Multiple-Dose Safety Study Of RN316 For TheTreatment Of Hypercholesterolemia

A Phase 1, Placebo-Controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Multiple Intravenous Doses Of RN316 In Healthy Adult Subjects With Hypercholesterolemia

The primary objective of this study is to evaluate the safety and tolerability of repeated doses of RN316 in eligible healthy volunteers. RN316 is an investigational drug that is currently being studied as a cholesterol lowering therapy.

Study Overview

• Status: Withdrawn
• Conditions: Dyslipidemia; Hypercholesterolemia
• Intervention / Treatment: Biological: Placebo; Biological: 1 mg/kg every 2 weeks; Biological: 2 mg/kg every 4 weeks; Biological: 4 mg/kg every 4 weeks; Biological: 4 mg/kg every 8 weeks; Biological: 8 mg/kg every 8 weeks; Biological: 12 mg/kg every 8 weeks

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• LDL-C must be greater or equal to 130 mg/dl
• BMI must be between 18.5 and 40 kg/m2

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 1 mg/kg every 2 weeks	Biological: 1 mg/kg every 2 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 2 mg/kg every 4 weeks	Biological: 2 mg/kg every 4 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 4 mg/kg every 4 weeks	Biological: 4 mg/kg every 4 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 4 mg/kg every 8 weeks	Biological: 4 mg/kg every 8 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 8 mg/kg every 8 weeks	Biological: 8 mg/kg every 8 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.
Experimental: RN316: 12 mg/kg every 8 weeks	Biological: 12 mg/kg every 8 weeks; Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting or intolerable treatment related adverse events (AEs).	Every Scheduled Visit
Incidence, severity and causal relationship of treatment emergent AEs (TEAEs).	Every Scheduled Visit
Incidence of abnormal and clinically relevant safety laboratories.	Screening and Days 29, 57, 85, 113, 135, 141, 169 and 197
Abnormal and clinically relevant changes in vital signs, BP, and ECG parameters.	Every Scheduled Visit
Incidence of anti-drug-antibodies.	Baseline and Day 15 and monthly thereafter

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameter estimates including but not be limited to: AUC, Tmax, Cmax terminal elimination half life (t1/2), Clearance (CL), volume of distribution at steady state (Vss), and accumulation ratio (R) of RN316.	Day 1 and every scheduled visit thereafter
Absolute and percentage change in LDL C from baseline.	Every scheduled visit except Day 1
Proportion of subjects who achieve a target LDL C of <100 mg/mL.	Every scheduled visit except Day 1
Proportion of subjects who achieve a target LDL C of <70 mg/dL.	Every scheduled visit except Day 1
Proportion of subjects achieving 50% decrease in LDL C from baseline.	Every scheduled visit except Day 1

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): March 1, 2011
• Study Completion (Anticipated): March 1, 2011

Study Registration Dates

• First Submitted: July 14, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Estimate): April 23, 2015
• Last Update Submitted That Met QC Criteria: April 21, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Cholesterol; Dyslipidemia; Hypercholesterolemia; High Cholesterol; LDL
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: B1481002