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SPIRE-LL: Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects With Primary Hyperlipidemia or Mixed Dyslipidemia At Risk Of Cardiovascular Events

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02100514
Collaborator
(none)
746
Enrollment
223
Locations
2
Arms
32.4
Actual Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a multicenter, double-blind, randomized study to access the efficacy, safety and tolerability of Bococizumab (PF-04950615; RN316) in subjects with hyperlipidemia receiving background statin therapy.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bococizumab (PF-04950615; RN316)
  • Other: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
746 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 52 Week Phase 3 Double-blind, Randomized, Placebo-controlled, Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events
Actual Study Start Date :
Oct 28, 2014
Actual Primary Completion Date :
Jul 15, 2016
Actual Study Completion Date :
Jul 10, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Bococizumab (PF-04950615; RN316)

Bococizumab (PF-04950615; RN316)

Drug: Bococizumab (PF-04950615; RN316)
150 mg every 2 weeks, subcutaneous injection for 52 weeks.
Placebo Comparator: placebo

Other: Placebo
Subcutaneous injection every 2 weeks for 52 weeks.

Outcome Measures

Primary Outcome Measures

  1. Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [Baseline, Week 12]

Secondary Outcome Measures

  1. Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  2. Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  3. Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  4. Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  5. Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  6. Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  7. Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  8. Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period [Baseline, Week 24, 52]

  9. Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  10. Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  11. Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  12. Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  13. Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 [Baseline, Week 12]

  14. Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 [Baseline, Week 12]

  15. Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [Baseline, Week 12]

  16. Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 [Baseline, Week 12]

  17. Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 [Baseline, Week 12]

  18. Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 [Baseline, Week 12]

  19. Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12 [Baseline, Week 12]

  20. Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 [Baseline, Week 12]

  21. Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  22. Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 [Baseline, Week 12, 24, 52]

  23. Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 [Week 12, 24, 52]

  24. Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 [Week 12, 24, 52]

  25. Plasma Concentration Versus Time Summary of PF-04950615 [Week 12, 24, 52]

  26. Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions [Baseline up to end of study (up to 110 weeks)]

    Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure.

  27. Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period [Baseline up to Week 58]

    Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log 2) unit was considered to be ADA positive and nAb titer >=1.58 (log 2) unit was considered to be nAb positive.

  28. Number of Participants Who Changed Concomitant Medication During Extension Period [Week 58 follow-up to Week 110]

    In this outcome measure, total number of participants who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported.

  29. Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period [Baseline, Week 58 (follow up), 71, 84, 97, 110]

  30. Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period [Week 58 (follow-up), Week 71, Week 84, Week 97, Week 110]

    Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 log2 unit was considered to be ADA positive and nAb titer >=1.58 log2 unit was considered to be nAb positive.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Treated with a statin

  • Fasting LDL-C >=100 mg/dL and triglyceride <= 400 mg/dL

  • High or very high risk of incurring a cardiovascular event

Exclusion Criteria:

