Clinical Trials List
Protocol NumberB1481020
2013-10-23 - 2016-03-21
Phase III
Terminated5
ICD-10NoDx
0
ICD-9E942.2
Antilipaemic and antiarteriosclerotic drugs causing adverse effects in therapeutic use
A PHASE 3 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO ASSESS THE EFFICACY, LONG-TERM SAFETY AND TOLERABILITY OF PF-04950615 IN SUBJECTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA AT RISK OF CARDIOVASCULAR EVENTS
-
Sponsor
Pfizer
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/19
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Tse-Min Lu Division of General Internal Medicine
- Shih-Hsien Sung Division of General Internal Medicine
- Wen-Chung Yu Division of General Internal Medicine
- Tze-Fan Chao Division of General Internal Medicine
- 林幸榮 Division of General Internal Medicine
- Kang-Ling Wang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- JUN-SING WANG Division of General Internal Medicine
- 郭怡婷 Division of General Internal Medicine
- 傅家保 Division of General Internal Medicine
- 梁凱偉 Division of General Internal Medicine
- I-TE LEE Division of General Internal Medicine
- 陳柏勳 Division of General Internal Medicine
- 林時逸 Division of General Internal Medicine
- 李佳霖 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA
Objectives
the primaryobjective of this study is to demonstrate a superior LDL-C lowering effect of PF-04950615
150 mg administered by the SC route Q2wks compared to placebo, in subjects with primary
hyperlipidemia or mixed dyslipidemia at high and very high risk for cardiovascular (CV)
events receiving a maximally tolerated dose of statin. Secondary objectives are to
demonstrate a superior effect of PF-04950615 on Total cholesterol (TC), High density
lipoprotein cholesterol (HDL-C), Triglycerides (TG), and non HDL-C; other lipid
parameters, including apolipoprotein B(ApoB), ApoA-I, ApoA-II, lipoprotein a (Lp(a)); and
LDL-C in subjects with primary hypercholesterolemia (pre-randomization 1
triglycerides
(TG) < 200 mg/dL (2.26 mmol/L) and, in subjects with mixed dyslipidemia (prerandomization TG ≥ 200 mg/dL (2.26 mmol/L). Safety, tolerability and pharmacokinetics of
PF-04950615 will be characterized.
Test Drug
PF-04950615 (RN316)
Active Ingredient
PF-04950615 (RN316)
Dosage Form
針劑
Dosage
100
Endpoints
the primary objective of this study is to demonstrate a superior LDL-C lowering effect of PF-04950615 150 mg administered by the SC route Q2wks compared to placebo, in subjects with primary hyperlipidemia or mixed dyslipidemia at high and very high risk for cardiovascular (CV) events receiving a maximally tolerated dose of statin. Secondary objectives are to demonstrate a superior effect of PF-04950615 on Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Triglycerides (TG), and non HDL-C; other lipid parameters, including apolipoprotein B(ApoB), ApoA-I, ApoA-II, lipoprotein a (Lp(a)); and LDL-C in subjects with primary hypercholesterolemia (pre-randomization 1 triglycerides (TG) < 200 mg/dL (2.26 mmol/L) and, in subjects with mixed dyslipidemia (prerandomization TG ≥ 200 mg/dL (2.26 mmol/L). Safety, tolerability and pharmacokinetics of PF-04950615 will be characterized.
Inclution Criteria
Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:1. Evidence of a personally signed and dated informed consent document indicating that the
subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
3. Males and females 18 years of age.
4. With primary hyperlipidemia or mixed dyslipidemia.
5. Subjects are required to be treated with atorvastatin, simvastatin, or rosuvastatin at the
highest locally approved dose. If at a lower dose, there must be documentation that the
subject is receiving a maximally tolerated dose of the aforementioned statins; and no dose
should be lower than atorvastatin 20 mg, rosuvastatin 20 mg, or simvastatin 40 mg.
Subjects on simvastatin 80 mg must have been on this dose for >1 year before
screening.
