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Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects

Primary Purpose

Hypercholesterolemia

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Bococizumab (PF-04950615;RN316)
Bococizumab (PF-04950615;RN316)
Bococizumab (PF-04950615;RN316)
Placebo
Ezetimibe
Bococizumab (PF-04950615;RN316)
Bococizumab (PF-04950615;RN316)
Bococizumab (PF-04950615;RN316)
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring PF-04950615, Japan

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects whose LDL-C is not controlled by a stable dose of atorvastatin (Population A).
  • Subjects who are naïve to a treatment by lipid lowering drug and whose LDL-C is not controlled (Population B).

Exclusion Criteria:

  • Severe acute or chronic medical or psychiatric condition or laboratory abnormality.
  • Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception.
  • Subjects who were administered or prior exposed to PF-04950615 and/or anti-body targeting PCSK9.

Sites / Locations

  • Maebashi Hirosegawa Clinic
  • Yokohama Minoru Clinic
  • Heishinkai Medical Group Incorporated OCROM Clinic
  • Meiwa Hospital
  • Tokyo-Eki Center-building Clinic
  • Heishinkai Medical Group Incorporated ToCROM Clinic
  • Clinical Research Hospital Tokyo
  • Oda Clinic
  • Sekino Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Population A

Population B

Arm Description

A total of 9 groups in two population. Population A comprises hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin. A subject who is receiving a stable dose of atorvastatin will be randomized into one out of 5 dose groups.

A total of 9 groups in two population. Population B comprises hypercholesterolemic Japanese subjects who are naïve for a treatment by lipid lowering drug and whose fasting LDL-cholesterol is not controlled. A subject who is treatment naïve will be randomized into one out of 4 dose groups.

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 113
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.

Secondary Outcome Measures

Low Density Lipoprotein-Cholesterol (LDL-C)
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Total Cholesterol (TC)
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Percent Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Apolipoprotein B (ApoB)
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Apolipoprotein A-I (ApoA-I)
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Apolipoprotein A-II (ApoA-II)
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Lipoprotein (a) (Lp[a])
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
High Density Lipoprotein- Cholesterol (HDL-C)
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Very Low Density Lipoprotein-Cholesterol (VLDL-C)
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Triglyceride (TG)
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Non-High Density Lipoprotein- Cholesterol (Non-HDL-C)
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Percent Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 10, 25, 40, 70 and 100 Milligram Per Deciliter
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events between first dose of study drug and up to Day 169 that were absent before treatment or that worsened relative to pretreatment state. Adverse events included treatment emergent injection site adverse events and any clinically significant abnormal laboratory value.
Number of Participants With Anti-Drug Antibody (ADA) Response
Participants tested positive for ADA response on at least one post-baseline visit were reported. Participants with ADA titer level >=6.23 for PF-04950615 were considered ADA positive.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau). This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-04950615
Area under the plasma concentration-time profile from time zero extrapolated to infinite time. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Maximum Observed Plasma Concentration (Cmax) of PF-04950615
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Minimum Observed Plasma Trough Concentration (Cmin) of PF-04950615
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Terminal Elimination Half-Life (t1/2) of PF-04950615
Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Plasma Concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =6.99 nanogram per milliliter [ng/mL]) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Full Information