  • Pregnant or breastfeeding females

  • Cardiovascular or cerebrovascular event or procedure within 90 days

  • Congestive heart failure NYHA class IV

  • Poorly controlled hypertension

Contacts and Locations

Locations

Site City State Country Postal Code
1 Advanced Cardiovascular, LLC Research Alexander City Alabama United States 35010
2 Advanced Cardiovascular, LLC, Research Auburn Alabama United States 36830
3 Clinical Research Advantage, Inc./Family Practice Specialists, Ltd. Phoenix Arizona United States 85018
4 Clinical Research Advantage, Inc./Family Practice Specialists, LTD Phoenix Arizona United States 85018
5 Radiant Research, Inc. Tucson Arizona United States 85712
6 Radiant Research, Inc Tucson Arizona United States 85712
7 Lynn Institute of the Ozarks Little Rock Arkansas United States 72205
8 The Office of Larry Watkins, MD Little Rock Arkansas United States 72205
9 American Institute of Research Los Angeles California United States 90017
10 lntermed Group Los Angeles California United States 90017
11 IMD Medical Group Los Angeles California United States 90020
12 The Office of Lucita M. Cruz, M.D., Inc. Norwalk California United States 90650
13 Superior Research, LLC Sacramento California United States 95825
14 Superior Research ,LLC Sacramento California United States 95831
15 Radiant Research, Inc. Santa Rosa California United States 95405
16 Orange County Research Center Tustin California United States 92780
17 Ventura Clinical Trials Ventura California United States 93003
18 University of Colorado Hospital Aurora Colorado United States 80045
19 Clinical Research Advantage, Inc. / Colorado Springs Family Practice Colorado Springs Colorado United States 80909
20 Creekside Endocrine Associates, PC Denver Colorado United States 80209
21 Boca Raton Clinical Research Associates Boca Raton Florida United States 33432
22 BRCR Medical Center, Inc. Boca Raton Florida United States 33432
23 Meridien Research Brooksville Florida United States 34601
24 Linfritz Research Institute Inc. Coral Gables Florida United States 33134
25 Florida Health Center Fort Lauderdale Florida United States 33312
26 Health Care Family Rehab & Research Center Hialeah Florida United States 33012
27 Indago Research & Health Center, Inc. Hialeah Florida United States 33012
28 NewPhase Clinical Trials, Corp. Miami Beach Florida United States 33140
29 Panax Clinical Research Miami Lakes Florida United States 33014
30 Precision Research Organization Miami Lakes Florida United States 33016
31 Sunrise Research Institute, Inc Miami Florida United States 33130
32 Prestige Clinical Research Center, Inc. Miami Florida United States 33133
33 Suncoast Research Group, LLD Miami Florida United States 33135
34 Elite Clinical Research Miami Florida United States 33144
35 Advanced Clinical Research of Miami Miami Florida United States 33155
36 The Research Specialists of Florida, Inc. Miami Florida United States 33162
37 Columbus Clinical Services, LLC Miami Florida United States 33165
38 First Quality Miramar Florida United States 33025
39 American Family Medical Ocala Florida United States 34471
40 Renstar Medical Research Ocala Florida United States 34471
41 Andres Patron, D.O.P.A. Pembroke Pines Florida United States 33026
42 Pines Care Research Center, LLC Pembroke Pines Florida United States 33026
43 DBC Research USA Pembroke Pines Florida United States 33029
44 Progressive Medical Research Port Orange Florida United States 32127
45 Accord Clinical Research, Llc Port Orange Florida United States 32129
46 East Coast Institute for Research, LLC/ Baker-Gilmour Cardiovascular Institute Saint Augustine Florida United States 32086
47 East Coast Institute for RSCH, St. Augustine Cardiology Associates, Research Saint Augustine Florida United States 32086
48 Meridien Research Saint Petersburg Florida United States 33709
49 Cardiovascular Center of Sarasota Sarasota Florida United States 34239
50 Meridien Research Tampa Florida United States 33634
51 Northwest Clinical Trials, Inc. Boise Idaho United States 83704
52 American Health Network of Indiana, LLC Avon Indiana United States 46123
53 Heartland Research Associates, LLC Augusta Kansas United States 67010
54 Heartland Research Associates, LLC Wichita Kansas United States 67205
55 Northwest Family Physicians Wichita Kansas United States 67205
56 Heartland Research Associates, LLC Wichita Kansas United States 67207
57 Imperial Health, LLP Lake Charles Louisiana United States 70601
58 Crescent City Clinical Research Center, LLC Metairie Louisiana United States 70006
59 Clinical Trials of America LA Monroe Louisiana United States 71201
60 Bethesda Health Research Bethesda Maryland United States 208174
61 Centennial Medical Group Elkridge Maryland United States 21075
62 McLaren Flint Flint Michigan United States 48532
63 CentraCare Heart & Vascular Center @ St. Cloud Hospital Saint Cloud Minnesota United States 56303
64 CentraCare Heart & Vascular Center at St. Cloud Hospital Saint Cloud Minnesota United States 56303
65 Riser Medical Research Picayune Mississippi United States 39466
66 Washington University, The Center for Advanced Medicine Saint Louis Missouri United States 63110
67 Washington University School of Medicine Saint Louis Missouri United States
68 Clinical Research Advantage, Inc. (Prairie Fields Family Medicine, PC) Fremont Nebraska United States 68025
69 ActivMed Practices & Research, Inc. Portsmouth New Hampshire United States 03801
