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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01979601
First received: November 4, 2013
Last updated: December 9, 2013
Last verified: December 2013

November 4, 2013
December 9, 2013
December 2010
November 2011   (final data collection date for primary outcome measure)
  • Number of patients with adverse events, serious adverse events and death [ Time Frame: from Screening until Day 141 ] [ Designated as safety issue: Yes ]
  • Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of healthy volunteers with adverse events, serious adverse events and death [ Time Frame: from Screening until Day 141 ] [ Designated as safety issue: Yes ]
  • Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
  • Chnage from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy volunteers [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of subjects (patients and healthy volunteers) with adverse events, serious adverse events and death [ Time Frame: from Screening until Day 141 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01979601 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
  • Chnage from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety, Tolerability, PK and PD of LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia
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

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: LGT209
    150 mg lyophilized powder in glass vial
  • Drug: Placebo
    Placebo comparator
  • Experimental: Patient: LGT209 0.3 mg/kg
    0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
    Intervention: Drug: LGT209
  • Experimental: Patient: LGT209 1 mg/kg
    1 mg/kg LGT209 intravenous administration in patients on stable doses of statins
    Intervention: Drug: LGT209
  • Experimental: Patient: LGT209 3 mg/kg
    3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
    Intervention: Drug: LGT209
  • Experimental: Patient: LGT209 10 mg/kg
    10 mg/kg LGT209 intravenous administration in patients on stable doses of statins
    Intervention: Drug: LGT209
  • Experimental: Patient: LGT209 20 mg/kg
    20 mg/kg LGT209 intravenous administration in patients on stable doses of statins
    Intervention: Drug: LGT209
  • Experimental: Healthy Volunteers: LGT209 0.3 mg/kg
    0.3 mg/kg LGT209 intravenous administration in healthy volunteers
    Intervention: Drug: LGT209
  • Experimental: Healthy Volunteers: LGT209 1 mg/kg
    1 mg/kg LGT209 intravenous administration in healthy volunteers
    Intervention: Drug: LGT209
  • Experimental: Healthy Volunteers: LGT209 3 mg/kg
    3 mg/kg LGT209 intravenous administration in healthy volunteers
    Intervention: Drug: LGT209
  • Experimental: Healthy Volunteers: LGT209 10 mg/kg
    10 mg/kg LGT209 intravenous administration in healthy volunteers
    Intervention: Drug: LGT209
  • Experimental: Healthy Volunteers: 20 mg/kg
    20 mg/kg LGT209 intravenous administration in healthy volunteers
    Intervention: Drug: LGT209
  • Placebo Comparator: Patient: Placebo
    Matching intravenous placebo in patients on stable doses of statins
    Intervention: Drug: Placebo
  • Placebo Comparator: Healthy Volunteers: Placebo
    Matching intravenous placebo in healthy volunteers
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
74
November 2011
November 2011   (final data collection date for primary outcome measure)

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

Both
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01979601
CLGT209X2101
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP