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

Phase II, Dose-ranging Study to Evaluate the Efficacy Dose Response and Pharmacokinetics of Intravenous Atorvastatin in Hypercholesterolemic Patients Previously Controlled With Oral Atorvastatin

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

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hypercholesterolemia
• Intervention / Treatment: Drug: Atorvastatin injection

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days	Drug: Atorvastatin injection; statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
EXPERIMENTAL: Cohort 2; Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days	Drug: Atorvastatin injection; statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
EXPERIMENTAL: Cohort 3; Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days	Drug: Atorvastatin injection; statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
EXPERIMENTAL: Cohort 4; Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days	Drug: Atorvastatin injection; statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy, Number of Participants With Day 15 LDL-C Less Than or Equal to 125% of Baseline LDL-C	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.	Baseline, 15 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy, Number of Participants With Day 15 HDL-C More Than or Equal to 75% Baseline HDL-C	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.	Baseline, 15 Days
Change in Baseline LDL-C Concentration	Mean change in LDL-C (mg/dL) from baseline at Day 15	Baseline, 15 days
Cmax IV	The maximum serum concentration of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Tmax IV	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.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
AUC 0-24	The AUC 0-24 of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
AUC Inf	The AUCinf of atorvastatin following an intravenous injection to a patient at steady-state.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
VDss	The volume of distribution at steady state of atorvastatin following an intravenous injection to a patient.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
t 1/2	The half-life of atorvastatin following an intravenous injection to a patient at a steady state.	3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Gregory Tracey, MD, Frontage Lab

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 7, 2018
• Primary Completion (ACTUAL): February 17, 2020
• Study Completion (ACTUAL): February 24, 2020

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (ACTUAL): August 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: CPI-1103-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No