70 Albuquerque Clinical Trials, Inc. Albuquerque New Mexico United States 87102
71 Physician's East Endocrinology Greenville North Carolina United States 27834
72 Physician's East P.A. Greenville North Carolina United States 27834
73 Physician's East, PA Greenville North Carolina United States 27834
74 Catawba Valley Medical Group, Inc. Hickory North Carolina United States 28601
75 Clinical Trials of America, Inc. Hickory North Carolina United States 28601
76 PMG Research of Hickory Hickory North Carolina United States 28602
77 Wake Internal Medicine Consultants, Inc. Raleigh North Carolina United States 27612
78 Wake Research Associates, LLC Raleigh North Carolina United States 27612
79 Primed Clinical Research Dayton Ohio United States 45419
80 Office of Daniel G. Williams, MD Perrysburg Ohio United States 43551
81 South Oklahoma Heart Research, LLC Oklahoma City Oklahoma United States 73135
82 Castlerock Clinical Research Consultants,LLC Tulsa Oklahoma United States 74136
83 Harleysville Medical Associates Harleysville Pennsylvania United States 19438
84 Berks Cardiologists, Ltd. Wyomissing Pennsylvania United States 19610
85 Medical Research South, LLC Charleston South Carolina United States 29407
86 Ellipsis Research Group, LLC Columbia South Carolina United States 29204
87 Spartanburg Medical Research Spartanburg South Carolina United States 29303
88 Stern Cardiovascular Foundation, Inc Germantown Tennessee United States 38138
89 Apex Cardiology Jackson Tennessee United States 38301
90 Research Associates of Jackson Jackson Tennessee United States 38301
91 PMG Research, Inc d/b/a PMG Research of Knoxville Knoxville Tennessee United States 37912
92 Punzi Medical Center Carrollton Texas United States 75006
93 Juno Research, LLC Houston Texas United States 77036
94 Gulf Coast Medical Research,LLC Houston Texas United States 77081
95 Office of Michelle Zaniewski MD., PA. Houston Texas United States 77090
96 Juno Research, LLC Katy Texas United States 77450
97 Gulf Coast Medical Research, LLC Missouri City Texas United States 77459
98 Clinical Research Advantage, Inc./ Plano Internal Medicine Associates Plano Texas United States 75093
99 Clinical Trials of Texas, Inc. San Antonio Texas United States 78205
100 Gulf Coast Medical Research, LLC Sugar Land Texas United States 77478
101 Aspen Clinical Research Orem Utah United States 84058
102 Millennium Clinical Trials, LLC Arlington Virginia United States 22207
103 National Clinical Research-Norfolk, Inc. Norfolk Virginia United States 23502
104 Sound Health Care Center Port Orchard Washington United States 98366
105 Sound Medical Research Port Orchard Washington United States 98366
106 Walla Walla Clinic Walla Walla Washington United States 99362
107 Clinical Investigation Specialists, Inc. Kenosha Wisconsin United States 53142
108 HFM Heart and Vascular Center/Holy Family Memorial, Inc Manitowoc Wisconsin United States 54220
109 LMC Clinical Research Inc. (Calgary) Calgary Alberta Canada T2H 2G4
110 Office of Dr. Ronald Collette MD Burnaby British Columbia Canada V5G 1T4
111 Medical Arts Health Research Group Kamloops British Columbia Canada V2C 1K7
112 The Medical Arts Health Research Group Kelowna British Columbia Canada V1Y 1V6
113 Glover Medical Clinic Langley British Columbia Canada V3A 4H9
114 Fraser Clinical Trials New Westminster British Columbia Canada V3L 3W4
115 The Medical Arts Health Research Group Penticton British Columbia Canada V2A 5C8
116 The Office of James K. Lai, MD Inc. Vancouver British Columbia Canada V5Z 1K3
117 Cook Street Medical Clinic Victoria British Columbia Canada V8V 4A1
118 LMC Clinical Research Inc. (Barrie) Barrie Ontario Canada L4M 7G1
119 LMC Clinical Research Inc. (Brampton) Brampton Ontario Canada L6S 0C9
120 Aggarwal And Associates Ltd Brampton Ontario Canada L6T 0G1
121 Corunna Medical Research Centre Corunna Ontario Canada N0N 1G0
122 LMC Clinical Research Inc. (Etobicoke) Etobicoke Ontario Canada M9R 4E1
123 LMC Clinical Research Inc. (Markham) Markham Ontario Canada L6B 0P9
124 SKDS Research Inc. Newmarket Ontario Canada L3Y 5G8
125 LMC Clinical Research Inc. (Oakville) Oakville Ontario Canada L6M 1M1
126 The Office of Dr. James Cha Oshawa Ontario Canada L1J 2K1
127 Kawartha Cardiology Clinical Trials Peterborough Ontario Canada K9J 0B2
128 Scarborough Cardiology Research Scarborough Ontario Canada M1E 5E9
129 LMC Clinical Research Inc. (Thornhill) Thornhill Ontario Canada L4J 8L7
130 Rouge Valley Health System - Centenary Toronto Ontario Canada M1E 4B9
131 LMC Clinical Research Inc. (Bayview) Toronto Ontario Canada M4G 3E8
132 Manna Research Inc. Toronto Ontario Canada M9W 4L6
133 Ecogene-21 Chicoutimi Quebec Canada G7H 7K9
134 ViaCar Recherche Clinique Inc. Greenfield Park Quebec Canada J4V 2G8
135 Centre de Depistage et de Recherche Cardiovasculaire Rive-Sud Longueuil Quebec Canada J4M2X1
136 Montreal Heart Institute Montreal Quebec Canada H1T 1C8
137 Centre De Sante Et De Services Sociaux De Beauce (CSSSB) Saint-Georges, Beauce Quebec Canada G5Y 4T8
138 C.I.C. Maurice Inc. Trois-Rivieres Quebec Canada G8T 7A1
139 C.I.C. Mauricie Inc. Trois-Rivieres Quebec Canada G8T 7A1
140 Clinique des maladies lipidiques de Quebec Quebec Canada G1V 4W2
141 Alpha Recherche Clinique Quebec Canada G3K 2P8
142 Kardiologicka ambulance Trutnov Kralovehradecky KRAJ Czechia 54101
143 Fakultni Nemocnice Kralovske Vinohrady, II. interni klinika Praha 10 Vinohrady Czechia 100 34
