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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01979601
• Other study ID #: CLGT209X2101
• Status: Completed
• Phase: Phase 1
• First received: November 4, 2013
• Last updated: December 9, 2013
• Start date: December 2010
• Est. completion date: November 2011

Study information

• Verified date: December 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• LGT209
150 mg lyophilized powder in glass vial
• Placebo
Placebo comparator

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Fargo	North Dakota
United States	Novartis Investigative Site	Miami Gardens	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events, serious adverse events and death		from Screening until Day 141	Yes
Primary	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)	Baseline, Day 29	No
Primary	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)	Baseline, Day 29	No
Primary	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		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	No
Primary	Pharmacokinetics of LGT209: observed maximum serum concentrations (Cmax) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Primary	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		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	No
Primary	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		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	No
Primary	Number of healthy volunteers with adverse events, serious adverse events and death		from Screening until Day 141	Yes
Secondary	Pharmacokinetics of intravenous LGT209 in relationship to concentrations of PCSK9 and LDL-C in patients and healthy volunteers		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	No
Secondary	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)	Baseline, Day 29	No
Secondary	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)	Baseline, Day 29	No
Secondary	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	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	No
Secondary	Pharmacokinetics of LGT209: Dose-normalized area under the serum concentration-time curve (AUC/D) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Secondary	Pharmacokinetics of LGT209: Dose-normalized maximum serum concentrations (Cmax/D) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Secondary	Pharmacokinetics of LGT209: Volume of distribution during the terminal elimination phase (Vz) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Secondary	Pharmacokinetics of LGT209: Volume of distribution at steady state (Vss) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Secondary	Pharmacokinetics of LGT209: Mean residence time (MRT) of LGT209 in patients and healthy volunteers following intravenous administration		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	No
Secondary	Pharmacokinetics of LGT209: the systemic (or total body) clearance from serum following intravenous administration		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	No