Hypercholesteremia
Conditions
Keywords
LDL-C, Lipid Regulator
Brief summary
The purpose of this study was to assess the efficacy, safety, and tolerability of multiple doses of gemcabene 600 mg QD compared to placebo in patients with hypercholesterolemia not adequately controlled on high-intensity or moderate-intensity stable statin therapy. Patients with HeFH, ASCVD, or otherwise uncontrolled, may be included with baseline LDL-C value ≥ 100 mg/dL. Subjects were randomized 1:1 to gemcabene 600 mg once daily (QD) or placebo.
Interventions
DRUGGemcabene
Two 300 mg tablets and 1 placebo tablet administered orally, once daily for 12 weeks.
DRUGPlacebo
Three placebo tablets administered orally once daily for 12 weeks.
Sponsors
NeuroBo Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of written and signed informed consent (by subject or legal guardian) prior to any study-specific procedures; 2. Male or female (neither pregnant or lactating) ≥ 18 years of age at the time of consent; 3. Currently on a stable, low-fat, low-cholesterol diet in combination with allowed statin doses as described in Table 1, with or without ezetimibe 10 mg QD for at least 12 weeks prior to the Screening Visit; 4. Fasting LDL-C value ≥ 100 mg/dL (2.59 mmol/L) at the Screening Visit; 5. Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator; 6. Weight ≥ 50 kg; with a body mass index (BMI) ≤ 45 kg/m2 7. Subjects with Type 2 diabetes who take anti-hyperglycemic agents must be on a stable regimen for at least 3 months, with no planned changes in medications for the study duration.
Exclusion criteria
1. Abnormal liver function test at the Pre-Screening or Screening Visit (AST or ALT) \> 2x ULN (upper limit of normal), total bilirubin \> 1.5x ULN, or alkaline phosphate \> 2x ULN based on appropriate age and gender normal values. Subjects with bilirubin \> 1.5x ULN and a history of Gilbert's syndrome may be included; reflexive direct bilirubin testing will be used to confirm Gilbert's syndrome; 2. Moderate (Grade B) or severe (Grade C) chronic hepatic impairment according to the Child-Pugh classification; 3. Active liver disease (e.g. cirrhosis, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, known diagnosis of HIV or AIDS; 4. Triglyceride value ≥ 500 mg/dL at the Pre-Screening Visit or the Screening Visit; 5. Moderate to severe renal insufficiency define as an estimated GFR \< 60mL/min/1.73m (calculated using the Chronic Kidney Disease Epidemiology Collaboration equation) at the Pre-Screening Visit or Screening Visit; 6. Abnormal urinalysis (proteinuria greater than trace or any male or non-menstruating female with greater than trace hematuria) confirmed by reflexive urine protein:creatinine ration testing; 7. Uncontrolled thyroid disease; hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal or \> 1.5x ULN, respectively, based on results from the Pre-Screening Visit or the Screening Visit. If controlled, treatment should be stable for at least 3 months prior to Screening; 8. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (hemoglobin A1c value \> 8.5% based on results from the Pre-Screening or Screening Visit, or taking a thiazolidinedione (i.e. pioglitazone or rosiglitazone); 9. New York Heart Association Class III or IV heart failure; 10. Myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, or other major cardiovascular events resulting in hospitalization within 3 months of the Screening Visit. Subjects with adequately treated stable angina, per Investigator assessment, may be included; 11. Uncontrolled cardiac arrhythmia or prolonged QT on the Screening Visit or Day 1 prior to dosing ECG (QTcF \> 450 msec for men and \> 470 msec for women) or known family history of prolonged QT or unexplained sudden cardiac death; 12. Uncontrolled hypertension, defined as sitting systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg, and confirmed by repeat measurement; 13. Currently receiving cancer treatments or, in the Investigator's opinion, at risk of relapse for recent cancer; 14. Inadequate wash-out of a PCSK9 inhibitor (8 weeks prior to the Screening Visit), a fibrate lipid-regulating agent (6 weeks prior to the Screening Visit), niacins (4 weeks prior to the Screening Visit), or other lipid-regulating therapies such as bile acid sequestrants (4 weeks prior to the Screening Visit); 15. Hypersensitivity to or a history of significant adverse reactions to any fibrate lipid-regulating agent; 16. Use of any excluded medications or supplements (e.g. potent cytochrome P450 \[CYP\] 3A4 inhibitors as described in Appendix D; 17. History of drug or alcohol abuse within the past year or inability to comply with protocol requirements, including subjects restrictions (see Section 5.6.3); 18. Previously treated with gemcabene (CI-1027), participation in another clinical study of an investigational agent or device concurrently or within 1 month prior the Screening Visit, or use of an investigational agent within 1 month or 5 half-lives (if known), whichever is longer, prior to the Screening Visit; 19. Any other finding which, in the opinion of the Investigator, would compromise the subject's safety or participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in LDL-C at Week 12 | Baseline, Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lipoprotein(a) | Baseline, Weeks 4, 8 and 12 | — |
| Change From Baseline in Lipoprotein(a) | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in High-sensitivity C-reactive Protein | Baseline, Week 12 | — |
| Change From Baseline in High-sensitivity C-reactive Protein | Baseline, Week 12 | — |
| Percent Change From Baseline in Fibrinogen | Baseline, Week 12 | — |
| Change From Baseline in Fibrinogen | Baseline, Week 12 | — |
| Percent Change From Baseline in Serum Amyloid A | Baseline, Week 12 | — |
| Change From Baseline in Serum Amyloid A | Baseline, Week 12 | — |
| Change From Baseline in Apolipoprotein C-III | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein E | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in LDL-C by Statin Intensity Stratum | Baseline, Week 12 | The intensity of statin therapy was determined based on the statin dose.Participants were categorized as high intensity & moderate intensity based on their statin doses. |
| Change From Baseline in LDL-C | Baseline, Weeks 2, 4, 8, 12 and average of weeks 8 and 12 | — |
| Percent Change From Baseline in LDL-C | Baseline, average of weeks 8 and 12 | — |
| Percent Change From Baseline in Non-HDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Change From Baseline in Non-HDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Percent Change From Baseline in TC | Baseline, Weeks 2, 4, 8 and 12 | — |
| Change From Baseline in TC | Baseline, Weeks 2, 4, 8 and 12 | — |
| Percent Change From Baseline in TG | Baseline, Weeks 2, 4, 8 and 12 | — |
| Change From Baseline in TG | Baseline, Weeks 2, 4, 8 and 12 | — |
| Percent Change From Baseline in VLDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Change From Baseline in VLDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Percent Change From Baseline in HDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Change From Baseline in HDL-C | Baseline, Weeks 2, 4, 8 and 12 | — |
| Number of Participants Achieving LDL-C Reduction of ≥10% | Weeks 4, 8 and 12 | — |
| Number of Participants Achieving LDL-C Reduction of ≥15% | Weeks 4, 8 and 12 | — |
| Number of Participants Achieving LDL-C Reduction of ≥20% | Weeks 4, 8 and 12 | — |
| Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein B | Baseline, Weeks 4, 8 and 12 | — |
| Change From Baseline in Apolipoprotein B | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein A-I | Baseline, Weeks 4, 8 and 12 | — |
| Change From Baseline in Apolipoprotein A-I | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein A-II | Baseline, Weeks 4, 8 and 12 | — |
| Change From Baseline in Apolipoprotein A-II | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein C-II | Baseline, Weeks 4, 8 and 12 | — |
| Change From Baseline in Apolipoprotein E | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Apolipoprotein C-III | Baseline, Weeks 4, 8 and 12 | — |
| Percent Change From Baseline in Adiponectin | Baseline, Week 12 | — |
