Dyslipidemia
Conditions
Keywords
LCP-AtorFen, Non-HDL cholesterol, Triglycerides, HDL cholesterol, LDL cholesterol, Atorvastatin, Fenofibrate
Brief summary
The current study is designed to test the long-term (12-month) safety and efficacy of LCP-AtorFen, a combination of atorvastatin and fenofibrate, in patients with dyslipidemia
Detailed description
POPULATION: Subjects with mixed dyslipidemia (non-HDL cholesterol \> 130 mg/dL and TG ≥ 150 mg/dL and ≤ 500 mg/dL) who completed the double-blind study (LCP-AtorFen-2001; NCT00504829), met the enrollment criteria (all of the inclusion criteria and none of the exclusion criteria), and elected to enter the open-label extension study. STUDY DESIGN AND DURATION: This is a 52-week, open-label, single-treatment arm with 8 visits (Weeks 0, 4, 8, 12, 24, 36, 48 and 52). A maximum of approximately 200 subjects will enter this open-label safety and efficacy extension study from the LCP AtorFen-2001 double-blind study. All subjects enrolled in this study will receive open-label LCP-AtorFen combination therapy. Visit 1 of the extension study corresponds to the last visit of the double-blind study (Visit 6 or Week 12).
Interventions
DRUGLCP-AtorFen
All subjects will be assigned to receive open-label LCP-AtorFen combination therapy for 52 weeks. Subjects will take a single oral dose of study drug in the evening without regard to meals.
Sponsors
Veloxis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has successfully completed the double-blind study (LCP-AtorFen-2001; NCT00504829). 2. Subject has confirmed his or her willingness to participate in this study after being informed of all aspects of the study by voluntarily signing and dating an informed consent form in accordance with Good Clinical Practice (GCP).
Exclusion criteria
1. Study drug compliance \<70% in the double-blind study. 2. Any ongoing serious adverse event, or any ongoing non-serious moderate or severe adverse event from the double-blind study that is rated as possibly, probably or definitely related to study drug. 3. Resting blood pressure \>/=160 mm Hg systolic and/or \>/=100 mm Hg diastolic. 4. Symptoms of unexplained muscle pain, tenderness or weakness (i.e., signs indicative of possible myopathy), or any diagnosis of myopathy or rhabdomyolysis. 5. Any clinically significant change in physical exam or electrocardiogram from Visit 2 to Visit 6 of the double-blind study. 6. Any clinically significant change from Visit 1 to Visit 6 of the double-blind study in medical history including, but not limited to: a diagnosis of insulin-dependent diabetes mellitus (DM); poorly controlled DM; poorly controlled hypertension; significant renal, pulmonary, hepatic, biliary, or gastrointestinal disease; cancer (except non-melanoma skin cancer); and epilepsy. 7. Unwilling to abstain from medications, supplements, ingredients and herbal therapies that were excluded in the double-blind study and continue to be excluded in the open-label study. 8. Women who are pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential (not surgically sterilized between menarche and menopause) who are not using a medically approved method of contraception. 9. Other exclusion conditions might apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | 52 weeks from DB baseline and 40 weeks from OL baseline | Mean percent changes in non-HDL cholesterol, HDL cholesterol, TG levels from the double-blind (DB) baseline (Week 0) to end-of-treatment (Week 52), and from the open-label (OL) baseline (week 12 of DB study) to end of treatment (Week 52) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | 52 weeks from DB baseline and 40 weeks from OL baseline | Mean percent changes in LDL cholesterol, VLDL, total cholesterol, Apo A-1, and Apo B from the double-blind (DB) baseline (Week 0) to end-of-treatment (Week 52), and from the open-label (OL) baseline (week 12) to end-of-treatment (Week 52) |
Countries
United States
Participant flow
Recruitment details
Of the 192 subjects who completed the double-blind (DB) period, 140 rolled over into the extension study and received at least one dose of open-label (OL) study drug to form the safety population.
