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Safety, Tolerability, PK and PD of LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia

Primary Purpose

Hypercholesterolemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LGT209
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring hypercholesterolemia,, LGT209,, PCSK9,, LDL-C

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy volunteers: Male and female subjects 18 to 70 years of age, in general good health but with high cholesterol
  • Statin patients: Male and female patients 18 to 70 years of age, with high cholesterol on stable statin therapy for at least 3 months

Exclusion Criteria:

  • Healthy volunteers: History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
  • Women of child-bearing potential unless using highly effective methods of contraception
  • Statin patients: Use of any prescription drugs for lipid lowering other than HMG CO-A reductase inhibitors (statins); use of two concurrent antihypertensive medications is allowed, provided stable dosing has been achieved for the prior 3 months
  • Women of child-bearing potential unless using highly effective methods of contraception

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Patient: LGT209 0.3 mg/kg

Patient: LGT209 1 mg/kg

Patient: LGT209 3 mg/kg

Patient: LGT209 10 mg/kg

Patient: LGT209 20 mg/kg

Healthy Volunteers: LGT209 0.3 mg/kg

Healthy Volunteers: LGT209 1 mg/kg

Healthy Volunteers: LGT209 3 mg/kg

Healthy Volunteers: LGT209 10 mg/kg

Healthy Volunteers: 20 mg/kg

Patient: Placebo

Healthy Volunteers: Placebo

Arm Description

0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins

1 mg/kg LGT209 intravenous administration in patients on stable doses of statins

3 mg/kg LGT209 intravenous administration in patients on stable doses of statins

10 mg/kg LGT209 intravenous administration in patients on stable doses of statins

20 mg/kg LGT209 intravenous administration in patients on stable doses of statins

0.3 mg/kg LGT209 intravenous administration in healthy volunteers

1 mg/kg LGT209 intravenous administration in healthy volunteers

3 mg/kg LGT209 intravenous administration in healthy volunteers

10 mg/kg LGT209 intravenous administration in healthy volunteers

20 mg/kg LGT209 intravenous administration in healthy volunteers

Matching intravenous placebo in patients on stable doses of statins

Matching intravenous placebo in healthy volunteers

Outcomes

Primary Outcome Measures

Number of patients with adverse events, serious adverse events and death
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy volunteers
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Pharmacokinetics of LGT209: : Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: observed maximum serum concentrations (Cmax) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve (T1/2) of LGT209 in patients and healthy volunteers following intravenous administration
Number of healthy volunteers with adverse events, serious adverse events and death

Secondary Outcome Measures

Pharmacokinetics of intravenous LGT209 in relationship to concentrations of PCSK9 and LDL-C in patients and healthy volunteers
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to time 't' (AUC0-t)
In AUC 0-t, t is a defined as time point after administration of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Dose-normalized area under the serum concentration-time curve (AUC/D) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Dose-normalized maximum serum concentrations (Cmax/D) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Volume of distribution during the terminal elimination phase (Vz) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Volume of distribution at steady state (Vss) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: Mean residence time (MRT) of LGT209 in patients and healthy volunteers following intravenous administration
Pharmacokinetics of LGT209: the systemic (or total body) clearance from serum following intravenous administration

Full Information

First Posted
November 4, 2013
Last Updated
December 9, 2013
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01979601
Brief Title
Safety, Tolerability, PK and PD of LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia
Official Title
A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenously Administered LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia on Stable Doses of Statin Medications
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
This study is designed to measure the effects of LGT209 when given intravenously to patients with high cholesterol who are on stable doses of statin medications, and to healthy subjects with elevated cholesterol

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
Keywords
hypercholesterolemia,, LGT209,, PCSK9,, LDL-C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patient: LGT209 0.3 mg/kg
Arm Type
Experimental
Arm Description
0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Arm Title
Patient: LGT209 1 mg/kg
Arm Type
Experimental
Arm Description
1 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Arm Title
Patient: LGT209 3 mg/kg
Arm Type
Experimental
Arm Description
3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Arm Title
Patient: LGT209 10 mg/kg
Arm Type
Experimental
Arm Description
10 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Arm Title
Patient: LGT209 20 mg/kg
Arm Type
Experimental
Arm Description
20 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Arm Title
Healthy Volunteers: LGT209 0.3 mg/kg
Arm Type
Experimental
Arm Description
0.3 mg/kg LGT209 intravenous administration in healthy volunteers
Arm Title
Healthy Volunteers: LGT209 1 mg/kg
Arm Type
Experimental
Arm Description
1 mg/kg LGT209 intravenous administration in healthy volunteers
Arm Title
Healthy Volunteers: LGT209 3 mg/kg
Arm Type
Experimental
Arm Description
3 mg/kg LGT209 intravenous administration in healthy volunteers
Arm Title
Healthy Volunteers: LGT209 10 mg/kg
Arm Type
Experimental
Arm Description
10 mg/kg LGT209 intravenous administration in healthy volunteers
Arm Title
Healthy Volunteers: 20 mg/kg
Arm Type
Experimental
Arm Description
20 mg/kg LGT209 intravenous administration in healthy volunteers
Arm Title
Patient: Placebo
Arm Type
Placebo Comparator
Arm Description
Matching intravenous placebo in patients on stable doses of statins
Arm Title
Healthy Volunteers: Placebo
Arm Type
Placebo Comparator
Arm Description
Matching intravenous placebo in healthy volunteers
Intervention Type
Drug
Intervention Name(s)
LGT209
Intervention Description
150 mg lyophilized powder in glass vial
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator
Primary Outcome Measure Information:
Title
Number of patients with adverse events, serious adverse events and death
Time Frame
from Screening until Day 141
Title
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers
Description
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Time Frame
Baseline, Day 29
Title
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy volunteers
Description
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Time Frame
Baseline, Day 29
Title
Pharmacokinetics of LGT209: : Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2); 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: observed maximum serum concentrations (Cmax) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve (T1/2) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Number of healthy volunteers with adverse events, serious adverse events and death
Time Frame
from Screening until Day 141
Secondary Outcome Measure Information:
Title
Pharmacokinetics of intravenous LGT209 in relationship to concentrations of PCSK9 and LDL-C in patients and healthy volunteers
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients
Description
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Time Frame
Baseline, Day 29
Title
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients
Description
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Time Frame
Baseline, Day 29
Title
Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to time 't' (AUC0-t)
Description
In AUC 0-t, t is a defined as time point after administration of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Dose-normalized area under the serum concentration-time curve (AUC/D) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Dose-normalized maximum serum concentrations (Cmax/D) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 ( 1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Volume of distribution during the terminal elimination phase (Vz) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Volume of distribution at steady state (Vss) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: Mean residence time (MRT) of LGT209 in patients and healthy volunteers following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Title
Pharmacokinetics of LGT209: the systemic (or total body) clearance from serum following intravenous administration
Time Frame
Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy volunteers: Male and female subjects 18 to 70 years of age, in general good health but with high cholesterol Statin patients: Male and female patients 18 to 70 years of age, with high cholesterol on stable statin therapy for at least 3 months Exclusion Criteria: Healthy volunteers: History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes Women of child-bearing potential unless using highly effective methods of contraception Statin patients: Use of any prescription drugs for lipid lowering other than HMG CO-A reductase inhibitors (statins); use of two concurrent antihypertensive medications is allowed, provided stable dosing has been achieved for the prior 3 months Women of child-bearing potential unless using highly effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Miami Gardens
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
Novartis Investigative Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58104
Country
United States

12. IPD Sharing Statement

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Safety, Tolerability, PK and PD of LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia

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