All subjects must be on a stable dose at least 6 weeks prior to screening. There
should be no plans at the time of screening and randomization to modify the dose
of statin for the duration of the trial.
Source records and case report form (CRF) must show documentation of the
requirements shown above..
6. Subjects should be at high or very high risk of incurring a CV event, defined as:
a. Known CVD or CVD risk equivalents:
Known history of CVD.
Coronary heart disease: history of acute myocardial infarction, evidence of silent
myocardial infarction or myocardial ischemia, history of unstable angina and
stable angina pectoris, and history of coronary procedures (coronary angioplasty
and coronary artery surgery), or;
Other clinical atherosclerotic diseases: peripheral arterial disease, abdominal
aortic aneurysm, carotid artery disease (symptomatic [eg, transient ischemic
attack or stroke of carotid origin] or >50 percent stenosis on angiography or
ultrasound), and likely other forms of clinical atherosclerotic disease (eg, renal
artery disease),
or;
Type 2 or Type 1 diabetes, or;
Chronic kidney disease (CKD), defined as glomerular filtration rate (GFR) calculated
by Modification of Diet in Renal Disease (MDRD) formula between 30 and
60 mL/min/1.73m2
(inclusive).
b. Presence of multiple risk factors:
Subjects who do not have past CVD disease or CVD risk equivalents but have 3 or more of
the risk factors from the list below:
Current cigarette smoking defined as any smoking for 30 days or more at the time of
screening.
HDL-C <40 mg/dL (<1.0 mmol/L) at screening or TC/HDL-C ratio 6.
Family history of premature CHD (CHD in male first-degree relative <55 years; CHD
in female first-degree relative <65 years).
Age (men 55 years; women 65 years).
hs-CRP >2.0 mg/L at screening.
7. Lipids should meet the following criteria on a background treatment with a statin at the
2 screening visits:
a. Subjects with known CVD or CVD risk equivalents (Refer to 6a, above) at the highest
approved dose of statins described in 5, above:
Fasting LDL C 70 mg/dL (1.81 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Subjects not at the highest approved dose of statins described in 5, above:
Fasting LDL C 77 mg/dL (1.99 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
b. Subjects with multiple risk factors (Refer to 6b, above) at the highest approved dose of statins described in 5, above:
Fasting LDL C 100 mg/dL (2.59 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Subjects not at the highest approved dose of statins described in 5, above:
Fasting LDL C 110 mg/dL (2.85 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Fasting TG 400 mg/dL (4.51 mmol/L) at the second screening visit within 7 days of
randomization 3
.
8. Male and female subjects of childbearing potential must agree to use a highly effective
method of contraception throughout the study and for at least 63 days after the last dose
of assigned treatment. A subject is of childbearing potential if, in the opinion of the
investigator, he/she is biologically capable of having children and is sexually active
(Section 4.4.2).
Female subjects who are not of childbearing potential (ie, meet at least one of the
following criteria):
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure or;
Achieved post-menopausal status, defined as: cessation of regular menses for at
least 12 consecutive months with no alternative pathological or physiological
cause; and have a serum follicule-stimulating hormone(FSH) level within the
laboratory’s reference range for postmenopausal females.
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:1. Evidence of a personally signed and dated informed consent document indicating that the
subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
3. Males and females 18 years of age.
4. With primary hyperlipidemia or mixed dyslipidemia.
5. Subjects are required to be treated with atorvastatin, simvastatin, or rosuvastatin at the
highest locally approved dose. If at a lower dose, there must be documentation that the
subject is receiving a maximally tolerated dose of the aforementioned statins; and no dose
should be lower than atorvastatin 20 mg, rosuvastatin 20 mg, or simvastatin 40 mg.
Subjects on simvastatin 80 mg must have been on this dose for >1 year before
screening.
All subjects must be on a stable dose at least 6 weeks prior to screening. There
should be no plans at the time of screening and randomization to modify the dose
of statin for the duration of the trial.
Source records and case report form (CRF) must show documentation of the
requirements shown above..