144 Fakultni nemocnice u sv. Anny Brno. Oddeleni klinicke biochemie Brno Czechia 656 91
145 Fakultni nemocnice u sv. Anny. Nemoenicni lekarna (pharmacy) Brno Czechia 656 91
146 Cardiocentrum Kladno s.r.o., Kardiologicka ambulance Kladno Czechia 27280
147 Lekarna - P-P Klinika Kladno Kladno Czechia 27280
148 Lunacor s.r.o. Kromeriz Czechia 76701
149 Fakultni Nemocnice Olomouc, III. interni klinika ¿ nefrologicka, revmatologicka a endokrinologicka Olomouc Czechia 775 20
150 Lekarna Fakultni nemocnice Olomouc (pharmacy) Olomouc Czechia 77520
151 Lekarna Domovina Olomouc Czechia 779 00
152 PreventaMed, s.r.o. Olomouc Czechia 779 00
153 IKEM, Oddeleni preventivni kardiologie Praha 4 Czechia 140 21
154 IKEM, Ustavni lekarna Praha 4 Czechia 140 21
155 BENU lekarna Pribram Czechia 261 01
156 Kardiologicka ambulance, III. Poliklinika Pribram Czechia 261 01
157 Lekarna 203-02 Slany Czechia 274 01
158 Nemocnice Slany, Interni oddeleni Slany Czechia 274 01
159 AeskuLab k.s., Lipidova poradna Teplice Czechia 415 01
160 Lekarna Centrum (pharmacy) Teplice Czechia 415 01
161 Dr.Max lekarna Trutnov Czechia 541 01
162 Etela-Karjalan Keskussairaala Lappeenranta Finland 53130
163 Turku University Hospital Turku Finland 20520
164 Sacred Heart Hospital-Hallym University Anyang-si Gyeonggi-do Korea, Republic of 431-796
165 Hanyang University Guri Hospital Guri-si Gyeonggi-do Korea, Republic of 11923
166 Dong-A University Hospital Busan Korea, Republic of 49201
167 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 137-701
168 Medisch Spectrum Twente Enschede ER Netherlands 7513
169 St Lucas Andreas Hospital Amsterdam North Holland Netherlands 1061 AE
170 Gelre Hospitals Apeldoorn Netherlands 7334 DZ
171 Andromed Eindhoven Eindhoven Netherlands 5611 NV
172 Medisch Spectrum Twente Enschede Netherlands 7513 ER
173 Beatrix Hospital Gorinchem Netherlands 4204 AA
174 Martini Ziekenhuis Groningen Netherlands 9728 NT
175 Zuyderland Medisch Centrum Heerlen Netherlands 6419 PC
176 Andro Medical Research B.V. Rotterdam Netherlands 3021 HC
177 Ikazia Hospital Rotterdam Netherlands 3083AN
178 D&A Research and Genetics Sneek Netherlands 8601 ZR
179 St. Elisabeth Hospital Tilburg Netherlands 5022 GC
180 University Medical Center Utrecht Utrecht Netherlands 3584 CX
181 Ossum Gronert Legetjeneste AS Honefoss Norway 3515
182 Oslo Universitetssykehus HF Oslo Norway 0373
183 Oslo Universitetssykehus HF, Ulleval Oslo Norway 0424
184 KO-MED Centra Kliniczne Lublin Lublin Lubelskie Poland 20-362
185 KO-MED Centra Kliniczne Zamosc Zamosc Lubelskie Poland 22-400
186 KO-MED. Centra Kliniczne Staszow Staszow Swietokrzyskie Poland 28-200
187 Synexus Polska Sp. z o.o. Oddzial w Gdyni Gdynia Poland 81-384
188 MCBK Sc lwona Czajkowska Monika Barney Grodzisk Mazowiecki Poland 05-825
189 Synexus Polska Sp. z o. o. Oddizial w Katowicach. Katowice Poland 40-040
190 Clinport Tura Lipinska Dabrowski S.C. Katowice Poland 40-084
191 Krakowski Szpital Specjalistyczny im. Jana Pawla II Krakow Poland 31-202
192 Jan Zbigniew Peruga NZOZ SALUS Lodz Poland 91-302
193 Zespol Opieki Zdrowotnej W Olawie, Oddzial Chorob Wewnetrznych Olawa Poland 55-200
194 Synexus Polska Sp. z o.o Oddzial w Poznaniu Poznan Poland 60-702
195 KO-MED Centra Kliniczne Sp. z o.o. Pulawy Poland 24-100
196 Synexus Polska Sp. z o.o. Oddzial w Warszawie Warszawa Poland 01-192
197 Synexus Polska Sp. z o.o. Oddzial we Wroclawiu Wroclaw Poland 50-088
198 .WroMedica Irena Bielicka, Janusz Szczepanik Spolka Cywlina Wroclaw Poland 51-685
199 Ponce School Of Medicine Ponce Puerto Rico 00716
200 Cardiometabolic Research Center, Inc Ponce Puerto Rico 00717
201 Caparra Internal Medicine Rio Grande Puerto Rico 00745
202 National University Hospital Singapore Singapore 119228
203 National Heart Centre Singapore Singapore Singapore 169609
204 Clinical Trial Center (CTC)/Centrum foer klinisk proevning Goteborg Sweden 413 45
205 Vardcentralen Lessebo Lessebo Sweden 360 50
206 Clinical Trials Consultants AB Linkoping Sweden 58758
207 ProbarE i Lund AB Lund Sweden 222 22
208 Capio Citykliniken Hjartmottagning Lund Sweden 22221
209 Dalecarlia Clinical Research Center Rattvik Sweden 79530
210 Citydiabetes Stockholm Sweden 111 57
211 Karolinska Universitetssjukhuset Huddinge Stockholm Sweden 141 86
212 Synexus Thames Valley Clinical Research Centre Reading Berkshire United Kingdom RG2 0TG
213 Salford Royal NHS Foundation Trust Salford Greater Manchester United Kingdom M6 8HD
214 Synexus Scotland Clinical Research Centre Glasgow Lanarkshire Scotland United Kingdom G20 0SP
215 Synexus Lancashire Clinical Research Centre Chorley Lancashire United Kingdom PR7 7NA
216 Synexus North East Clinical Research Centre - Hexham General Hospital Hexham Northumberland United Kingdom NE46 1QJ
217 Worcestershire Acute Hospitals NHS Trust - Worcestershire Royal Hospital Worcester Worcestershire United Kingdom WR5 1DD
218 University Hospital Ayr - Nhs Ayrshire And Arran Ayr United Kingdom KA6 6DX
219 Synexus Midlands Clinical Research Centre Birmingham United Kingdom B15 2SQ
220 Hull and East Yorkshire Hospitals NHS Trust Hull United Kingdom HU3 2JZ
221 Synexus Merseyside Clinical Research Centre Liverpool United Kingdom L22 0LG
222 Synexus Manchester Clinical Research Centre Manchester United Kingdom M15 6SX
223 Abertawe Bro Morgannwg University Local Health Board Joint Clinical Research Facility, Swansea United Kingdom SA2 8PP

