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

NCT01979601 | Completed Phase 1

• 1 other identifier: CLGT209X2101
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

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

Conditions

Hypercholesterolemia

Keywords

hypercholesterolemia,; LGT209,; PCSK9,; LDL-C

Outcome Measures

Primary Outcomes (8)

• Number of patients with adverse events, serious adverse events and death

  from Screening until Day 141

• 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

• 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

• 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

• 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 Outcomes (10)

• 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

• Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients

  Baseline, Day 29

• 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

• 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

Study Arms (12)

Patient: LGT209 0.3 mg/kg

EXPERIMENTAL

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

Drug: LGT209

Patient: LGT209 1 mg/kg

EXPERIMENTAL

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

Drug: LGT209

Patient: LGT209 3 mg/kg

EXPERIMENTAL

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

Drug: LGT209

Patient: LGT209 10 mg/kg

EXPERIMENTAL

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

Drug: LGT209

Patient: LGT209 20 mg/kg

EXPERIMENTAL

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

Drug: LGT209

Healthy Volunteers: LGT209 0.3 mg/kg

EXPERIMENTAL

0.3 mg/kg LGT209 intravenous administration in healthy volunteers

Drug: LGT209

Healthy Volunteers: LGT209 1 mg/kg

EXPERIMENTAL

1 mg/kg LGT209 intravenous administration in healthy volunteers

Drug: LGT209

Healthy Volunteers: LGT209 3 mg/kg

EXPERIMENTAL

3 mg/kg LGT209 intravenous administration in healthy volunteers

Drug: LGT209

Healthy Volunteers: LGT209 10 mg/kg

EXPERIMENTAL

10 mg/kg LGT209 intravenous administration in healthy volunteers

Drug: LGT209

Healthy Volunteers: 20 mg/kg

EXPERIMENTAL

20 mg/kg LGT209 intravenous administration in healthy volunteers

Drug: LGT209

Patient: Placebo

PLACEBO COMPARATOR

Matching intravenous placebo in patients on stable doses of statins

Drug: Placebo

Healthy Volunteers: Placebo

PLACEBO COMPARATOR

Matching intravenous placebo in healthy volunteers

Drug: Placebo

Interventions

LGT209 DRUG

150 mg lyophilized powder in glass vial

Healthy Volunteers: 20 mg/kg; Healthy Volunteers: LGT209 0.3 mg/kg; Healthy Volunteers: LGT209 1 mg/kg; Healthy Volunteers: LGT209 10 mg/kg; Healthy Volunteers: LGT209 3 mg/kg; Patient: LGT209 0.3 mg/kg; Patient: LGT209 1 mg/kg; Patient: LGT209 10 mg/kg; Patient: LGT209 20 mg/kg; Patient: LGT209 3 mg/kg

Placebo DRUG

Placebo comparator

Healthy Volunteers: Placebo; Patient: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Miami Gardens, Florida, 33169, United States

Location

Novartis Investigative Site

Fargo, North Dakota, 58104, United States

Location

MeSH Terms

Conditions

Hypercholesterolemia; Hypercholesterolemia, Autosomal Dominant, 3

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: November 8, 2013
• Study Start: December 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

US (2)