Back to resultsDose-ranging Efficacy and Pharmacokinetics Study of Intravenous Atorvastatin in Hypercholesterolemic Patients
Primary Purpose
Hypercholesterolemia, Dyslipidemias
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Atorvastatin injection
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia
Eligibility Criteria
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
Sites / Locations
- Frontage Clinical Services
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Change in Baseline LDL-C Concentration
Mean change in LDL-C (mg/dL) from baseline at Day 15
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.
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.
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.
AUC Inf
The AUCinf of atorvastatin following an intravenous injection to a patient at steady-state.
VDss
The volume of distribution at steady state of atorvastatin following an intravenous injection to a patient.
t 1/2
The half-life of atorvastatin following an intravenous injection to a patient at a steady state.
Full Information
NCT ID
NCT03611010
First Posted
July 19, 2018
Last Updated
June 22, 2022
Sponsor
Cumberland Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03611010
Brief Title
Dose-ranging Efficacy and Pharmacokinetics Study of Intravenous Atorvastatin in Hypercholesterolemic Patients
Official Title
Phase II, Dose-ranging Study to Evaluate the Efficacy Dose Response and Pharmacokinetics of Intravenous Atorvastatin in Hypercholesterolemic Patients Previously Controlled With Oral Atorvastatin
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
August 7, 2018 (Actual)
Primary Completion Date
February 17, 2020 (Actual)
Study Completion Date
February 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia, Dyslipidemias
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days
Intervention Type
Drug
Intervention Name(s)
Atorvastatin injection
Intervention Description
statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
Primary Outcome Measure Information:
Title
Efficacy, Number of Participants With Day 15 LDL-C Less Than or Equal to 125% of Baseline LDL-C
Description
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.
Time Frame
Baseline, 15 Days
Secondary Outcome Measure Information:
Title
Efficacy, Number of Participants With Day 15 HDL-C More Than or Equal to 75% Baseline HDL-C
Description
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.
Time Frame
Baseline, 15 Days
Title
Change in Baseline LDL-C Concentration
Description
Mean change in LDL-C (mg/dL) from baseline at Day 15
Time Frame
Baseline, 15 days
Title
Cmax IV
Description
The maximum serum concentration of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Title
Tmax IV
Description
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.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Title
AUC 0-24
Description
The AUC 0-24 of atorvastatin and the 2- and 4-hydroxy active metabolites following an intravenous injection to a patient at steady-state.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Title
AUC Inf
Description
The AUCinf of atorvastatin following an intravenous injection to a patient at steady-state.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Title
VDss
Description
The volume of distribution at steady state of atorvastatin following an intravenous injection to a patient.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
Title
t 1/2
Description
The half-life of atorvastatin following an intravenous injection to a patient at a steady state.
Time Frame
3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Tracey, MD
Organizational Affiliation
Frontage Lab
Official's Role
Principal Investigator
Facility Information:
Facility Name
Frontage Clinical Services
City
Secaucus
State/Province
New Jersey
ZIP/Postal Code
07094
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dose-ranging Efficacy and Pharmacokinetics Study of Intravenous Atorvastatin in Hypercholesterolemic Patients
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