Sponsors and Collaborators

  • Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02100514
Other Study ID Numbers:
  • B1481045
  • SPIRE-LL
  • 2014-000478-20
First Posted:
Apr 1, 2014
Last Update Posted:
Jul 31, 2018
Last Verified:
Jul 1, 2018
Keywords provided by Pfizer
Primary hyperlipidemia or mixed dyslipidemia
high risk of cardiovascular events
multiple cardiovascular disease risk factors.
Additional relevant MeSH terms:
Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Bococizumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail This study was conducted at multiple sites from 28 October 2014 to 15 July 2016 for the treatment period and up to 10 July 2017 for the extension period.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 milligram (mg) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, participants who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 (log2) units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Participants who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
Period Title: Treatment Period
STARTED 247 499 0 0 0
COMPLETED 218 425 0 0 0
NOT COMPLETED 29 74 0 0 0
Period Title: Treatment Period
STARTED 0 0 44 33 56
COMPLETED 0 0 42 33 56
NOT COMPLETED 0 0 2 0 0

Baseline Characteristics

Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Total
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Total of all reporting groups
Overall Participants 247 499 746
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
61.7
(10.0)
61.5
(9.9)
61.6
(9.9)
Sex: Female, Male (Count of Participants)
Female
107
43.3%
223
44.7%
330
44.2%
Male
140
56.7%
276
55.3%
416
55.8%

