Safety, Tolerability, PK and PD of LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia
- Registration Number
- NCT01979601
- Lead Sponsor
- Novartis Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Patient: LGT209 1 mg/kg LGT209 1 mg/kg LGT209 intravenous administration in patients on stable doses of statins Patient: LGT209 3 mg/kg LGT209 3 mg/kg LGT209 intravenous administration in patients on stable doses of statins Patient: LGT209 10 mg/kg LGT209 10 mg/kg LGT209 intravenous administration in patients on stable doses of statins Patient: LGT209 0.3 mg/kg LGT209 0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins Healthy Volunteers: LGT209 1 mg/kg LGT209 1 mg/kg LGT209 intravenous administration in healthy volunteers Healthy Volunteers: LGT209 3 mg/kg LGT209 3 mg/kg LGT209 intravenous administration in healthy volunteers Healthy Volunteers: LGT209 10 mg/kg LGT209 10 mg/kg LGT209 intravenous administration in healthy volunteers Healthy Volunteers: 20 mg/kg LGT209 20 mg/kg LGT209 intravenous administration in healthy volunteers Patient: Placebo Placebo Matching intravenous placebo in patients on stable doses of statins Healthy Volunteers: Placebo Placebo Matching intravenous placebo in healthy volunteers Patient: LGT209 20 mg/kg LGT209 20 mg/kg LGT209 intravenous administration in patients on stable doses of statins Healthy Volunteers: LGT209 0.3 mg/kg LGT209 0.3 mg/kg LGT209 intravenous administration in healthy volunteers
- Primary Outcome Measures
Name Time Method Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers Baseline, Day 29 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, Day 29 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 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 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 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 Number of patients with adverse events, serious adverse events and death from Screening until Day 141 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 Number of healthy volunteers with adverse events, serious adverse events and death from Screening until Day 141
- Secondary Outcome Measures
Name Time Method 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 Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients Baseline, Day 29 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, Day 29 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: 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 Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to time 't' (AUC0-t) 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 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 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 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 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 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 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
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸Fargo, North Dakota, United States