| Change From Baseline in Adiponectin | Baseline, Week 12 | — |
| Change From Baseline in Framingham Risk Score | Baseline, Week 12 | Framingham Risk Score was an estimate of a participant's 10-year risk of developing cardiovascular disease which was computed using sex-specific algorithms based on total point score (range less than negative 3 \[best\] to greater than or equal to 14 \[worst\] for men; less than or equal to negative 2 \[best\] and greater than or equal to 17 \[worst\] for women) : which was derived of participant's age, systolic blood pressure , smoking status, TC, HDL-C, treatment for hypertension, and diabetes status. Reported score is a percentage. Change from baseline calculated as mean at week 12 minus mean at baseline. Negative scores indicate less risk of developing cardiovascular disease. |
| Change From Baseline in Apolipoprotein C-II | Baseline, Weeks 4, 8 and 12 | — |
Countries
United States
Participant flow
Pre-assignment details
Participants who had heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) and were on a statin therapy were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Gemcabene 600 mg Participants on stable statin therapy received 600 mg of Gemcabene orally, once daily for 12 weeks. | 53 |
| Placebo Participants on stable statin therapy received matching placebo orally, once daily for 12 weeks. | 52 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Non-Compliance | 0 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Gemcabene 600 mg |
|---|---|---|---|
| Adiponectin | 6.7 Microgram per milliliter (μg/mL) STANDARD_DEVIATION 4.45 | 6.6 Microgram per milliliter (μg/mL) STANDARD_DEVIATION 3.98 | 6.8 Microgram per milliliter (μg/mL) STANDARD_DEVIATION 4.9 |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 9.62 | 59.0 years STANDARD_DEVIATION 9.67 | 62.7 years STANDARD_DEVIATION 9.3 |
| Apolipoprotein A-I (ApoA-I) | 152.1 mg/dL STANDARD_DEVIATION 23.94 | 148.8 mg/dL STANDARD_DEVIATION 25.45 | 155.3 mg/dL STANDARD_DEVIATION 22.14 |
| Apolipoprotein A-II (ApoA-II) | 36.5 mg/dL STANDARD_DEVIATION 5.62 | 36.0 mg/dL STANDARD_DEVIATION 5.86 | 36.9 mg/dL STANDARD_DEVIATION 5.38 |
| Apolipoprotein B (ApoB) | 104.1 mg/dL STANDARD_DEVIATION 21.22 | 100.1 mg/dL STANDARD_DEVIATION 22.22 | 108.0 mg/dL STANDARD_DEVIATION 19.61 |
| Apolipoprotein C-II (ApoC-II) | 5.5 mg/dL STANDARD_DEVIATION 2.54 | 5.5 mg/dL STANDARD_DEVIATION 2.65 | 5.5 mg/dL STANDARD_DEVIATION 2.45 |
| Apolipoprotein C-III (ApoC-III) | 10.8 mg/dL STANDARD_DEVIATION 3.53 | 10.7 mg/dL STANDARD_DEVIATION 3.69 | 10.9 mg/dL STANDARD_DEVIATION 3.4 |
| Apolipoprotein E (ApoE) | 4.3 mg/dL STANDARD_DEVIATION 1.02 | 4.2 mg/dL STANDARD_DEVIATION 1.08 | 4.3 mg/dL STANDARD_DEVIATION 0.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 45 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Fibrinogen | 457.1 mg/dL STANDARD_DEVIATION 102.95 | 460.7 mg/dL STANDARD_DEVIATION 92.22 | 453.5 mg/dL STANDARD_DEVIATION 113.26 |
| Framingham Risk Score | 16.758 Percentage (%) STANDARD_DEVIATION 12.7583 | 15.381 Percentage (%) STANDARD_DEVIATION 11.4957 | 18.109 Percentage (%) STANDARD_DEVIATION 13.863 |
| High-density lipoprotein cholesterol (HDL-C) | 53.20 mg/dL STANDARD_DEVIATION 13.87 | 51.86 mg/dL STANDARD_DEVIATION 13.097 | 54.51 mg/dL STANDARD_DEVIATION 14.594 |
| High-sensitivity C-reactive protein (hsCRP) | 3.42 milligram per Liter (mg/L) STANDARD_DEVIATION 3.916 | 3.91 milligram per Liter (mg/L) STANDARD_DEVIATION 4.779 | 2.93 milligram per Liter (mg/L) STANDARD_DEVIATION 2.792 |
| LDL-C by Statin intensity stratum High-intensity | 133.97 mg/dL STANDARD_DEVIATION 28.665 | 128.60 mg/dL STANDARD_DEVIATION 28.521 | 139.34 mg/dL STANDARD_DEVIATION 28.356 |
| LDL-C by Statin intensity stratum Moderate-intensity | 126.76 mg/dL STANDARD_DEVIATION 23.681 | 124.54 mg/dL STANDARD_DEVIATION 28.104 | 128.91 mg/dL STANDARD_DEVIATION 18.742 |
| Lipoprotein(a) | 109.1 Nanomole per liter (nmol/L) STANDARD_DEVIATION 113.03 | 113.8 Nanomole per liter (nmol/L) STANDARD_DEVIATION 102.59 | 104.4 Nanomole per liter (nmol/L) STANDARD_DEVIATION 123.23 |