Outcome Measures

1. Primary Outcome
Title Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "Number of participants analyzed (N)" signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 235 468
Mean (Standard Deviation) [percent change]
-0.8
(17.61)
-50.8
(29.81)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Least square (LS) mean difference and associated 95% confidence interval (CI), and p-value were derived from an mixed effect model repeat measurement (MMRM) model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -49.9
Confidence Interval (2-Sided) 95%
-54.0 to -45.8
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.09
Estimation Comments
2. Secondary Outcome
Title Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at the specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-2.2
(13.41)
-35.4
(20.93)
Week 24
-3.1
(15.79)
-32.9
(23.06)
Week 52
-5.0
(17.22)
-29.0
(22.08)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -33.2
Confidence Interval (2-Sided) 95%
-36.1 to -30.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.48
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -29.6
Confidence Interval (2-Sided) 95%
-32.8 to -26.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.66
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -23.8
Confidence Interval (2-Sided) 95%
-27.0 to -20.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.65
Estimation Comments
3. Secondary Outcome
Title Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at the specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-0.6
(16.70)
-46.5
(28.87)
Week 24
-2.1
(18.66)
-43.5
(32.26)
Week 52
-4.4
(20.77)
-37.3
(29.59)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI, and p-value were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -45.7
Confidence Interval (2-Sided) 95%
-49.7 to -41.7
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.04
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI, were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -40.9
Confidence Interval (2-Sided) 95%
-45.3 to -36.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.26
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI, were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -32.5
Confidence Interval (2-Sided) 95%
-36.7 to -28.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.17
Estimation Comments
4. Secondary Outcome
Title Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at the specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-2.6
(17.57)
-47.6
(28.36)
Week 24
-3.8
(20.63)
-44.7
(30.83)
Week 52
-6.4
(22.70)
-39.5
(29.36)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -45.0
Confidence Interval (2-Sided) 95%
-48.9 to -41.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.99
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -40.5
Confidence Interval (2-Sided) 95%
-44.8 to -36.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.21
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -32.7
Confidence Interval (2-Sided) 95%
-37.0 to -28.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.20
Estimation Comments
5. Secondary Outcome
Title Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
A subset of FAS included all participants who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of participants who were evaluable at the specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 164 331
Week 12
0.5
(16.61)
-51.1
(30.43)
Week 24
-1.6
(21.68)
-48.4
(33.67)
Week 52
-4.2
(24.11)
-42.2
(33.75)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -51.6
Confidence Interval (2-Sided) 95%
-56.7 to -46.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.59
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -46.4
Confidence Interval (2-Sided) 95%
-52.2 to -40.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.94
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -37.4
Confidence Interval (2-Sided) 95%
-43.3 to -31.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.03
Estimation Comments
6. Secondary Outcome
Title Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
A subset of FAS included all participants who were randomized and had TG >=200 mg/dL at pre-randomization. Here, "n" signifies number of participants evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 83 168
Week 24
-5.7
(21.67)
-45.8
(33.13)
Week 52
-5.7
(23.78)
-40.9
(30.25)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -46.6
Confidence Interval () 95%
-53.7 to -39.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.59
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -39.7
Confidence Interval () 95%
-47.9 to -31.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.12
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -33.4
Confidence Interval () 95%
-41.3 to -25.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.02
Estimation Comments
7. Secondary Outcome
Title Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at the specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
4.9
(54.24)
-25.7
(29.45)
Week 24
5.9
(50.52)
-21.3
(34.42)
Week 52
27.9
(374.64)
-21.5
(32.61)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -30.8
Confidence Interval () 95%
-36.9 to -24.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.14
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -27.5
Confidence Interval () 95%
-33.9 to -21.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.23
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -49.4
Confidence Interval (2-Sided) 95%
-85.2 to -13.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 18.27
Estimation Comments
8. Secondary Outcome
Title Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
0.6
(13.93)
6.3
(13.86)
Week 24
0.6
(14.88)
6.3
(14.49)
Week 52
0.7
(14.24)
7.0
(15.60)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method MMRM
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 5.5
Confidence Interval (2-Sided) 95%
3.4 to 7.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.06
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 5.4
Confidence Interval () 95%
3.2 to 7.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.14
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 6.0
Confidence Interval () 95%
3.6 to 8.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.20
Estimation Comments
9. Secondary Outcome
Title Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period
Description
Time Frame Baseline, Week 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 24
-2.9
(21.72)
-47.5
(33.48)
Week 52
-4.7
(23.96)
-41.8
(32.67)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -44.2
Confidence Interval () 95%
-48.8 to -39.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.39
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -36.2
Confidence Interval (2-Sided) 95%
-40.9 to -31.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.42
Estimation Comments
10. Secondary Outcome
Title Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-6.2
(32.92)
-16.2
(32.86)
Week 24
-8.9
(35.60)
-18.2
(65.13)
Week 52
-8.0
(41.46)
-15.8
(35.57)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -10.1
Confidence Interval () 95%
-15.1 to -5.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.55
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -9.0
Confidence Interval () 95%
-17.9 to -0.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.50
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -8.2
Confidence Interval () 95%
-14.1 to -2.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.04
Estimation Comments
11. Secondary Outcome
Title Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-0.9
(11.09)
3.4
(11.43)
Week 24
-1.6
(10.81)
2.5
(11.61)
Week 52
-1.0
(13.12)
3.4
(11.77)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 4.1
Confidence Interval () 95%
2.5 to 5.8
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.85
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 3.8
Confidence Interval () 95%
2.2 to 5.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.86
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 4.3
Confidence Interval () 95%
2.4 to 6.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.97
Estimation Comments
12. Secondary Outcome
Title Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
2.0
(11.94)
3.0
(11.94)
Week 24
2.6
(12.12)
3.7
(14.12)
Week 52
0.7
(12.46)
1.9
(12.22)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 1.1
Confidence Interval () 95%
-0.7 to 2.8
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.90
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 0.9
Confidence Interval () 95%
-1.1 to 3.0
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.04
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 0.8
Confidence Interval () 95%
-1.0 to 2.7
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.95
Estimation Comments
13. Secondary Outcome
Title Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
-6.2
(32.92)
-16.2
(32.86)
Week 24
-8.9
(35.60)
-18.2
(65.13)
Week 52
-8.0
(41.46)
-15.8
(35.57)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -10.1
Confidence Interval () 95%
-15.1 to -5.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.55
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -9.0
Confidence Interval () 95%
-17.9 to -0.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.50
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -8.2
Confidence Interval () 95%
-14.1 to -2.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.04
Estimation Comments
14. Secondary Outcome
Title Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
A subset of FAS included all participants who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of participants evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 164 331
Baseline
130.1
(25.22)
130.2
(28.72)
Change at Week 12
-0.5
(22.37)
-67.3
(40.14)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -66.8
Confidence Interval () 95%
-73.0 to -60.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.18
Estimation Comments
15. Secondary Outcome
Title Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
A subset of FAS included all participants who were randomized and had TG >=200 mg/dL at pre-randomization. Here, "n" signifies number of participants evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 83 168
Baseline
143.7
(35.49)
147.2
(39.48)
Change at Week 12
-6.6
(29.61)
-74.1
(48.04)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -66.1
Confidence Interval () 95%
-76.7 to -55.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.40
Estimation Comments
16. Secondary Outcome
Title Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
134.7
(29.71)
135.9
(33.67)
Change at Week 12
-2.5
(25.07)
-69.6
(42.98)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -66.5
Confidence Interval () 95%
-72.0 to -61.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.77
Estimation Comments
17. Secondary Outcome
Title Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
209.4
(33.84)
210.3
(37.97)
Change at Week 12
-5.9
(29.61)
-75.4
(46.91)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -69.1
Confidence Interval () 95%
-75.2 to -63.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.08
Estimation Comments
18. Secondary Outcome
Title Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
160.2
(33.49)
162.1
(37.78)
Change at Week 12
-5.8
(29.59)
-77.9
(48.28)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -71.3
Confidence Interval () 95%
-77.5 to -65.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.14
Estimation Comments
19. Secondary Outcome
Title Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
106.1
(20.43)
107.1
(23.33)
Change at Week 12
-1.6
(18.09)
-49.8
(31.81)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -47.7
Confidence Interval () 95%
-51.9 to -43.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.12
Estimation Comments
20. Secondary Outcome
Title Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
48.5
(54.04)
47.3
(53.55)
Change at Week 12
0.1
(10.91)
-10.3
(17.01)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -10.4
Confidence Interval () 95%
-12.5 to -8.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.06
Estimation Comments
21. Secondary Outcome
Title Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Description
Time Frame Baseline, Week 12