First Posted
January 22, 2014
Last Updated
September 4, 2018
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02055976
Brief Title
Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects
Official Title
A Phase 2 Double Blind, Parallel Group, Placebo Controlled, Randomized, Dose Ranging Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Twice Monthly Subcutaneous Doses In Hypercholesterolemic Japanese Subjects Who Are Receiving A Stable Dose Of Atorvastatin Or Treatment Naïve.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 2014 (Actual)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the low density lipoprotein cholesterol (LDL-C) lowering effect of Bococizumab (PF-04950615;RN316) administered subcutaneously at every two weeks (Q14D) in hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin, or who are naïve to a treatment by lipid lowering drug and whose LDL-C is not controlled.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
Keywords
PF-04950615, Japan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
218 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Population A
Arm Type
Experimental
Arm Description
A total of 9 groups in two population. Population A comprises hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin. A subject who is receiving a stable dose of atorvastatin will be randomized into one out of 5 dose groups.
Arm Title
Population B
Arm Type
Experimental
Arm Description
A total of 9 groups in two population. Population B comprises hypercholesterolemic Japanese subjects who are naïve for a treatment by lipid lowering drug and whose fasting LDL-cholesterol is not controlled. A subject who is treatment naïve will be randomized into one out of 4 dose groups.
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
Atorvastatin plus PF-04950615 50 mg subcutaneous administration at every two weeks (Q14D SC) for 16 week
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
Atorvastatin plus PF-04950615 100 mg Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
Atorvastatin plus PF-04950615 150 mg Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Atorvastatin plus PF-04950615 Placebo Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Ezetimibe
Intervention Description
Atorvastatin plus Ezetimibe 10 mg oral administration once daily for 16 week (open)
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
50 mg Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
100 mg Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Bococizumab (PF-04950615;RN316)
Intervention Description
150 mg Q14D SC for 16 week
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Q14D SC for 16 week
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85
Description
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85
Title
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 113
Description
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 113
Secondary Outcome Measure Information:
Title
Low Density Lipoprotein-Cholesterol (LDL-C)
Description
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113
Description
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Total Cholesterol (TC)
Description
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
Description
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
Description
Total cholesterol is the sum of all the cholesterol within the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Apolipoprotein B (ApoB)
Description
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
Description
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
Description
ApoB is a major protein that makes up LDL cholesterol and is involved in transporting cholesterol and triglycerides to cells and tissues in the body. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Apolipoprotein A-I (ApoA-I)
Description
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
Description
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
Description
ApoA1 is a major protein that is a component of HDL cholesterol and helps in clearing cholesterol from the blood by removing cholesterol from organs and tissues to be destroyed by the liver. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Apolipoprotein A-II (ApoA-II)
Description
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
Description
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
Description
ApoA-II is the second most abundant component of the HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Lipoprotein (a) (Lp[a])
Description
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
Description
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
Description
Lp(a) is a lipoprotein subclass which consists of an LDL-like particle and the specific apolipoprotein(a). Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
High Density Lipoprotein- Cholesterol (HDL-C)
Description
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
Description
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
Description
HDL-C is cholesterol in the bloodstream that is carried by high density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Very Low Density Lipoprotein-Cholesterol (VLDL-C)
Description
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
Description
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
Description
VLDL is a type of lipoprotein made by the liver and one of the five major groups of lipoproteins, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Triglyceride (TG)
Description
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
Description
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
Description
Triglycerides are a type of fat circulating in the blood and account for the majority of the fats circulating in the blood. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Non-High Density Lipoprotein- Cholesterol (Non-HDL-C)
Description
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
Description
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
Description
Non-HDL-C calculated as total cholesterol minus HDL cholesterol. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value.
Time Frame
Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
Title
Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Change from baseline = observed value minus baseline value.
Time Frame
Baseline, Day 85, 113
Title
Percent Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
Description
Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = ([observed value divided by baseline value] minus 1) multiplied by 100.
Time Frame
Baseline, Day 85, 113
Title
Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 10, 25, 40, 70 and 100 Milligram Per Deciliter
Description
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection.
Time Frame
Baseline up to Day 113
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
Description
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events between first dose of study drug and up to Day 169 that were absent before treatment or that worsened relative to pretreatment state. Adverse events included treatment emergent injection site adverse events and any clinically significant abnormal laboratory value.
Time Frame
Baseline up to Day 169
Title
Number of Participants With Anti-Drug Antibody (ADA) Response
Description
Participants tested positive for ADA response on at least one post-baseline visit were reported. Participants with ADA titer level >=6.23 for PF-04950615 were considered ADA positive.
Time Frame
Baseline up to Day 169
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615
Description
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau). This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hour (hr) post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-04950615
Description
Area under the plasma concentration-time profile from time zero extrapolated to infinite time. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615
Description
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Maximum Observed Plasma Concentration (Cmax) of PF-04950615
Description
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hr post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Minimum Observed Plasma Trough Concentration (Cmin) of PF-04950615
Description
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
Description
This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hour (hr) post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Terminal Elimination Half-Life (t1/2) of PF-04950615
Description
Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half. This outcome measure was to be analyzed in participants who received at least 1 dose of the PF-04950615.
Time Frame
Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
Title
Plasma Concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
Description
Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ =6.99 nanogram per milliliter [ng/mL]) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.
Time Frame
Day 1, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects whose LDL-C is not controlled by a stable dose of atorvastatin (Population A). Subjects who are naïve to a treatment by lipid lowering drug and whose LDL-C is not controlled (Population B). Exclusion Criteria: Severe acute or chronic medical or psychiatric condition or laboratory abnormality. Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception. Subjects who were administered or prior exposed to PF-04950615 and/or anti-body targeting PCSK9.
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
Maebashi Hirosegawa Clinic
City
Maebashi
State/Province
Gunma
ZIP/Postal Code
371-0022
Country
Japan
Facility Name
Yokohama Minoru Clinic
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
232-0064
Country
Japan
Facility Name
Heishinkai Medical Group Incorporated OCROM Clinic
City
Suita
State/Province
Osaka
ZIP/Postal Code
565-0853
Country
Japan
Facility Name
Meiwa Hospital
City
Chiyoda-ku
State/Province
Tokyo
ZIP/Postal Code
101-0041
Country
Japan
Facility Name
Tokyo-Eki Center-building Clinic
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
103-0027
Country
Japan
Facility Name
Heishinkai Medical Group Incorporated ToCROM Clinic
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0022
Country
Japan
Facility Name
Clinical Research Hospital Tokyo
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
162-0053
Country
Japan
Facility Name
Oda Clinic
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
169-0072
Country
Japan
Facility Name
Sekino Hospital
City
Toshima-ku
State/Province
Tokyo
ZIP/Postal Code
171-0014
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
31549625
Citation
Yokote K, Suzuki A, Li Y, Matsuoka N, Teramoto T. Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects . Int J Clin Pharmacol Ther. 2019 Dec;57(12):575-589. doi: 10.5414/CP203418.
Results Reference
derived
PubMed Identifier
28539539
Citation
Yokote K, Kanada S, Matsuoka O, Sekino H, Imai K, Tabira J, Matsuoka N, Chaudhuri S, Teramoto T. Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naive - Results From a Randomized, Placebo-Controlled, Dose-Ranging Study. Circ J. 2017 Sep 25;81(10):1496-1505. doi: 10.1253/circj.CJ-16-1310. Epub 2017 May 23.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1481036&StudyName=Dose%20Ranging%20Study%20Of%20PF-04950615%20In%20Hypercholesterolemic%20Japanese%20Subjects
Description
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Learn more about this trial

Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects

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