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

Phase 1

Terminated

• Conditions: Hypercholesterolemia; Healthy

• Registration Number: NCT02667223
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-01-06
• Study First Submitted QC: 2016-01-25
• Study First Posted: 2016-01-28
• Study Start: 2016-02
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-19
• Last Update Posted: 2016-10-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cmax of bococizumab	Day 1 - Day 85	Maximum Observed Plasma Concentration (Cmax)
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).

Secondary Outcome Measures

Name	Time	Method
AUEC85	Baseline up to Day 85	Area under the LDL-C concentration-time curve calculated using absolute LDL-C values
Laboratory tests	Baseline up to Day 85	Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology
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.
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.
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.
Tmax, LDL-C	Baseline up to Day 85	Time to MaxELDL-C calculated using absolute LDL-C values
AEs	Baseline up to Day 85	Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)
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.
Tmax	Day 1 - Day 85	Time to Reach Maximum Observed Plasma Concentration (Tmax)
t1/2	Day 1 - Day 85	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
MaxELDL-C	Baseline up to Day 85	Maximum LDL-C lowering calculated using absolute LDL-C values
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.

Trial Locations

Locations (1)

Pfizer Clinical Research Unit; 🇧🇪 Brussels, Belgium