Safety And Tolerability Of Multiple Doses Of PF-04950615 (RN316) In Subjects With Hypercholesterolemia

Hypercholesterolemia Clinical Trial

Official title:

A Phase 1, Placebo-controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Multiple Intravenous Doses Of Pf-04950615 In Healthy Adult Subjects With Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01243151
• Other study ID #: B1481009
• Status: Completed
• Phase: Phase 1
• Start date: February 2011
• Est. completion date: October 2011

Study information

• Verified date: August 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the safety and tolerability of repeated doses of PF-04950615 (RN316) in study volunteers with hypercholesterolemia. PF-04950615 is an investigational drug that is currently being studied as a lipid lowering agent.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• LDL-C must be greater or equal to 130 mg/dl

• BMI must be between 18.5 and 40 kg/m2

• Japanese volunteers must have 4 Japanese grand parents born in Japan

Exclusion Criteria:

• History of cardiovascular or cerebrovascular event during the past year.

• Poorly controlled type 1 or type 2 diabetes mellitus

• Subjects who have taken lipid lowering therapies within the last 3 months of screening.

Related Conditions & MeSH terms

• Dyslipidemia
• Dyslipidemias
• Hypercholesterolemia

Intervention

Biological:
• PF-04950615 (RN316)
Infusion every week
• PF-04950615 (RN316)
Infusion every week
• PF-04950615 (RN316)
Infusion every week
• PF-04950615 (RN316)
Infusion every week
• PF-04950615 (RN316)
Infusion every week