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
49.2
(13.20)
48.3
(11.60)
Change at Week 12
-0.1
(6.75)
2.5
(6.64)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value 2.6
Confidence Interval () 95%
1.6 to 3.6
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.52
Estimation Comments
22. Secondary Outcome
Title Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
4.6
(1.90)
4.6
(1.31)
Change at Week 12
-0.2
(1.27)
-1.8
(1.29)
Change at Week 24
-0.2
(1.42)
-1.6
(1.38)
Change at Week 52
-0.2
(1.62)
-1.5
(1.32)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -1.6
Confidence Interval () 95%
-1.8 to -1.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.08
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -1.4
Confidence Interval () 95%
-1.6 to -1.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.10
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -1.4
Confidence Interval () 95%
-1.6 to -1.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.12
Estimation Comments
23. Secondary Outcome
Title Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
Description
Time Frame Baseline, Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, "n" signifies number of participants evaluable at specified time points.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Baseline
0.7
(0.25)
0.8
(0.22)
Change at Week 12
0.0
(0.14)
-0.4
(0.25)
Change at Week 24
-0.0
(0.16)
-0.3
(0.27)
Change at Week 52
0.0
(0.66)
-0.3
(0.25)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -0.4
Confidence Interval () 95%
-0.4 to -0.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.02
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -0.3
Confidence Interval () 95%
-0.3 to -0.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.02
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter LS mean difference compared to placebo
Estimated Value -0.3
Confidence Interval () 95%
-0.4 to -0.2
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.04
Estimation Comments
24. Secondary Outcome
Title Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Description
Time Frame Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, 'n' signifies those participants who were evaluable at specified time points for each arm respectively.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
10.2
4.1%
81.6
16.4%
Week 24
19.9
8.1%
75.1
15.1%
Week 52
25.2
10.2%
72.7
14.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 53.9
Confidence Interval () 95%
32.08 to 90.59
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 17.0
Confidence Interval () 95%
11.15 to 26.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.1
Confidence Interval () 95%
6.18 to 13.48
Parameter Dispersion Type:
Value:
Estimation Comments
25. Secondary Outcome
Title Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Description
Time Frame Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
FAS included all participants who were randomized. Here, 'n' signifies those participants who were evaluable at specified time points for each arm respectively.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
Week 12
1.3
0.5%
62.2
12.5%
Week 24
1.7
0.7%
60.1
12%
Week 52
3.2
1.3%
53.4
10.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 156.4
Confidence Interval () 95%
48.84 to 501.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 110.8
Confidence Interval () 95%
39.77 to 308.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treatment Period: Placebo, Treatment Period: Bococizumab 150 mg
Comments Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 43.3
Confidence Interval () 95%
19.52 to 96.13
Parameter Dispersion Type:
Value:
Estimation Comments
26. Secondary Outcome
Title Plasma Concentration Versus Time Summary of PF-04950615
Description
Time Frame Week 12, 24, 52

Outcome Measure Data

Analysis Population Description
Analysis set included participants who received at least 1 dose of PF-04950615. This outcome measure was planned not to be analysed for placebo reporting arm. Here, "n" signifies those participants who were evaluable at specified time points.
Arm/Group Title Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 499
Week 12
5.37
(5.327)
Week 24
5.28
(5.888)
Week 52
4.01
(4.652)
27. Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions
Description Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure.
Time Frame Baseline up to end of study (up to 110 weeks)

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 247 499
With type 1 or 3 hypersensitivity reactions
0.0
0%
0.2
0%
With injection site reactions
0.8
0.3%
13.4
2.7%
28. Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period
Description Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log 2) unit was considered to be ADA positive and nAb titer >=1.58 (log 2) unit was considered to be nAb positive.
Time Frame Baseline up to Week 58

Outcome Measure Data

Analysis Population Description
Analysis set included all participants who received at least 1 dose of PF-04950615 150 mg. This outcome measure was planned not to be analysed for placebo reporting arm. Here "N" signifies number of subjects who were evaluable for this outcome measure.
Arm/Group Title Treatment Period: Bococizumab 150 mg
Arm/Group Description Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58.
Measure Participants 491
Baseline up to Week 58: ADA positive
54.8
22.2%
Baseline up to Week 58: nAb positive
37.9
15.3%
29. Secondary Outcome
Title Number of Participants Who Changed Concomitant Medication During Extension Period
Description In this outcome measure, total number of participants who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported.
Time Frame Week 58 follow-up to Week 110

Outcome Measure Data

Analysis Population Description
All participants who consented for extension period.
Arm/Group Title Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Arm/Group Description Participants randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, participants who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 (log2) units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Participants who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
Measure Participants 44 33 56
Count of Participants [Participants]
2
0.8%
4
0.8%
3
0.4%
30. Secondary Outcome
Title Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period
Description
Time Frame Baseline, Week 58 (follow up), 71, 84, 97, 110

Outcome Measure Data

Analysis Population Description
All participants who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms: Placebo (Extension Period) and Bococizumab ADA negative (Extension Period).
Arm/Group Title Extension Period: Bococizumab ADA Positive
Arm/Group Description Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, participants who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 (log2) units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
Measure Participants 33
Week 58 (follow up)
6.7
(27.70)
Week 71
8.7
(34.83)
Week 84
7.0
(30.34)
Week 97
2.6
(31.43)
Week 110
15.5
(36.17)
31. Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period
Description Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 log2 unit was considered to be ADA positive and nAb titer >=1.58 log2 unit was considered to be nAb positive.
Time Frame Week 58 (follow-up), Week 71, Week 84, Week 97, Week 110

Outcome Measure Data

Analysis Population Description
All participants who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms Placebo (Extension period) and Bococizumab ADA negative (Extension period). Here, "n" signifies number of participants who were evaluable at specified time points.
Arm/Group Title Extension Period: Bococizumab ADA Positive
Arm/Group Description Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, participants who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 (log2) units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
Measure Participants 33
Week 58 (follow up): ADA positive
100.0
40.5%
Week 58 (follow up): nAB positive
60.6
24.5%
Week 71: ADA positive
87.1
35.3%
Week 71: nAB positive
35.5
14.4%
Week 84: ADA positive
82.1
33.2%
Week 84: nAB positive
25.0
10.1%
Week 97: ADA positive
86.4
35%
Week 97: nAB positive
18.2
7.4%
Week 110: ADA positive
100.0
40.5%
Week 110: nAB positive
11.8
4.8%