6. Subjects should be at high or very high risk of incurring a CV event, defined as:
a. Known CVD or CVD risk equivalents:
Known history of CVD.
Coronary heart disease: history of acute myocardial infarction, evidence of silent
myocardial infarction or myocardial ischemia, history of unstable angina and
stable angina pectoris, and history of coronary procedures (coronary angioplasty
and coronary artery surgery), or;
Other clinical atherosclerotic diseases: peripheral arterial disease, abdominal
aortic aneurysm, carotid artery disease (symptomatic [eg, transient ischemic
attack or stroke of carotid origin] or >50 percent stenosis on angiography or
ultrasound), and likely other forms of clinical atherosclerotic disease (eg, renal
artery disease),
or;
Type 2 or Type 1 diabetes, or;
Chronic kidney disease (CKD), defined as glomerular filtration rate (GFR) calculated
by Modification of Diet in Renal Disease (MDRD) formula between 30 and
60 mL/min/1.73m2
(inclusive).
b. Presence of multiple risk factors:
Subjects who do not have past CVD disease or CVD risk equivalents but have 3 or more of
the risk factors from the list below:
Current cigarette smoking defined as any smoking for 30 days or more at the time of
screening.
HDL-C <40 mg/dL (<1.0 mmol/L) at screening or TC/HDL-C ratio 6.
Family history of premature CHD (CHD in male first-degree relative <55 years; CHD
in female first-degree relative <65 years).
Age (men 55 years; women 65 years).
hs-CRP >2.0 mg/L at screening.
7. Lipids should meet the following criteria on a background treatment with a statin at the
2 screening visits:
a. Subjects with known CVD or CVD risk equivalents (Refer to 6a, above) at the highest
approved dose of statins described in 5, above:
Fasting LDL C 70 mg/dL (1.81 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Subjects not at the highest approved dose of statins described in 5, above:
Fasting LDL C 77 mg/dL (1.99 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
b. Subjects with multiple risk factors (Refer to 6b, above) at the highest approved dose of statins described in 5, above:
Fasting LDL C 100 mg/dL (2.59 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Subjects not at the highest approved dose of statins described in 5, above:
Fasting LDL C 110 mg/dL (2.85 mmol/L) at both screening visits and the value
at the second screening visit within 7 days of randomization 3 must not be lower
or higher than 20% of this initial value, as described in Section 7.1.
Fasting TG 400 mg/dL (4.51 mmol/L) at the second screening visit within 7 days of
randomization 3
.
8. Male and female subjects of childbearing potential must agree to use a highly effective
method of contraception throughout the study and for at least 63 days after the last dose
of assigned treatment. A subject is of childbearing potential if, in the opinion of the
investigator, he/she is biologically capable of having children and is sexually active
(Section 4.4.2).
Female subjects who are not of childbearing potential (ie, meet at least one of the
following criteria):
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure or;
Achieved post-menopausal status, defined as: cessation of regular menses for at
least 12 consecutive months with no alternative pathological or physiological
cause; and have a serum follicule-stimulating hormone(FSH) level within the
laboratory’s reference range for postmenopausal females.
Exclusion Criteria
Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of
the trial and their family members, site staff members otherwise supervised by the
Investigator, or subjects who are Pfizer employees directly involved in the conduct of the
trial.
2. Participation in other studies involving small molecule investigational drug(s)
(Phases 1-4) within 1 month except for cholesteryl ester transfer protein (CETP)
inhibitors (indefinitely), or biological agents within 6 months or 5 half lives, whichever is
longer before the current study begins and/or during study participation (the investigator
should refer to documents provided by the subject on the other study to determine the
investigational product half life). If the blind has been broken and the Investigator knows
(with documentation) that the subject received placebo, he/she can be included.
3. Subjects with prior exposure to PF-04950615 or other investigational PCSK9 inhibitor.
4. Subjects who are unable to receive injections, as either a self-injection, or administered
by a family member, health care assistant, or health care provider.
5. History of a cardiovascular or cerebrovascular event or procedure (eg, Myocardial
infarction, stroke, transient ischemic attack, angioplasty) during the past 30 days.
