Trial Outcomes & Findings for Dose-ranging Efficacy and Pharmacokinetics Study of Intravenous Atorvastatin in Hypercholesterolemic Patients (NCT NCT03611010)

NCT ID: NCT03611010

Last Updated: 2022-07-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Baseline, 15 Days

Results posted on

2022-07-15

Participant Flow

Enrollment occurred between 07Aug2018 and 24Feb2020. Three types of patients, categorized by statin use prior to study participation were eligible: patients taking oral atorvastatin, patients taking statins other than atorvastatin, patient not taking any statins prior to study. In Amendment 03. the fourth 80mg dose was eliminated and the 15 days IV route administration was changed to subcutaneous administration.

Participant milestones

Participant milestones
Measure
Cohort 1
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 2
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 3
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days
Period 1: Lead-In
STARTED
14
14
2
10
Period 1: Lead-In
COMPLETED
14
14
2
10
Period 1: Lead-In
NOT COMPLETED
0
0
0
0
Period 2: 15 Day Treatment
STARTED
14
14
2
10
Period 2: 15 Day Treatment
COMPLETED
13
14
2
10
Period 2: 15 Day Treatment
NOT COMPLETED
1
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Cohort 1
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 2
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 3
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days
Period 2: 15 Day Treatment
Inaccessible veins
1
0
0
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cohort 1
n=14 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=14 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
n=10 Participants
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Total
n=40 Participants
Total of all reporting groups
Age, Continuous
44.8 years
STANDARD_DEVIATION 9.74 • n=5 Participants
51.4 years
STANDARD_DEVIATION 8.21 • n=7 Participants
46.0 years
STANDARD_DEVIATION 18.38 • n=5 Participants
50.4 years
STANDARD_DEVIATION 10.47 • n=4 Participants
48.6 years
STANDARD_DEVIATION 9.9 • n=21 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
5 Participants
n=7 Participants
1 Participants
n=5 Participants
5 Participants
n=4 Participants
17 Participants
n=21 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
9 Participants
n=7 Participants
1 Participants
n=5 Participants
5 Participants
n=4 Participants
23 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
7 Participants
n=5 Participants
5 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
17 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
7 Participants
n=5 Participants
9 Participants
n=7 Participants
1 Participants
n=5 Participants
6 Participants
n=4 Participants
23 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
1 Participants
n=21 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=5 Participants
6 Participants
n=7 Participants
0 Participants
n=5 Participants
4 Participants
n=4 Participants
15 Participants
n=21 Participants
Race (NIH/OMB)
White
9 Participants
n=5 Participants
8 Participants
n=7 Participants
2 Participants
n=5 Participants
5 Participants
n=4 Participants
24 Participants
n=21 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Prior Atorvastatin Use or Using Oral Atorvastatin
Prior Atorvastatin Use or Using Oral Atorvastatin
6 Participants
n=5 Participants
4 Participants
n=7 Participants
1 Participants
n=5 Participants
5 Participants
n=4 Participants
16 Participants
n=21 Participants
Prior Atorvastatin Use or Using Oral Atorvastatin
Prior Statin Other than Atorvastatin Use
1 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
2 Participants
n=21 Participants
Prior Atorvastatin Use or Using Oral Atorvastatin
No Prior Statin Use
7 Participants
n=5 Participants
9 Participants
n=7 Participants
1 Participants
n=5 Participants
5 Participants
n=4 Participants
22 Participants
n=21 Participants

PRIMARY outcome

Timeframe: Baseline, 15 Days

Population: Efficacy Population: A completed group of subjects that 1) finished the two-week treatment period, 2) provided a Day 15 LDL-C level, and 3) took the final targeted dose for that cohort comprised the four efficacy populations.

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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
n=9 Participants
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Efficacy, Number of Participants With Day 15 LDL-C Less Than or Equal to 125% of Baseline LDL-C
9 Participants
9 Participants
1 Participants
7 Participants

SECONDARY outcome

Timeframe: Baseline, 15 Days

Population: Efficacy Population: A completed group of subjects that 1) finished the two-week treatment period, 2) provided a Day 15 LDL-C level, and 3) took the final targeted dose for that cohort comprised the four efficacy populations.

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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
n=9 Participants
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Efficacy, Number of Participants With Day 15 HDL-C More Than or Equal to 75% Baseline HDL-C
11 Participants
13 Participants
1 Participants
9 Participants

SECONDARY outcome

Timeframe: Baseline, 15 days

Population: Efficacy Population: A completed group of subjects that 1) finished the two-week treatment period, 2) provided a Day 15 LDL-C level, and 3) took the final targeted dose for that cohort comprised the four efficacy populations.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
n=9 Participants
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Change in Baseline LDL-C Concentration
12.36 mg/dL
Standard Deviation 14.740
2.62 mg/dL
Standard Deviation 34.844
27.50 mg/dL
Standard Deviation 14.849
11.22 mg/dL
Standard Deviation 13.283

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Cmax IV
Atorvastatin
284.33 mg/mL
Standard Deviation 189.540
830.34 mg/mL
Standard Deviation 1141.919
507.50 mg/mL
Standard Deviation 443.456
Cmax IV
2-Hydroxy Atorvastatin
0.40 mg/mL
Standard Deviation 0.87
1.23 mg/mL
Standard Deviation 0.450
3.23 mg/mL
Standard Deviation 1.987
Cmax IV
4-Hydroxy Atorvastatin
0.24 mg/mL
Standard Deviation 0
0.30 mg/mL
Standard Deviation 0.163
0.75 mg/mL
Standard Deviation 0.370

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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.

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
Tmax IV
Atorvastatin
0.08 hours
Interval 0.0 to 0.5
0.08 hours
Interval 0.0 to 0.5
0.15 hours
Interval 0.1 to 0.2
Tmax IV
2-Hydroxy Atorvastatin
6.00 hours
Interval 6.0 to 8.0
6.0 hours
Interval 2.0 to 8.0
5.00 hours
Interval 4.0 to 6.0
Tmax IV
4-Hydroxy Atorvastatin
0.08 hours
Interval 0.0 to 0.1
6.0 hours
Interval 0.0 to 8.0
8.0 hours
Interval 8.0 to 8.0

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
AUC 0-24
Atorvastatin
72.12 ng*hr/mL
Standard Deviation 31.216
137.04 ng*hr/mL
Standard Deviation 134.608
212.00 ng*hr/mL
Standard Deviation 89.095
AUC 0-24
2-Hydroxy Atorvastatin
3.35 ng*hr/mL
Standard Deviation 2.603
16.76 ng*hr/mL
Standard Deviation 6.283
49.20 ng*hr/mL
Standard Deviation 26.698
AUC 0-24
4-Hydroxy Atorvastatin
NA ng*hr/mL
Standard Deviation NA
Values are below the level of detection
5.45 ng*hr/mL
Standard Deviation 3.691
12.65 ng*hr/mL
Standard Deviation 5.303

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
AUC Inf
72.19 ng*hr/mL
Standard Deviation 31.196
167.32 ng*hr/mL
Standard Deviation 138.099
217.00 ng*hr/mL
Standard Deviation 89.095

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
VDss
71.86 liter
Standard Deviation 81.475
135.53 liter
Standard Deviation 145.579
182.85 liter
Standard Deviation 140.219

SECONDARY outcome

Timeframe: 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose

Population: Pharmacokinetic Population: All subjects in the Efficacy Population who had no major protocol deviations and who had sufficient plasma atorvastatin concentration data for reliable estimates of the key PK variables for each of the four baseline cohorts.

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

Outcome measures

Outcome measures
Measure
Cohort 1
n=11 Participants
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug
Cohort 2
n=13 Participants
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug
Cohort 3
n=2 Participants
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug
Cohort 4
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug
t 1/2
4.79 hours
Standard Deviation 4.311
6.22 hours
Standard Deviation 1.884
6.38 hours
Standard Deviation 0.085

Adverse Events

Cohort 1

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Cohort 2

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Cohort 3

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Cohort 4

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Cohort 1
n=14 participants at risk
Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days Atorvastatin injection: statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
Cohort 2
n=14 participants at risk
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days Atorvastatin injection: statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
Cohort 3
n=2 participants at risk
Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days Atorvastatin injection: statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
Cohort 4
n=10 participants at risk
Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days Atorvastatin injection: statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection
Eye disorders
Vision blurred
7.1%
1/14 • Number of events 1 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
0.00%
0/10 • 15 days
General disorders
Injection site pain
0.00%
0/14 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
10.0%
1/10 • Number of events 1 • 15 days
Immune system disorders
Hypersensitivity
7.1%
1/14 • Number of events 1 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
0.00%
0/10 • 15 days
Infections and infestations
Viral infection
0.00%
0/14 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
10.0%
1/10 • Number of events 1 • 15 days
Injury, poisoning and procedural complications
Lip injury
0.00%
0/14 • 15 days
7.1%
1/14 • Number of events 1 • 15 days
0.00%
0/2 • 15 days
0.00%
0/10 • 15 days
Investigations
Alanine aminotransferase increased
0.00%
0/14 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
10.0%
1/10 • Number of events 1 • 15 days
Investigations
Aspartate aminotransferase increased
0.00%
0/14 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
10.0%
1/10 • Number of events 1 • 15 days
Musculoskeletal and connective tissue disorders
Arthralgia
7.1%
1/14 • Number of events 1 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
0.00%
0/10 • 15 days
Nervous system disorders
Headache
14.3%
2/14 • Number of events 2 • 15 days
0.00%
0/14 • 15 days
0.00%
0/2 • 15 days
0.00%
0/10 • 15 days
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/14 • 15 days
0.00%
0/14 • 15 days
50.0%
1/2 • Number of events 1 • 15 days
0.00%
0/10 • 15 days

Additional Information

Senior Manager, Clinical Development

Cumberland Pharmaceuticals Inc.

Phone: 6155642188

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place