Adverse Events

Time Frame For SAEs: Baseline up to Week 110 and for other AEs: Baseline up to Week 58
Adverse Event Reporting Description Event may be serious in 1 and nonserious in other participant or 1 participant may have experienced both serious and nonserious AE. Participants evaluable:treatment period: participants who received at least 1 dose of study drug;extension period: participants who consented for extension period. Nonserious AEs were not collected for extension period.
Arm/Group Title Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Arm/Group Description Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. Participants randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, participants who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 (log2) units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110. Participants randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Participants who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
All Cause Mortality
Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/247 (0.8%) 2/499 (0.4%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Serious Adverse Events
Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 32/247 (13%) 44/499 (8.8%) 2/44 (4.5%) 0/33 (0%) 1/56 (1.8%)
Blood and lymphatic system disorders
Anaemia 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Cardiac disorders
Acute myocardial infarction 2/247 (0.8%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Angina pectoris 1/247 (0.4%) 3/499 (0.6%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Angina unstable 2/247 (0.8%) 4/499 (0.8%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Arrhythmia 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Atrial fibrillation 0/247 (0%) 2/499 (0.4%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Cardiac failure 2/247 (0.8%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Coronary artery disease 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Coronary artery occlusion 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Left ventricular failure 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Myocardial infarction 3/247 (1.2%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Sinus bradycardia 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Sinus node dysfunction 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Ventricular tachycardia 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Atrial fibrillation 0/247 (0%) 0/499 (0%) 1/44 (2.3%) 0/33 (0%) 0/56 (0%)
Myocardial ischaemia 0/247 (0%) 0/499 (0%) 1/44 (2.3%) 0/33 (0%) 0/56 (0%)
Ear and labyrinth disorders
Sudden hearing loss 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Eye disorders
Cataract 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Gastrointestinal disorders
Abdominal hernia 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Diverticulum intestinal 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Duodenal ulcer 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Gastric ulcer 2/247 (0.8%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Gastrooesophageal reflux disease 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Intestinal obstruction 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Oesophageal perforation 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Small intestinal obstruction 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
General disorders
POSSIBLE SEIZURE DISORDER SECONDARY TO AMPHETAMINE ABUSE 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Asthenia 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Chest pain 1/247 (0.4%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Complication associated with device 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Death 1/247 (0.4%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Non-cardiac chest pain 0/247 (0%) 5/499 (1%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Pyrexia 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Vascular stent occlusion 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Hepatobiliary disorders
Cholecystitis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Infections and infestations
Arthritis bacterial 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Diverticulitis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Gangrene 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Infected skin ulcer 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Klebsiella sepsis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Pneumonia 1/247 (0.4%) 2/499 (0.4%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Postoperative wound infection 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Sepsis 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Urinary tract infection 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Urosepsis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Injury, poisoning and procedural complications
Arterial injury 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Investigations
Gamma-glutamyltransferase increased 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Metabolism and nutrition disorders
Hypoglycaemia 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Musculoskeletal and connective tissue disorders
Arthritis 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Bursitis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Osteoarthritis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Spondyloarthropathy 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Tendonitis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Bone cancer 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Breast cancer 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Breast cancer recurrent 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Malignant melanoma 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Non-small cell lung cancer 1/247 (0.4%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Plasma cell myeloma 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Skin cancer 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Tonsil cancer 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Disease progression 0/247 (0%) 0/499 (0%) 1/44 (2.3%) 0/33 (0%) 0/56 (0%)
Nervous system disorders
Cerebral haematoma 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Cerebral haemorrhage 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Cerebrovascular accident 0/247 (0%) 3/499 (0.6%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Ischaemic stroke 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Miller Fisher syndrome 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Radiculopathy 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Subarachnoid haemorrhage 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Syncope 1/247 (0.4%) 2/499 (0.4%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Transient ischaemic attack 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Psychiatric disorders
Depression 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Depression suicidal 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Paranoia 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Psychiatric decompensation 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Suicidal behaviour 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Renal and urinary disorders
Acute kidney injury 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Chronic kidney disease 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Nephrolithiasis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Renal failure 1/247 (0.4%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Urinary retention 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Asthma 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Chronic obstructive pulmonary disease 0/247 (0%) 2/499 (0.4%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Haemoptysis 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Pulmonary embolism 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Pulmonary hypertension 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Dyspnoea 0/247 (0%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 1/56 (1.8%)
Chest pain 0/247 (0%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 1/56 (1.8%)
Skin and subcutaneous tissue disorders
Diabetic foot 0/247 (0%) 1/499 (0.2%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Vascular disorders
Aortic aneurysm 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Peripheral artery dissection 1/247 (0.4%) 0/499 (0%) 0/44 (0%) 0/33 (0%) 0/56 (0%)
Other (Not Including Serious) Adverse Events
Treatment Period: Placebo Treatment Period: Bococizumab 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA Positive Extension Period: Bococizumab ADA Negative
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 29/247 (11.7%) 97/499 (19.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
General disorders
Injection site reaction 2/247 (0.8%) 67/499 (13.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
Infections and infestations
Nasopharyngitis 14/247 (5.7%) 17/499 (3.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
Upper respiratory tract infection 14/247 (5.7%) 18/499 (3.6%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02100514
Other Study ID Numbers:
  • B1481045
  • SPIRE-LL
  • 2014-000478-20
First Posted:
Apr 1, 2014
Last Update Posted:
Jul 31, 2018
Last Verified:
Jul 1, 2018