6. Congestive heart failure, New York Heart Association functional class IV, or Left
Ventricular Ejection Fraction measured by imaging <25%.
7. Poorly controlled hypertension at any screening visit or at randomization (defined as the
average of two systolic blood pressure measurements greater than 160 mm Hg or the
average of two diastolic blood pressure measurements greater than 100 mm Hg, even
with treatment). Subjects who have hypertension and are controlled on stable dosages of
anti hypertensive medications can be included. Subjects may be permitted into the study
if in the Principal Investigator’s opinion the assessment(s) are not clinically significant.
Blood pressure (BP) may be repeated up to three times within the hour or at the
completion of the office visit, to confirm a reading.
8. Any history of hemorrhagic stroke.
9. Any history of hypothyroidism or thyroid stimulating hormone (TSH) >1 X upper limit
of normal (ULN) at screening.
10. Current history of alcoholism or drug addiction according to the Diagnostic and
Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to
screening. Use of any recreational drugs within 12 months prior to screening.
11. History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell
cancer resolved by excision).
12. Medical history of positive testing for Human immunodeficiency virus (HIV).
13. Any disease or condition that might compromise the, hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless deemed not clinically significant by the Investigator and/or the Sponsor) or confound the interpretation of the study results. Examples of such conditions include but are not limited to nephrotic syndrome, uncontrolled diabetes, excessive alcohol consumption, cholestatic liver disease.
14. Use of statins other than atorvastatin, rosuvastatin or simvastatin.
15. Undergoing apheresis or have planned start of apheresis.
16. Initiation of, or change in, non lipid lowering prescription drugs, herbal medicine or supplements within 6 weeks of screening (exception: initiation or change in
multivitamins used for general health purposes are acceptable.)
17. Subjects on systemic corticosteroids at screening (ie, oral, intravenous (IV),
intramuscular (IM), or intra-articular. The use of corticosteroids by inhalation is
permitted.
18. Subjects taking prescription medications that are contraindicated with the use of statins at
screening. Refer to statin product labels for these medications.
19. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies (eg, Enbrel which contains the Fc portion of an antibody or Lucentis which is a Fab).
20. Subjects who are latex-sensitive (due to potential for exposure to latex or dry rubber in
the pre-filled syringe cap during self administration).
21. Any abnormal hematology values, clinical chemistries, urinalysis, or ECGs judged by the
Investigator as clinically significant which could impact on subject safety, were the
potential subject to be included in the study or interfere with interpretation of the study results.
22. Positive hepatitis B surface antigen (HBsAg), HB core antibody (HBcAb), or hepatitis C antibody tests indicative of present or prior infection. NOTE: If a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if the subject tests positive for antibody to HB surface antigen (HBsAb or anti HBs) reflex testing.
23. Creatinine kinase (CK) >3.0 X ULN at screening. A measurement >3.0 X ULN may be
repeated once during screening, and if <3.0 X ULN the subject is eligible.
24. Alanine transaminase (ALT) or aspartate transaminase (AST) >2 X ULN at screening.
25. Direct bilirubin >1.5 X ULN at screening.
26. GFR 4 <30 mL/min/1.73m2
or undergoing dialysis at screening.
27. Hemoglobin <12 g/dL (7.45 mmol/L) in men or <11 g/dL (6.83 mmol/L) in women.
28. Plans to donate blood during the study.
29. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
30. Pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 63 days after last dose of investigational product (Please refer to Contraception).
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of
the trial and their family members, site staff members otherwise supervised by the
Investigator, or subjects who are Pfizer employees directly involved in the conduct of the
trial.
2. Participation in other studies involving small molecule investigational drug(s)
(Phases 1-4) within 1 month except for cholesteryl ester transfer protein (CETP)
inhibitors (indefinitely), or biological agents within 6 months or 5 half lives, whichever is
longer before the current study begins and/or during study participation (the investigator
should refer to documents provided by the subject on the other study to determine the
investigational product half life). If the blind has been broken and the Investigator knows
(with documentation) that the subject received placebo, he/she can be included.
