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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
  Purpose

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


Condition Intervention Phase
Hypercholesterolemia
Drug: LGT209
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 74
Study Start Date: December 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patient: LGT209 0.3 mg/kg
0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Patient: LGT209 1 mg/kg
1 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Patient: LGT209 3 mg/kg
3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Patient: LGT209 10 mg/kg
10 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Patient: LGT209 20 mg/kg
20 mg/kg LGT209 intravenous administration in patients on stable doses of statins
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Healthy Volunteers: LGT209 0.3 mg/kg
0.3 mg/kg LGT209 intravenous administration in healthy volunteers
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Healthy Volunteers: LGT209 1 mg/kg
1 mg/kg LGT209 intravenous administration in healthy volunteers
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Healthy Volunteers: LGT209 3 mg/kg
3 mg/kg LGT209 intravenous administration in healthy volunteers
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Healthy Volunteers: LGT209 10 mg/kg
10 mg/kg LGT209 intravenous administration in healthy volunteers
Drug: LGT209
150 mg lyophilized powder in glass vial
Experimental: Healthy Volunteers: 20 mg/kg
20 mg/kg LGT209 intravenous administration in healthy volunteers
Drug: LGT209
150 mg lyophilized powder in glass vial
Placebo Comparator: Patient: Placebo
Matching intravenous placebo in patients on stable doses of statins
Drug: Placebo
Placebo comparator
Placebo Comparator: Healthy Volunteers: Placebo
Matching intravenous placebo in healthy volunteers
Drug: Placebo
Placebo comparator

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01979601

Locations
United States, Florida
Novartis Investigative Site
Miami Gardens, Florida, United States, 33169
United States, North Dakota
Novartis Investigative Site
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01979601     History of Changes
Other Study ID Numbers: CLGT209X2101
Study First Received: November 4, 2013
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
hypercholesterolemia,
LGT209,
PCSK9,
LDL-C

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 25, 2014