Clinical trial NCT02055976: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: PF-04950615
Japan
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-02-05
Enrollment: 218
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85
timeFrame: Baseline, Day 85
measure: Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 113
timeFrame: Baseline, Day 113
Secondary outcomes:
measure: Low Density Lipoprotein-Cholesterol (LDL-C)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Total Cholesterol (TC)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Apolipoprotein B (ApoB)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Apolipoprotein A-I (ApoA-I)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Apolipoprotein A-II (ApoA-II)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Lipoprotein (a) (Lp[a])
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: High Density Lipoprotein- Cholesterol (HDL-C)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Very Low Density Lipoprotein-Cholesterol (VLDL-C)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Triglyceride (TG)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Triglyceride (TG) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Non-High Density Lipoprotein- Cholesterol (Non-HDL-C)
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio
timeFrame: Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169
measure: Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percent Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113
timeFrame: Baseline, Day 85, 113
measure: Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 10, 25, 40, 70 and 100 Milligram Per Deciliter
timeFrame: Baseline up to Day 113
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 169
measure: Number of Participants With Anti-Drug Antibody (ADA) Response
timeFrame: Baseline up to Day 169
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615
timeFrame: 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)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-04950615
timeFrame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615
timeFrame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
measure: Maximum Observed Plasma Concentration (Cmax) of PF-04950615
timeFrame: 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)
measure: Minimum Observed Plasma Trough Concentration (Cmin) of PF-04950615
timeFrame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
timeFrame: 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)
measure: Terminal Elimination Half-Life (t1/2) of PF-04950615
timeFrame: Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose)
measure: Plasma Concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
timeFrame: Day 1, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141
Other outcomes:
Locations:
city: Maebashi
country: Japan
facility: Maebashi Hirosegawa Clinic
state: Gunma
city: Yokohama
country: Japan
facility: Yokohama Minoru Clinic
state: Kanagawa
city: Suita
country: Japan
facility: Heishinkai Medical Group Incorporated OCROM Clinic
state: Osaka
city: Chiyoda-ku
country: Japan
facility: Meiwa Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Heishinkai Medical Group Incorporated ToCROM Clinic
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Oda Clinic
state: Tokyo
city: Toshima-ku
country: Japan
facility: Sekino Hospital
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.
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.