3. Subjects with prior exposure to PF-04950615 or other investigational PCSK9 inhibitor.
4. Subjects who are unable to receive injections, as either a self-injection, or administered
by a family member, health care assistant, or health care provider.
5. History of a cardiovascular or cerebrovascular event or procedure (eg, Myocardial
infarction, stroke, transient ischemic attack, angioplasty) during the past 30 days.
6. Congestive heart failure, New York Heart Association functional class IV, or Left
Ventricular Ejection Fraction measured by imaging <25%.
7. Poorly controlled hypertension at any screening visit or at randomization (defined as the
average of two systolic blood pressure measurements greater than 160 mm Hg or the
average of two diastolic blood pressure measurements greater than 100 mm Hg, even
with treatment). Subjects who have hypertension and are controlled on stable dosages of
anti hypertensive medications can be included. Subjects may be permitted into the study
if in the Principal Investigator’s opinion the assessment(s) are not clinically significant.
Blood pressure (BP) may be repeated up to three times within the hour or at the
completion of the office visit, to confirm a reading.
8. Any history of hemorrhagic stroke.
9. Any history of hypothyroidism or thyroid stimulating hormone (TSH) >1 X upper limit
of normal (ULN) at screening.
10. Current history of alcoholism or drug addiction according to the Diagnostic and
Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to
screening. Use of any recreational drugs within 12 months prior to screening.
11. History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell
cancer resolved by excision).
12. Medical history of positive testing for Human immunodeficiency virus (HIV).
13. Any disease or condition that might compromise the, hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless deemed not clinically significant by the Investigator and/or the Sponsor) or confound the interpretation of the study results. Examples of such conditions include but are not limited to nephrotic syndrome, uncontrolled diabetes, excessive alcohol consumption, cholestatic liver disease.
14. Use of statins other than atorvastatin, rosuvastatin or simvastatin.
15. Undergoing apheresis or have planned start of apheresis.
16. Initiation of, or change in, non lipid lowering prescription drugs, herbal medicine or supplements within 6 weeks of screening (exception: initiation or change in
multivitamins used for general health purposes are acceptable.)
17. Subjects on systemic corticosteroids at screening (ie, oral, intravenous (IV),
intramuscular (IM), or intra-articular. The use of corticosteroids by inhalation is
permitted.
18. Subjects taking prescription medications that are contraindicated with the use of statins at
screening. Refer to statin product labels for these medications.
19. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies (eg, Enbrel which contains the Fc portion of an antibody or Lucentis which is a Fab).
20. Subjects who are latex-sensitive (due to potential for exposure to latex or dry rubber in
the pre-filled syringe cap during self administration).
21. Any abnormal hematology values, clinical chemistries, urinalysis, or ECGs judged by the
Investigator as clinically significant which could impact on subject safety, were the
potential subject to be included in the study or interfere with interpretation of the study results.
22. Positive hepatitis B surface antigen (HBsAg), HB core antibody (HBcAb), or hepatitis C antibody tests indicative of present or prior infection. NOTE: If a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if the subject tests positive for antibody to HB surface antigen (HBsAb or anti HBs) reflex testing.
23. Creatinine kinase (CK) >3.0 X ULN at screening. A measurement >3.0 X ULN may be
repeated once during screening, and if <3.0 X ULN the subject is eligible.
24. Alanine transaminase (ALT) or aspartate transaminase (AST) >2 X ULN at screening.
25. Direct bilirubin >1.5 X ULN at screening.
26. GFR 4 <30 mL/min/1.73m2
or undergoing dialysis at screening.
27. Hemoglobin <12 g/dL (7.45 mmol/L) in men or <11 g/dL (6.83 mmol/L) in women.
28. Plans to donate blood during the study.
29. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
30. Pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 63 days after last dose of investigational product (Please refer to Contraception).
The Estimated Number of Participants
-
Taiwan
38 participants
-
Global
1600 participants
