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

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Bococizumab (PF-04950615;RN316); Drug: Bococizumab (PF-04950615;RN316); Drug: Bococizumab (PF-04950615;RN316); Drug: Placebo; Drug: Ezetimibe; Drug: Bococizumab (PF-04950615;RN316); Drug: Bococizumab (PF-04950615;RN316); Drug: Bococizumab (PF-04950615;RN316); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Gunma
    • Maebashi, Gunma, Japan, 371-0022
      • Maebashi Hirosegawa Clinic
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0064
      • Yokohama Minoru Clinic
  • Osaka
    • Suita, Osaka, Japan, 565-0853
      • Heishinkai Medical Group Incorporated OCROM Clinic
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-0041
      • Meiwa Hospital
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Tokyo-Eki Center-building Clinic
    • Shinjuku-ku, Tokyo, Japan, 162-0053
      • Clinical Research Hospital Tokyo
    • Shinjuku-ku, Tokyo, Japan, 169-0072
      • Oda Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0022
      • Heishinkai Medical Group Incorporated ToCROM Clinic
    • Toshima-ku, Tokyo, Japan, 171-0014
      • Sekino Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Population A; 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.	Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 50 mg subcutaneous administration at every two weeks (Q14D SC) for 16 week; Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 100 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 150 mg Q14D SC for 16 week; Drug: Placebo; Atorvastatin plus PF-04950615 Placebo Q14D SC for 16 week; Drug: Ezetimibe; Atorvastatin plus Ezetimibe 10 mg oral administration once daily for 16 week (open); Drug: Bococizumab (PF-04950615;RN316); 50 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); 100 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); 150 mg Q14D SC for 16 week; Drug: Placebo; Placebo Q14D SC for 16 week
Experimental: Population B; 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.	Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 50 mg subcutaneous administration at every two weeks (Q14D SC) for 16 week; Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 100 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); Atorvastatin plus PF-04950615 150 mg Q14D SC for 16 week; Drug: Placebo; Atorvastatin plus PF-04950615 Placebo Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); 50 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); 100 mg Q14D SC for 16 week; Drug: Bococizumab (PF-04950615;RN316); 150 mg Q14D SC for 16 week; Drug: Placebo; Placebo Q14D SC for 16 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Day 85
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.	Baseline, Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
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.	Baseline, Day 85, 113
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.	Baseline, Day 85, 113
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.	Baseline up to Day 113
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.	Baseline up to Day 169
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.	Baseline up to Day 169
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.	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)
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.	Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
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.	Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
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.	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)
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.	Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
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.	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)
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.	Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
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.	Day 1, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Japan; PF-04950615
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe; Bococizumab
• Other Study ID Numbers: B1481036