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

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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02667223

Enrollment

Registered

2016-01-28

Start date

2016-02-29

Completion date

2016-07-31

Last updated

2016-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy, Hypercholesterolemia

Keywords

pharmacokinetics, pharmacodynamics, RN316, recombinant human hyaluronidase

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.

Interventions

BIOLOGICALCohort 1: bococizumab 150 mg + rHuPH20

bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers

BIOLOGICALCohort 2: bococizumab 300 mg

bococizumab 300 mg administered SC to healthy volunteers

BIOLOGICALCohort 3: bococizumab 300 mg + rHuPH20

bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers

BIOLOGICALCohort 5: bococizumab 450 mg + rHuPH20

bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers

BIOLOGICALCohort 4: bococizumab 300 mg + rHuPH20

bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin

Study design

Allocation

RANDOMIZED

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
AUCinf of bococizumab	Day 1 - Day 85	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	Day 1 - Day 85	Maximum Observed Plasma Concentration (Cmax)

Secondary

Measure	Time frame	Description
Vz/F	Day 1 - Day 85	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	Day 1 - Day 85	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
LDL-C at Week 4	Baseline to 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	Baseline up to Day 85	Maximum LDL-C lowering calculated using absolute LDL-C values
Tmax, LDL-C	Baseline up to Day 85	Time to MaxELDL-C calculated using absolute LDL-C values
AUEC85	Baseline up to Day 85	Area under the LDL-C concentration-time curve calculated using absolute LDL-C values
Tmax	Day 1 - Day 85	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Laboratory tests	Baseline up to Day 85	Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology
Vital signs	Baseline up to Day 85	Incidence of abnormal and clinically relevant vital signs
AUClast of bococizumab	Day 1 - Day 85	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
ADA	Day 1 - Day 85	Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.
nAb	Day 1- Day 85	Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.
AEs	Baseline up to Day 85	Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)
CL/F	Day 1 - Day 85	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.

Countries

Belgium

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 23, 2026