| Low-density lipoprotein cholesterol (LDL-C) | 130.20 Milligram per deciliter (mg/dL) STANDARD_DEVIATION 26.294 | 126.49 Milligram per deciliter (mg/dL) STANDARD_DEVIATION 28.101 | 133.83 Milligram per deciliter (mg/dL) STANDARD_DEVIATION 24.107 |
| Non-high-density lipoprotein cholesterol (non-HDL-C) | 158.28 mg/dL STANDARD_DEVIATION 31.353 | 154.31 mg/dL STANDARD_DEVIATION 32.796 | 162.17 mg/dL STANDARD_DEVIATION 29.664 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 38 Participants | 43 Participants |
| Serum amyloid A | 7.2 mg/dL STANDARD_DEVIATION 816 | 8.6 mg/dL STANDARD_DEVIATION 11.01 | 5.8 mg/dL STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 56 Participants | 27 Participants | 29 Participants |
| Sex: Female, Male Male | 49 Participants | 25 Participants | 24 Participants |
| Total Cholesterol (TC) | 211.47 mg/dL STANDARD_DEVIATION 30.586 | 206.16 mg/dL STANDARD_DEVIATION 31.848 | 216.68 mg/dL STANDARD_DEVIATION 28.643 |
| Triglycerides (TG) | 140.20 mg/dL STANDARD_DEVIATION 62.621 | 138.80 mg/dL STANDARD_DEVIATION 65.088 | 141.57 mg/dL STANDARD_DEVIATION 60.696 |
| Very low-density lipoprotein cholesterol (VLDL-C) | 28.08 mg/dL STANDARD_DEVIATION 12.527 | 27.82 mg/dL STANDARD_DEVIATION 13.048 | 28.34 mg/dL STANDARD_DEVIATION 12.114 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 51 |
| other Total, other adverse events | 33 / 54 | 24 / 51 |
| serious Total, serious adverse events | 0 / 54 | 0 / 51 |
Outcome results
Primary
Percent Change From Baseline in LDL-C at Week 12
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by Last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in LDL-C at Week 12 | -16.03 Percent Change | Standard Error 3.234 |
| Placebo | Percent Change From Baseline in LDL-C at Week 12 | -4.98 Percent Change | Standard Error 3.33 |
Comparison: A 2-sided test with a significance level of 0.05 was used for the comparison.p-value: 0.005795% CI: [-18.81, -3.29]ANCOVA
Secondary
Change From Baseline in Adiponectin
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Adiponectin | 1.2 μg/mL | Standard Deviation 0.32 |
| Placebo | Change From Baseline in Adiponectin | 0.4 μg/mL | Standard Deviation 0.34 |
p-value: 0.05195% CI: [0, 1.5]ANCOVA
Secondary
Change From Baseline in Apolipoprotein A-I
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-I | Week 8 | 6.5 mg/dL | Standard Error 2.36 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-I | Week 12 | 6.9 mg/dL | Standard Error 2.5 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-I | Week 4 | 3.6 mg/dL | Standard Error 2.14 |
| Placebo | Change From Baseline in Apolipoprotein A-I | Week 8 | 4.8 mg/dL | Standard Error 2.45 |
| Placebo | Change From Baseline in Apolipoprotein A-I | Week 12 | 3.3 mg/dL | Standard Error 2.59 |
| Placebo | Change From Baseline in Apolipoprotein A-I | Week 4 | 4.4 mg/dL | Standard Error 2.22 |
Comparison: Week 4p-value: 0.775395% CI: [-5.9, 4.4]ANCOVA
Comparison: Week 8p-value: 0.547295% CI: [-3.9, 7.4]ANCOVA
Comparison: Week 12p-value: 0.240695% CI: [-2.4, 9.6]ANCOVA
Secondary
Change From Baseline in Apolipoprotein A-II
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-II | Week 4 | 0.5 mg/dL | Standard Error 0.54 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-II | Week 8 | 1.1 mg/dL | Standard Error 0.69 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein A-II | Week 12 | 0.9 mg/dL | Standard Error 0.66 |
| Placebo | Change From Baseline in Apolipoprotein A-II | Week 4 | 0.4 mg/dL | Standard Error 0.56 |
| Placebo | Change From Baseline in Apolipoprotein A-II | Week 8 | -0.8 mg/dL | Standard Error 0.71 |
| Placebo | Change From Baseline in Apolipoprotein A-II | Week 12 | -0.7 mg/dL | Standard Error 0.68 |
Comparison: Week 4p-value: 0.91195% CI: [-1.2, 1.4]ANCOVA
Comparison: Week 8p-value: 0.024395% CI: [0.3, 3.5]ANCOVA
Comparison: Week 12p-value: 0.038895% CI: [0.1, 3.2]ANCOVA
Secondary
Change From Baseline in Apolipoprotein B
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein B | Week 4 | -10.6 mg/dL | Standard Deviation 2.74 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein B | Week 8 | -11.1 mg/dL | Standard Deviation 2.64 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein B | Week 12 | -12.0 mg/dL | Standard Deviation 2.86 |