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group	Culver City	California
United States	Glendale Adventist Medical Center	Glendale	California
United States	Covance Clinical Research Unit, Inc.	Honolulu	Hawaii
United States	SeaView Research, Inc.	Miami	Florida
United States	SeaView Research, Inc.	Miami	Florida
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	Prism Research	Saint Paul	Minnesota
United States	Healthcare Discoveries, LLC dba ICON Development Solutions	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting and Intolerable Treatment-Related Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Dose limiting and intolerable treatment-related AEs were the AEs resulting from drug overdose, drug withdrawal, drug abuse, drug misuse, drug interactions, drug dependency, extravasation, exposure in utero, exposure during breast feeding.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-Related Adverse Events (AEs)	An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to Day 78 that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Adverse Events (AEs) by Severity	An AE was any untoward medical occurrence in a participant who received study drug. AE was assessed according to common terminology criteria for adverse events (CTCAE) version 4.0 severity grades- Grade 1: mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2: moderate (minimal, local or non invasive intervention indicated); Grade 3: severe (medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling); Grade 4: Life-threatening consequences; urgent intervention indicated and Grade 5: Death related to AE.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Laboratory Test Abnormalities	Criteria: Haemoglobin(Hgb), hematocrit, RBC: <0.8*lower limit of normal(LLN),mean corpuscular volume, mean corpuscular Hgb concentration <0.9*LLN or>1.1*upper limit of normal(ULN), platelet<0.5*LLN or>1.75*ULN, WBC<0.6*LLN or>1.5*ULN, lymphocyte, neutrophil<0.8*LLN or>1.2*ULN, basophil, eosinophil, monocyte>1.2*ULN; bilirubin>1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase>3.0*ULN,total protein,albumin<0.8*LLN or>1.2*ULN; blood urea nitrogen, creatinine>1.3*ULN,uric acid>1.2*ULN;sodium<0.95*LLNor>1.05*ULN,potassium,chloride,calcium,bicarbonate<0.9*LLN or>1.1*ULN; glucose<0.6*LLN or >1.5*ULN, urine specific gravity<1.003 or>1.030,urine pH<4.5or>8,urine glucose, ketones, urine protein,urine blood/Hgb,urobilinogen,bilirubin,nitrite, leukocyte esterase>=1; urine RBC,WBC>=20,urine epithelial cells>=6,urine granular casts,hyaline casts>1,urine bacteria>20,partial thromboplastin time,prothrombin:>1.1*ULN.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Clinically Relevant Changes in Vital Signs	Criteria for clinically relevant vital signs: supine and standing systolic blood pressure (SBP): less than (<) 90 millimeter of mercury (mmHg); supine and standing diastolic blood pressure (DBP): <50 mmHg. Maximum increase from baseline (IFB) or decrease from baseline (DFB) in supine and standing SBP: greater than or equal to (>=) 30 mmHg and maximum IFB or DFB in supine and standing DBP: >=20 mmHg. Supine pulse rate: <40 and greater than (>) 120 beats per minute (bpm); standing pulse rate: <40 and >140 bpm.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Parameters	Criteria for clinically relevant ECG parameters: PR interval: maximum IFB of >=25 percent or 50 percent; QRS complex: maximum IFB of >=25 or 50 percent; QTcF interval (Fridericia's Correction): maximum IFB of >=30 millisecond (msec) to <60 msec and maximum IFB of >=60 msec.	Baseline up to Follow-up period (Day 78)
Primary	Number of Participants With Anti-drug Antibodies (ADA)	The number of participants with at least one positive ADA were summarized for each treatment arm. Participants with positive antibody titer of >4.32 milligram/milliliter (mg/mL) were considered as ADA positive.	Baseline up to Follow-up period (Day 78)
Secondary	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615	AUCtau is area under the concentration-time profile from time zero to time tau (t), the dosing interval, where tau =168 hours.	Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615	Tmax is the time at which maximum plasma concentration (Cmax) occurred.	Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-04950615		Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Plasma Decay Half-Life (t1/2) of PF-04950615	t1/2 was the time measured for the plasma concentration of PF-04950615 to decrease by one half. t1/2 was calculated as Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Day 1 and 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Apparent Clearance (CL) of PF-04950615	CL was calculated as Dose/AUCtau. AUCtau is area under the concentration-time profile from time zero to time tau, the dosing interval, where tau=168 hours.	Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Volume of Distribution at Steady State (Vss) of PF-04950615	Vss was calculated as CL*MRT. CL was calculated as Dose/AUCtau, where AUCtau was area under the concentration-time profile from time zero to time tau (t), the dosing interval, where tau=168 hours. MRT was mean residence time (predicted) extrapolated to infinity.	Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Accumulation Ratio (Rac) of PF-04950615	Rac was calculated as Day 22 AUCtau divided by Day 1 AUCtau, where AUCtau is area under the concentration-time profile from time zero to time tau (t), the dosing interval, where tau =168 hours.	Day 22: pre-dose and 1, 6, 9, 24 and 72 hours post dose
Secondary	Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Number of Participants Achieving LDL-C Less Than (<) 70 Milligram Per Deciliter (mg/dL)		Day 15, 22, 29 and 36
Secondary	Number of Participants Achieving LDL-C Less Than (<) 100 Milligram Per Deciliter (mg/dL)		Day 15, 22, 29 and 36
Secondary	Number of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in LDL-C From Baseline		Baseline, Day 15, 22, 29 and 36
Secondary	Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline in Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline in Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline in Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78		Baseline, Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline in Lipid Parameters: Apolipoprotein A1 (ApoA1) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline In Lipid Parameters: Apolipoprotein B (ApoB) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline In Lipid Parameters: Total Cholesterol at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline In Lipid Parameters: High Density Lipoprotein Cholesterol (HDL-C) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline In Lipid Parameters: Non High Density Lipoprotein Cholesterol (Non HDL-C) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Percent Change From Baseline In Lipid Parameters: Triglycerides (TG) at Day 8, 15, 22, 29 and 78		Day 8, 15, 22, 29 and 78
Secondary	Change From Baseline In Low Density Lipoprotein Cholesterol (LDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Change From Baseline In Small Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Change From Baseline In Medium Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Change From Baseline In Large Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Change From Baseline In Total Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Levels at Baseline, Day 8, 15, 22, 36, 50, 64 and 78		Baseline, Day 8, 15, 22, 36, 50, 64 and 78
Secondary	C-Reactive Protein Levels at Day 8, 15, 21, 36, 57 and 78		Day 8, 15, 21, 36, 57 and 78
Secondary	Small High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Medium High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Large High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Total High Density Lipoprotein-Cholesterol (HDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Small Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Medium Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Large Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Total Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Levels at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	High Density Lipoprotein-Cholesterol (HDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78
Secondary	Very Low Density Lipoprotein-Cholesterol (VLDL-C) Particle Size at Day 8, 15, 22, 36, 50, 64 and 78		Day 8, 15, 22, 36, 50, 64 and 78

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