Participants by arm
| Arm | Count |
|---|---|
| LCP-AtorFen 40/100mg Data presented by previous double-blind study assignment | 51 |
| Atorvastatin 40 mg Data presented by previous double-blind study assignment | 45 |
| Fenofibrate 145 mg Data presented by previous double-blind study assignment | 44 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 3 |
| Overall Study | DB Study (LCP-AtorFen-2001) AE | 6 | 4 | 4 |
| Overall Study | Laboratory abnormality | 2 | 1 | 4 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 |
| Overall Study | Noncompliance with protocol | 1 | 0 | 4 |
| Overall Study | Other | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | LCP-AtorFen 40/100mg | Atorvastatin 40 mg | Fenofibrate 145 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 10.86 | 55.6 years STANDARD_DEVIATION 9.03 | 57.2 years STANDARD_DEVIATION 11.23 | 55.7 years STANDARD_DEVIATION 10.41 |
| Race/Ethnicity, Customized Amer. Indian /Alaskan | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Hawaiian/Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 46 Participants | 38 Participants | 42 Participants | 126 Participants |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 17 Participants | 55 Participants |
| Sex: Female, Male Male | 33 Participants | 25 Participants | 27 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 45 | 0 / 44 |
| other Total, other adverse events | 12 / 51 | 21 / 45 | 21 / 44 |
| serious Total, serious adverse events | 3 / 51 | 1 / 45 | 3 / 44 |
Outcome results
Primary
Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment
Mean percent changes in non-HDL cholesterol, HDL cholesterol, TG levels from the double-blind (DB) baseline (Week 0) to end-of-treatment (Week 52), and from the open-label (OL) baseline (week 12 of DB study) to end of treatment (Week 52)
Time frame: 52 weeks from DB baseline and 40 weeks from OL baseline
Population: Modified intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol, change from DB baseline | -48.2 percent change | Standard Deviation 13.58 |
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol change from OL baseline | 2.6 percent change | Standard Deviation 22.39 |
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from DB baseline | -53.1 percent change | Standard Deviation 25.31 |
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from OL baseline | 11.4 percent change | Standard Deviation 65.36 |
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from DB baseline | 22.1 percent change | Standard Deviation 21.7 |
| LCP-AtorFen 40/100mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from OL baseline | 2.1 percent change | Standard Deviation 16.9 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from OL baseline | 10.1 percent change | Standard Deviation 17.77 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol, change from DB baseline | -43.6 percent change | Standard Deviation 18.18 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from OL baseline | -19.1 percent change | Standard Deviation 40.42 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from DB baseline | 16.3 percent change | Standard Deviation 18.67 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol change from OL baseline | 2.8 percent change | Standard Deviation 33.67 |
| Atorvastatin 40 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from DB baseline | -51.2 percent change | Standard Deviation 23.23 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol change from OL baseline | -29.6 percent change | Standard Deviation 26.92 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from DB baseline | -42.1 percent change | Standard Deviation 29.96 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from OL baseline | -2.4 percent change | Standard Deviation 15.4 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Triglycerides change from OL baseline | -5.2 percent change | Standard Deviation 53.27 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | Non-HDL cholesterol, change from DB baseline | -42.0 percent change | Standard Deviation 20.49 |
| Fenofibrate 145 mg | Change in Non-HDL Cholesterol, HDL Cholesterol, TG Levels From Baseline to End of Treatment | HDL cholesterol change from DB baseline | 17.5 percent change | Standard Deviation 20.21 |
Secondary
Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment
Mean percent changes in LDL cholesterol, VLDL, total cholesterol, Apo A-1, and Apo B from the double-blind (DB) baseline (Week 0) to end-of-treatment (Week 52), and from the open-label (OL) baseline (week 12) to end-of-treatment (Week 52)
Time frame: 52 weeks from DB baseline and 40 weeks from OL baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo A-1 change from DB baseline | 3.2 Percent change | Standard Deviation 13.21 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from DB baseline | -53.6 Percent change | Standard Deviation 23.98 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo-A-1 change from OL baseline | -1.4 Percent change | Standard Deviation 8.11 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from DB baseline | -42.4 Percent change | Standard Deviation 11.85 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from DB baseline | -44.8 Percent change | Standard Deviation 15.92 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from OL baseline | 3.1 Percent change | Standard Deviation 17.69 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from OL baseline | 12.7 Percent change | Standard Deviation 69.42 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from OL baseline | 2.1 Percent change | Standard Deviation 25.09 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from DB baseline | -36.5 Percent change | Standard Deviation 11.07 |
| LCP-AtorFen 40/100mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from OL baseline | 1.5 Percent change | Standard Deviation 12.95 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo A-1 change from DB baseline | 1.0 Percent change | Standard Deviation 9.88 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from OL baseline | -18.7 Percent change | Standard Deviation 39.97 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from OL baseline | 4.6 Percent change | Standard Deviation 24.54 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo-A-1 change from OL baseline | 1.9 Percent change | Standard Deviation 13.62 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from DB baseline | -51.1 Percent change | Standard Deviation 23.07 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from DB baseline | -39.3 Percent change | Standard Deviation 20.04 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from DB baseline | -38.9 Percent change | Standard Deviation 16.26 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from DB baseline | -33.8 Percent change | Standard Deviation 14.6 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from OL baseline | -1.5 Percent change | Standard Deviation 25.14 |
| Atorvastatin 40 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from OL baseline | 14 Percent change | Standard Deviation 36.29 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from OL baseline | -25.5 Percent change | Standard Deviation 21.59 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from DB baseline | -40.9 Percent change | Standard Deviation 22 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | LDL-C change from OL baseline | -33.6 Percent change | Standard Deviation 24.26 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from DB baseline | -42.0 Percent change | Standard Deviation 29.94 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | VLDL-C change from OL baseline | -5.5 Percent change | Standard Deviation 51.98 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from DB baseline | -32.8 Percent change | Standard Deviation 16.08 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Total-C change from OL baseline | -24.4 Percent change | Standard Deviation 19.04 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo A-1 change from DB baseline | 0.4 Percent change | Standard Deviation 12.5 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo-A-1 change from OL baseline | -5.1 Percent change | Standard Deviation 11.36 |
| Fenofibrate 145 mg | Change in LDL Cholesterol, VLDL, Total Cholesterol, Apo A-1, and Apo B From Baseline to End of Treatment | Apo B change from DB baseline | -36.8 Percent change | Standard Deviation 18.81 |