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Dose-ranging Efficacy and Pharmacokinetics Study of Intravenous Atorvastatin in Hypercholesterolemic Patients

Phase 2
Completed
Conditions
Hypercholesterolemia
Dyslipidemias
Interventions
Registration Number
NCT03611010
Lead Sponsor
Cumberland Pharmaceuticals
Brief Summary

Open-label study will titrate doses of intravenous atorvastatin and monitor respective LDL-C levels in hypercholesterolemic patients previously controlled on oral atorvastatin.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • On stable dose of daily oral atorvastatin for >= 5 weeks (oral atorvastatin may be provided during a lead-in period for subjects not previously taking atorvastatin)
  • Stable LDL-C confirmed in the previous 7 to 10 days prior to enrollment into the treatment phase.
Exclusion Criteria
  • History of myopathy or rhabdomyolysis
  • Liver disease including current biliary disorders
  • Positive for HIV, Hepatitis B or Hepatitis C Virus
  • Abuse of alcohol or non-prescribed drugs
  • Unstable angina or arrhythmias or a cardiac event in the previous three months
  • hypothyroidism, diabetes, or hypertension that is not under control
  • pregnant or plans to be pregnant

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort 4Atorvastatin injectionCohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days
Cohort 1Atorvastatin injectionCohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 2Atorvastatin injectionCohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 3Atorvastatin injectionCohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Primary Outcome Measures
NameTimeMethod
Efficacy, Number of Participants With Day 15 LDL-C Less Than or Equal to 125% of Baseline LDL-CBaseline, 15 Days

LDL-C levels were measured prior to and at the end of the 15 day treatment period to quantify the percent baseline LDL-C at 15 days. Efficacy is defined as eleven or more subjects in a dosing cohort with a Day 15 LDL-C not more than 125% of their baseline.

Secondary Outcome Measures
NameTimeMethod
Tmax IV3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The time to maximum concentration of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.

AUC 0-243 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The AUC 0-24 of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.

AUC Inf3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The AUCinf of atorvastatin following an intravenous injection to a patient at steady-state.

VDss3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The volume of distribution at steady state of atorvastatin following an intravenous injection to a patient.

t 1/23 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The half-life of atorvastatin following an intravenous injection to a patient at a steady state.

Change in Baseline LDL-C ConcentrationBaseline, 15 days

Mean change in LDL-C (mg/dL) from baseline at Day 15

Cmax IV3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

The maximum serum concentration of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.

Efficacy, Number of Participants With Day 15 HDL-C More Than or Equal to 75% Baseline HDL-CBaseline, 15 Days

HDL-C levels were measured prior to and at the end of the 15 day treatment period to quantify the percent baseline HDL-C at 15 days. Efficacy is defined as eleven or more subjects in a dosing cohort with a Day 15 HDL-C not less than 75% of their baseline.

Trial Locations

Locations (1)

Frontage Clinical Services

🇺🇸

Secaucus, New Jersey, United States

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