| Placebo | Change From Baseline in Apolipoprotein B | Week 4 | 0.1 mg/dL | Standard Deviation 2.82 |
| Placebo | Change From Baseline in Apolipoprotein B | Week 8 | -7.3 mg/dL | Standard Deviation 2.72 |
| Placebo | Change From Baseline in Apolipoprotein B | Week 12 | -0.4 mg/dL | Standard Deviation 2.95 |
Comparison: Week 4p-value: 0.001895% CI: [-17.3, -4.1]ANCOVA
Comparison: Week 8p-value: 0.243795% CI: [-10.1, 2.6]ANCOVA
Comparison: Week 12p-value: 0.001295% CI: [-18.5, -4.7]ANCOVA
Secondary
Change From Baseline in Apolipoprotein C-II
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-II | Week 4 | 0.5 mg/dL | Standard Error 0.19 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-II | Week 8 | 0.8 mg/dL | Standard Error 0.24 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-II | Week 12 | 0.8 mg/dL | Standard Error 0.27 |
| Placebo | Change From Baseline in Apolipoprotein C-II | Week 4 | 0.00 mg/dL | Standard Error 0.2 |
| Placebo | Change From Baseline in Apolipoprotein C-II | Week 8 | -0.3 mg/dL | Standard Error 0.25 |
| Placebo | Change From Baseline in Apolipoprotein C-II | Week 12 | 0.00 mg/dL | Standard Error 0.27 |
Comparison: Week 4p-value: 0.017995% CI: [0.1, 1]ANCOVA
Comparison: Week 8p-value: 0.000395% CI: [0.5, 1.7]ANCOVA
Comparison: Week 12p-value: 0.009595% CI: [0.2, 1.5]ANCOVA
Secondary
Change From Baseline in Apolipoprotein C-III
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-III | Week 12 | 0.3 mg/dL | Standard Deviation 0.44 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-III | Week 4 | 0.0 mg/dL | Standard Deviation 0.39 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein C-III | Week 8 | 0.0 mg/dL | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Apolipoprotein C-III | Week 4 | 1.4 mg/dL | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Apolipoprotein C-III | Week 8 | 0.0 mg/dL | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Apolipoprotein C-III | Week 12 | 0.9 mg/dL | Standard Deviation 0.45 |
Comparison: Week 4p-value: 0.004895% CI: [-2.3, -0.4]ANCOVA
Comparison: Week 8p-value: 0.906495% CI: [-0.9, 0.8]ANCOVA
Comparison: Week 12p-value: 0.250595% CI: [-1.7, 0.4]ANCOVA
Secondary
Change From Baseline in Apolipoprotein E
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein E | Week 4 | -0.3 mg/dL | Standard Error 0.11 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein E | Week 8 | -0.3 mg/dL | Standard Error 0.12 |
| Gemcabene 600 mg | Change From Baseline in Apolipoprotein E | Week 12 | -0.4 mg/dL | Standard Error 0.15 |
| Placebo | Change From Baseline in Apolipoprotein E | Week 4 | 0.3 mg/dL | Standard Error 0.12 |
| Placebo | Change From Baseline in Apolipoprotein E | Week 8 | -0.1 mg/dL | Standard Error 0.13 |
| Placebo | Change From Baseline in Apolipoprotein E | Week 12 | 0.3 mg/dL | Standard Error 0.15 |
Comparison: Week 4p-value: <0.000195% CI: [-0.9, -0.3]ANCOVA
Comparison: Week 8p-value: 0.077195% CI: [-0.6, 0]ANCOVA
Comparison: Week 12p-value: 0.000695% CI: [-1, -0.3]ANCOVA
Secondary
Change From Baseline in Fibrinogen
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Fibrinogen | 9.0 mg/dL | Standard Error 13.69 |
| Placebo | Change From Baseline in Fibrinogen | 41.4 mg/dL | Standard Error 14 |
p-value: 0.051795% CI: [-65.1, 0.2]ANCOVA
Secondary
Change From Baseline in Framingham Risk Score
Framingham Risk Score was an estimate of a participant's 10-year risk of developing cardiovascular disease which was computed using sex-specific algorithms based on total point score (range less than negative 3 \[best\] to greater than or equal to 14 \[worst\] for men; less than or equal to negative 2 \[best\] and greater than or equal to 17 \[worst\] for women) : which was derived of participant's age, systolic blood pressure , smoking status, TC, HDL-C, treatment for hypertension, and diabetes status. Reported score is a percentage. Change from baseline calculated as mean at week 12 minus mean at baseline. Negative scores indicate less risk of developing cardiovascular disease.
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Framingham Risk Score | -2.051 Percentage (%) | Standard Deviation 4.1599 |
| Placebo | Change From Baseline in Framingham Risk Score | -0.850 Percentage (%) | Standard Deviation 4.9889 |
Secondary
Change From Baseline in HDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in HDL-C | Week 2 | -1.33 mg/dL | Standard Error 0.964 |
| Gemcabene 600 mg | Change From Baseline in HDL-C | Week 4 | -0.48 mg/dL | Standard Error 1.004 |
| Gemcabene 600 mg | Change From Baseline in HDL-C | Week 8 | 1.35 mg/dL | Standard Error 1.099 |
| Gemcabene 600 mg | Change From Baseline in HDL-C | Week 12 | 2.22 mg/dL | Standard Error 1.182 |
| Placebo | Change From Baseline in HDL-C | Week 12 | 0.62 mg/dL | Standard Error 1.216 |
| Placebo | Change From Baseline in HDL-C | Week 2 | -0.41 mg/dL | Standard Error 0.991 |
| Placebo | Change From Baseline in HDL-C | Week 8 | 0.11 mg/dL | Standard Error 1.13 |
| Placebo | Change From Baseline in HDL-C | Week 4 | 0.65 mg/dL | Standard Error 1.033 |
Comparison: Week 2p-value: 0.427895% CI: [-3.23, 1.38]ANCOVA
Comparison: Week 4p-value: 0.352995% CI: [-3.53, 1.27]ANCOVA
Comparison: Week 8p-value: 0.352295% CI: [-1.39, 3.86]ANCOVA
Comparison: Week 12p-value: 0.263595% CI: [-1.22, 4.42]ANCOVA
Secondary
Change From Baseline in High-sensitivity C-reactive Protein
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in High-sensitivity C-reactive Protein | -0.40 mg/L | Standard Deviation 0.495 |
| Placebo | Change From Baseline in High-sensitivity C-reactive Protein | 0.44 mg/L | Standard Deviation 0.513 |
p-value: 0.164895% CI: [-2.03, 0.35]ANCOVA
Secondary
Change From Baseline in LDL-C
Time frame: Baseline, Weeks 2, 4, 8, 12 and average of weeks 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in LDL-C | Week 4 | -20.72 mg/dL | Standard Error 3.958 |
| Gemcabene 600 mg | Change From Baseline in LDL-C | Week 12 | -20.40 mg/dL | Standard Error 4.059 |
| Gemcabene 600 mg | Change From Baseline in LDL-C | Week 8 | -17.97 mg/dL | Standard Error 4.172 |
| Gemcabene 600 mg | Change From Baseline in LDL-C | Average of week 8 and 12 | -19.19 mg/dL | Standard Error 3.717 |
| Gemcabene 600 mg | Change From Baseline in LDL-C | Week 2 | -25.69 mg/dL | Standard Error 3.731 |
| Placebo | Change From Baseline in LDL-C | Average of week 8 and 12 | -13.32 mg/dL | Standard Error 3.827 |
| Placebo | Change From Baseline in LDL-C | Week 2 | -15.60 mg/dL | Standard Error 3.842 |
| Placebo | Change From Baseline in LDL-C | Week 4 | -11.32 mg/dL | Standard Error 4.076 |
| Placebo | Change From Baseline in LDL-C | Week 8 | -18.86 mg/dL | Standard Error 4.296 |
| Placebo | Change From Baseline in LDL-C | Week 12 | -7.77 mg/dL | Standard Error 4.18 |
Comparison: Week 2p-value: 0.027595% CI: [-19.04, -1.14]ANCOVA
Comparison: Week 4.p-value: 0.052495% CI: [-18.9, 0.1]ANCOVA
Comparison: Week 8p-value: 0.860295% CI: [-9.12, 10.9]ANCOVA
Comparison: Week 12p-value: 0.011595% CI: [-22.37, -2.89]ANCOVA
Comparison: Average of week 8 and 12p-value: 0.194595% CI: [-14.79, 3.05]ANCOVA
Secondary
Change From Baseline in Lipoprotein(a)
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Lipoprotein(a) | Week 4 | -1.9 nmol/L | Standard Error 3.97 |
| Gemcabene 600 mg | Change From Baseline in Lipoprotein(a) | Week 8 | 2.1 nmol/L | Standard Error 3.16 |
| Gemcabene 600 mg | Change From Baseline in Lipoprotein(a) | Week 12 | 2.1 nmol/L | Standard Error 4 |
| Placebo | Change From Baseline in Lipoprotein(a) | Week 4 | -3.6 nmol/L | Standard Error 4.06 |
| Placebo | Change From Baseline in Lipoprotein(a) | Week 8 | -2.6 nmol/L | Standard Error 3.23 |
| Placebo | Change From Baseline in Lipoprotein(a) | Week 12 | 1.7 nmol/L | Standard Error 4.09 |
Comparison: Week 4p-value: 0.727695% CI: [-7.8, 11.1]ANCOVA
Comparison: Week 8p-value: 0.221895% CI: [-2.9, 12.2]ANCOVA
Comparison: Week 12p-value: 0.94295% CI: [-9.2, 9.8]ANCOVA
Secondary
Change From Baseline in Non-HDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Non-HDL-C | Week 4 | -21.88 mg/dL | Standard Error 4.318 |
| Gemcabene 600 mg | Change From Baseline in Non-HDL-C | Week 12 | -23.21 mg/dL | Standard Error 4.451 |
| Gemcabene 600 mg | Change From Baseline in Non-HDL-C | Week 8 | -19.45 mg/dL | Standard Error 4.551 |
| Gemcabene 600 mg | Change From Baseline in Non-HDL-C | Week 2 | -29.21 mg/dL | Standard Error 4.088 |
| Placebo | Change From Baseline in Non-HDL-C | Week 8 | -18.86 mg/dL | Standard Error 4.673 |
| Placebo | Change From Baseline in Non-HDL-C | Week 4 | -6.33 mg/dL | Standard Error 4.433 |
| Placebo | Change From Baseline in Non-HDL-C | Week 2 | -16.55 mg/dL | Standard Error 4.197 |
| Placebo | Change From Baseline in Non-HDL-C | Week 12 | -6.62 mg/dL | Standard Error 4.57 |
Comparison: Week 2p-value: 0.011795% CI: [-22.45, -2.88]ANCOVA
Comparison: Week 4p-value: 0.003695% CI: [-25.88, -5.21]ANCOVA
Comparison: Week 8p-value: 0.914795% CI: [-11.48, 10.31]ANCOVA
Comparison: Week 12p-value: 0.002695% CI: [-27.24, -5.93]ANCOVA
Secondary
Change From Baseline in Serum Amyloid A
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in Serum Amyloid A | -0.5 mg/dL | Standard Error 2.87 |
| Placebo | Change From Baseline in Serum Amyloid A | 2.6 mg/dL | Standard Error 2.93 |
p-value: 0.386495% CI: [-10, 3.9]ANCOVA
Secondary
Change From Baseline in TC
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in TC | Week 4 | -22.37 mg/dL | Standard Error 4.514 |
| Gemcabene 600 mg | Change From Baseline in TC | Week 2 | -30.47 mg/dL | Standard Error 4.331 |
| Gemcabene 600 mg | Change From Baseline in TC | Week 12 | -20.90 mg/dL | Standard Error 4.5 |
| Gemcabene 600 mg | Change From Baseline in TC | Week 8 | -18.10 mg/dL | Standard Error 4.741 |
| Placebo | Change From Baseline in TC | Week 12 | -6.92 mg/dL | Standard Error 4.654 |
| Placebo | Change From Baseline in TC | Week 4 | -6.08 mg/dL | Standard Error 4.669 |
| Placebo | Change From Baseline in TC | Week 8 | -19.68 mg/dL | Standard Error 4.903 |
| Placebo | Change From Baseline in TC | Week 2 | -17.73 mg/dL | Standard Error 4.479 |
Comparison: Week 2p-value: 0.017395% CI: [-23.19, -2.3]ANCOVA
Comparison: Week 4p-value: 0.003895% CI: [-27.17, -5.4]ANCOVA
Comparison: Week 8p-value: 0.784695% CI: [-9.85, 13.01]ANCOVA
Comparison: Week 12p-value: 0.012195% CI: [-24.83, -3.13]ANCOVA
Secondary
Change From Baseline in TG
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in TG | Week 2 | -18.88 mg/dL | Standard Error 6.322 |
| Gemcabene 600 mg | Change From Baseline in TG | Week 4 | -6.08 mg/dL | Standard Error 7.132 |
| Gemcabene 600 mg | Change From Baseline in TG | Week 8 | -8.17 mg/dL | Standard Error 5.238 |
| Gemcabene 600 mg | Change From Baseline in TG | Week 12 | -15.94 mg/dL | Standard Error 10.194 |
| Placebo | Change From Baseline in TG | Week 12 | 13.64 mg/dL | Standard Error 10.412 |
| Placebo | Change From Baseline in TG | Week 2 | 0.65 mg/dL | Standard Error 6.457 |
| Placebo | Change From Baseline in TG | Week 8 | 0.16 mg/dL | Standard Error 5.35 |
| Placebo | Change From Baseline in TG | Week 4 | 27.56 mg/dL | Standard Error 7.284 |
Comparison: Week 2p-value: 0.011395% CI: [-34.55, -4.51]ANCOVA
Comparison: Week 4p-value: 0.000295% CI: [-50.58, -16.69]ANCOVA
Comparison: Week 8p-value: 0.187395% CI: [-20.77, 4.12]ANCOVA
Comparison: Week 12p-value: 0.017295% CI: [-53.8, -5.37]ANCOVA
Secondary
Change From Baseline in VLDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Change From Baseline in VLDL-C | Week 2 | -3.64 mg/dL | Standard Error 1.124 |
| Gemcabene 600 mg | Change From Baseline in VLDL-C | Week 8 | -1.56 mg/dL | Standard Error 1.034 |
| Gemcabene 600 mg | Change From Baseline in VLDL-C | Week 4 | -1.27 mg/dL | Standard Error 1.371 |
| Gemcabene 600 mg | Change From Baseline in VLDL-C | Week 12 | -2.89 mg/dL | Standard Error 1.279 |
| Placebo | Change From Baseline in VLDL-C | Week 12 | 1.11 mg/dL | Standard Error 1.306 |
| Placebo | Change From Baseline in VLDL-C | Week 2 | -0.69 mg/dL | Standard Error 1.148 |
