tests
Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology
Vital signs
Incidence of abnormal and clinically relevant vital signs
AUClast of bococizumab
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
ADA
Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.
nAb
Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.

Full Information

First Posted
January 6, 2016
Last Updated
October 19, 2016
Sponsor
Pfizer
Collaborators
Halozyme Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02667223
Brief Title
Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase
Official Title
A Phase 1, Open Label, Randomized, Single Dose, Dose Escalation Study To Assess The Subcutaneous Pharmacokinetics And Pharmacodynamics Of Bococizumab (pf 04950615) Alone And In Co Mixture With Recombinant Human Hyaluronidase (rhuph20, Pf 06744547) In Healthy And Hypercholesterolemic Adult Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early on July 8, 2016 due to business priorities regarding study execution.
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Halozyme Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. After discharge, subjects will return to the research clinic 15 times during 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Hypercholesterolemia
Keywords
pharmacokinetics, pharmacodynamics, RN316, recombinant human hyaluronidase

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: bococizumab 150 mg + rHuPH20
Arm Type
Experimental
Arm Description
bococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Arm Title
Cohort 2: bococizumab 300 mg
Arm Type
Active Comparator
Arm Description
bococizumab 300 mg administered subcutaneously to healthy volunteers
Arm Title
Cohort 3: bococizumab 300 mg + rHuPH20
Arm Type
Experimental
Arm Description
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Arm Title
Cohort 5: bococizumab 450 mg + rHUPH20
Arm Type
Experimental
Arm Description
bococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Arm Title
Cohort 4: bococizumab 300 mg + rHuPH20
Arm Type
Experimental
Arm Description
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin
Intervention Type
Biological
Intervention Name(s)
Cohort 1: bococizumab 150 mg + rHuPH20
Intervention Description
bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers
Intervention Type
Biological
Intervention Name(s)
Cohort 2: bococizumab 300 mg
Intervention Description
bococizumab 300 mg administered SC to healthy volunteers
Intervention Type
Biological
Intervention Name(s)
Cohort 3: bococizumab 300 mg + rHuPH20
Intervention Description
bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers
Intervention Type
Biological
Intervention Name(s)
Cohort 5: bococizumab 450 mg + rHuPH20
Intervention Description
bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers
Intervention Type
Biological
Intervention Name(s)
Cohort 4: bococizumab 300 mg + rHuPH20
Intervention Description
bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin
Primary Outcome Measure Information:
Title
AUCinf of bococizumab
Description
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞), if data permits (otherwise AUClast will be used).
Time Frame
Day 1 - Day 85
Title
Cmax of bococizumab
Description
Maximum Observed Plasma Concentration (Cmax)
Time Frame
Day 1 - Day 85
Secondary Outcome Measure Information:
Title
Tmax
Description
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame
Day 1 - Day 85
Title
CL/F
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance is influenced by the fraction of the dose absorbed. Clearance is estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Day 1 - Day 85
Title
Vz/F
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after dose (Vz/F) is influenced by the fraction absorbed.
Time Frame
Day 1 - Day 85
Title
t1/2
Description
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame
Day 1 - Day 85
Title
LDL-C at Week 4
Description
Absolute value, and absolute change and % change in LDL cholesterol at Week 4 following bococizumab administration alone and when co-mixed with rHuPH20.
Time Frame
Baseline to Week 4
Title
MaxELDL-C
Description
Maximum LDL-C lowering calculated using absolute LDL-C values
Time Frame
Baseline up to Day 85
Title
Tmax, LDL-C
Description
Time to MaxELDL-C calculated using absolute LDL-C values
Time Frame
Baseline up to Day 85
Title
AUEC85
Description
Area under the LDL-C concentration-time curve calculated using absolute LDL-C values
Time Frame
Baseline up to Day 85
Title
AEs
Description
Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)
Time Frame
Baseline up to Day 85
Title
Laboratory tests
Description
Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology
Time Frame
Baseline up to Day 85
Title
Vital signs
Description
Incidence of abnormal and clinically relevant vital signs
Time Frame
Baseline up to Day 85
Title
AUClast of bococizumab
Description
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time Frame
Day 1 - Day 85
Title
ADA
Description
Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.
Time Frame
Day 1 - Day 85
Title
nAb
Description
Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.
Time Frame
Day 1- Day 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years. Healthy subjects must have fasting LDL-C >/= 70 to </= 190 mg/dL at two qualifying visits. Hypercholesterolemic subjects must be on a stable daily dose of statin for at least 45 days before dosing and fasting LDL-C must be >/= 70 mg/dL. Exclusion Criteria: Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed. Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors. Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Clinical Research Unit
City
Brussels
ZIP/Postal Code
B-1070
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
30623096
Citation
Bass A, Plotka A, Mridha K, Sattler C, Kim AM, Plowchalk DR. Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co-mixture with recombinant human hyaluronidase: A phase 1 randomized trial. Health Sci Rep. 2018 Jul 18;1(9):e61. doi: 10.1002/hsr2.61. eCollection 2018 Sep.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1481051&StudyName=A%20Phase%201%2C%20Open%20Label%2C%20Randomized%2C%20Single%20Dose%2C%20Dose%20Escalation%20Study%20To%20Assess%20The%20Subcutaneous%20Pharmacokinetics%20And%20Pharmacodynamics%20Of%20Bococizumab%20%28pf%2004950615%29%20Alone%20And%20In%20Co%20Mixture%20With%20Recombinant%20Human%20Hyaluronidase%20%28rhuph20%2C%20Pf%2006744547%29%20In%20Healthy%20And%20Hypercholesterolemic%20Adult%20Subjects
Description
To obtain contact information for a study center near you, click here.
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1481051&StudyName=A+Phase+1%2C+Open+Label%2C+Randomized%2C+Single+Dose%2C+Dose+Escalation+Study+To+Assess+The+Subcutaneous+Pharmacokinetics+And+Pharmacodynamics+Of+Bococizumab+%28pf+04950615%29+Alone+And+In+Co+Mixture+With+Recombinant+Human+Hyaluronidase+%28rhuph20%2C+Pf+06744547%29+In+Healthy+And+Hypercholesterolemic+Adult+Subjects
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase

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