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

October 19, 2016 updated by: Pfizer

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, B-1070
        • Pfizer Clinical Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: bococizumab 150 mg + rHuPH20
bococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Biological: Cohort 1: bococizumab 150 mg + rHuPH20
bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers
Active Comparator: Cohort 2: bococizumab 300 mg
bococizumab 300 mg administered subcutaneously to healthy volunteers
Biological: Cohort 2: bococizumab 300 mg
bococizumab 300 mg administered SC to healthy volunteers
Experimental: Cohort 3: bococizumab 300 mg + rHuPH20
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Biological: Cohort 3: bococizumab 300 mg + rHuPH20
bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers
Experimental: Cohort 5: bococizumab 450 mg + rHUPH20
bococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Biological: Cohort 5: bococizumab 450 mg + rHuPH20
bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers
Experimental: Cohort 4: bococizumab 300 mg + rHuPH20
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin
Biological: Cohort 4: bococizumab 300 mg + rHuPH20
bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
AUCinf of bococizumab
Time Frame: 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).
Day 1 - Day 85
Cmax of bococizumab
Time Frame: Day 1 - Day 85
Maximum Observed Plasma Concentration (Cmax)
Day 1 - Day 85

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tmax
Time Frame: Day 1 - Day 85
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 1 - Day 85
CL/F
Time Frame: 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.
Day 1 - Day 85
Vz/F
Time Frame: 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.
Day 1 - Day 85
t1/2
Time Frame: Day 1 - Day 85
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Day 1 - Day 85
LDL-C at Week 4
Time Frame: 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.
Baseline to Week 4
MaxELDL-C
Time Frame: Baseline up to Day 85
Maximum LDL-C lowering calculated using absolute LDL-C values
Baseline up to Day 85
Tmax, LDL-C
Time Frame: Baseline up to Day 85
Time to MaxELDL-C calculated using absolute LDL-C values
Baseline up to Day 85
AUEC85
Time Frame: Baseline up to Day 85
Area under the LDL-C concentration-time curve calculated using absolute LDL-C values
Baseline up to Day 85
AEs
Time Frame: Baseline up to Day 85
Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)
Baseline up to Day 85
Laboratory tests
Time Frame: Baseline up to Day 85
Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology
Baseline up to Day 85
Vital signs
Time Frame: Baseline up to Day 85
Incidence of abnormal and clinically relevant vital signs
Baseline up to Day 85
AUClast of bococizumab
Time Frame: Day 1 - Day 85
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Day 1 - Day 85
ADA
Time Frame: Day 1 - Day 85
Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.
Day 1 - Day 85
nAb
Time Frame: Day 1- Day 85
Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.
Day 1- Day 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Halozyme Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 6, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 25, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 21, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B1481051
  • 2015-003568-36 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings