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Open-label study will titrate doses of intravenous atorvastatin and monitor respective LDL-C levels in hypercholesterolemic patients previously controlled on oral atorvastatin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
|
| Cohort 2 | Experimental | Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
|
| Cohort 3 | Experimental | Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
|
| Cohort 4 | Experimental | Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin injection | Drug | statin (i.e., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor) for injection |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Tracey, MD | Frontage Lab | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Frontage Clinical Services | Secaucus | New Jersey | 07094 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
| FG001 | Cohort 2 | Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
| FG002 | Cohort 3 | Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin during lead-in, then IV study drug for up to 15 days |
| FG003 | Cohort 4 | Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin during lead-in, then SC study drug for up to 15 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Lead-In |
| |||||||||||||
| Period 2: 15 Day Treatment |
|
Safety Population: All subjects who received at least a partial dose of investigational medicinal product. No treated subjects were excluded from the safety population.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Cohort 1 = Baseline daily dose of 10 mg oral atorvastatin receiving either IV or SC study drug |
| BG001 | Cohort 2 | Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Count of Participants | Participants | No | Baseline, 15 Days |
|
15 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vision blurred | Eye disorders | MedDRA (22.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Manager, Clinical Development | Cumberland Pharmaceuticals Inc. | 6155642188 | imaciasperez@cumberlandpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 4, 2019 | May 3, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 10, 2020 | May 3, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D050171 | Dyslipidemias |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 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 |
| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Cohort 3 | Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug |
| BG003 | Cohort 4 | Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Prior Atorvastatin Use or Using Oral Atorvastatin | Count of Participants | Participants |
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| Cohort 2 |
Cohort 2 = Baseline daily dose of 20 mg oral atorvastatin receiving either IV or SC study drug |
| OG002 | Cohort 3 | Cohort 3 = Baseline daily dose of 40 mg oral atorvastatin receiving either IV or SC study drug |
| OG003 | Cohort 4 | Cohort 4 = Baseline daily dose of 20 mg oral atorvastatin receiving either SC study drug |
|
|
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | Baseline, 15 Days |
|
|
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| Secondary | Change in Baseline LDL-C Concentration | Mean change in LDL-C (mg/dL) from baseline at Day 15 | 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. | Posted | Mean | Standard Deviation | mg/dL | Baseline, 15 days |
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|
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| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | mg/mL | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
|
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| Secondary | 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. | 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. | Posted | Median | Full Range | hours | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
|
|
| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
|
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| Secondary | AUC Inf | The AUCinf of atorvastatin following an intravenous injection to a patient at steady-state. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
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| Secondary | VDss | The volume of distribution at steady state of atorvastatin following an intravenous injection to a patient. | 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. | Posted | Mean | Standard Deviation | liter | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
|
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| Secondary | t 1/2 | The half-life of atorvastatin following an intravenous injection to a patient at a steady state. | 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. | Posted | Mean | Standard Deviation | hours | 3 to 7 minutes, 0.5h, 1h 2h, 4h, 6h, 8h, 24h post-dose |
|
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| 0 |
| 14 |
| 0 |
| 14 |
| 4 |
| 14 |
| EG001 | Cohort 2 | 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 | 0 | 14 | 0 | 14 | 1 | 14 |
| EG002 | Cohort 3 | 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 | 0 | 2 | 0 | 2 | 1 | 2 |
| EG003 | Cohort 4 | 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 | 0 | 10 | 0 | 10 | 3 | 10 |
| Injection site pain | General disorders | MedDRA (22.0) | Systematic Assessment |
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| Hypersensitivity | Immune system disorders | MedDRA (22.0) | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
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| Lip injury | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
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| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
|
| 4-Hydroxy Atorvastatin |
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| 4-Hydroxy Atorvastatin |
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| 4-Hydroxy Atorvastatin |
|