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

• ClinicalTrials.gov Identifier: NCT02055976
• Recruitment Status: Completed
• First Posted: February 5, 2014
• Results First Posted: February 8, 2019
• Last Update Posted: February 8, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 22, 2014
• First Posted Date: February 5, 2014
• Results First Submitted Date: September 22, 2017
• Results First Posted Date: February 8, 2019
• Last Update Posted Date: February 8, 2019
• Actual Study Start Date: March 2014
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2018)

• Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 [ Time Frame: Baseline, 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 [ Time Frame: Baseline, 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.

• Original Primary Outcome Measures (submitted: February 4, 2014): Percent Change from Baseline in LDL-C at Week 12 and 16 [ Time Frame: Week 12 and 16 ]

Current Secondary Outcome Measures (submitted: September 4, 2018)

• Low Density Lipoprotein-Cholesterol (LDL-C) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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]) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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) [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169 ]
  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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline, Day 85, 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 [ Time Frame: Baseline up to 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.
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 169 ]
  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 [ Time Frame: Baseline up to Day 169 ]
  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 [ 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) ]
  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 [ Time Frame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose) ]
  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 [ Time Frame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose) ]
  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 [ 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) ]
  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 [ Time Frame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose) ]
  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 [ 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) ]
  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 [ Time Frame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose) ]
  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) [ Time Frame: Day 1, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141 ]
  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.

Original Secondary Outcome Measures (submitted: February 4, 2014)

• Actual Value and Change from Baseline in LDL-C [ Time Frame: Baseline, Week 12 and 16 ]
• Actual Value, Change from Baseline and Percent Change from Baseline in Lipid parameters [ Time Frame: Baseline, Week 12 and 16 ]
  Total Cholesterol (TC), ApoB, ApoA-I, ApoA-II, Lp(a), High Density Lipoprotein Cholesterol, VLDL-C, Triglyceride, Non-HDL-cholesterol, TC/HDL-C ratio and ApoB/ApoA-I ratio.
• Proportion of subjects having LDL-C less than particular limits (<100 mg/dL, <70 mg/dL, <40 mg/dL, <25 mg/dL, <10 mg/dL) [ Time Frame: Week 12 and 16 ]
• Anti-drug antibody (ADA) [ Time Frame: Week 24 ]
• Area Under the Curve (AUC) [ Time Frame: Week 20 ]
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Week 20 ]
• Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Week 20 ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Week 20 ]
• Plasma Decay Half-Life (t1/2) [ Time Frame: Week 20 ]
• Plasma concentration of PCSK9 [ Time Frame: Week 20 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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.
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypercholesterolemia

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Placebo
  • Drug: Ezetimibe
• 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.
  Interventions:

  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Bococizumab (PF-04950615;RN316)
  • Drug: Placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 9, 2015): 218
• Original Estimated Enrollment (submitted: February 4, 2014): 216
• Actual Study Completion Date: January 2015
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02055976
• Other Study ID Numbers: B1481036
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: September 2018