| Placebo | Change From Baseline in VLDL-C | Week 4 | 5.02 mg/dL | Standard Error 1.4 |
| Placebo | Change From Baseline in VLDL-C | Week 8 | 0.01 mg/dL | Standard Error 1.056 |
Comparison: Week 2p-value: 0.030895% CI: [-5.62, -0.28]ANCOVA
Comparison: Week 4p-value: 0.000295% CI: [-9.56, -3.04]ANCOVA
Comparison: Week 8p-value: 0.205695% CI: [-4.03, 0.88]ANCOVA
Comparison: Week 12p-value: 0.010395% CI: [-7.04, -0.96]ANCOVA
Secondary
Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L)
Time frame: Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcabene 600 mg | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 4 | 21 Participants |
| Gemcabene 600 mg | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 8 | 20 Participants |
| Gemcabene 600 mg | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 12 | 21 Participants |
| Placebo | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 4 | 13 Participants |
| Placebo | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 8 | 22 Participants |
| Placebo | Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L) | Week 12 | 15 Participants |
Comparison: Week 4p-value: 0.011595% CI: [1.34, 10.2]Regression, Logistic
Comparison: Week 8p-value: 0.756695% CI: [0.48, 2.75]Regression, Logistic
Comparison: Week 12p-value: 0.029895% CI: [1.11, 7.88]Regression, Logistic
Secondary
Number of Participants Achieving LDL-C Reduction of ≥10%
Time frame: Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 4 | 33 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 8 | 34 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 12 | 35 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 4 | 22 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 8 | 29 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥10% | Week 12 | 23 Participants |
Comparison: Week 4p-value: 0.046495% CI: [1.01, 4.93]Regression, Logistic
Comparison: Week 8p-value: 0.527895% CI: [0.58, 2.92]Regression, Logistic
Comparison: Week 12p-value: 0.035995% CI: [1.06, 5.27]Regression, Logistic
Secondary
Number of Participants Achieving LDL-C Reduction of ≥15%
Time frame: Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 4 | 28 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 8 | 29 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 12 | 35 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 4 | 16 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 8 | 22 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥15% | Week 12 | 15 Participants |
Comparison: Week 4p-value: 0.026895% CI: [1.11, 5.61]Regression, Logistic
Comparison: Week 8p-value: 0.275595% CI: [0.7, 3.41]Regression, Logistic
Comparison: Week 12p-value: 0.000395% CI: [2.05, 10.94]Regression, Logistic
Secondary
Number of Participants Achieving LDL-C Reduction of ≥20%
Time frame: Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 4 | 25 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 8 | 19 Participants |
| Gemcabene 600 mg | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 12 | 22 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 4 | 11 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 8 | 14 Participants |
| Placebo | Number of Participants Achieving LDL-C Reduction of ≥20% | Week 12 | 10 Participants |
Comparison: Week 4p-value: 0.007995% CI: [1.36, 7.8]Regression, Logistic
Comparison: Week 8p-value: 0.400295% CI: [0.62, 3.35]Regression, Logistic
Comparison: Week 12p-value: 0.014295% CI: [1.25, 7.59]Regression, Logistic
Secondary
Percent Change From Baseline in Adiponectin
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Adiponectin | 17.7 Percent Change | Standard Error 4.1 |
| Placebo | Percent Change From Baseline in Adiponectin | 5.4 Percent Change | Standard Error 4.26 |
p-value: 0.014595% CI: [2.5, 22]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein A-I
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-I | Week 4 | 3.0 Percent Change | Standard Deviation 1.45 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-I | Week 8 | 4.6 Percent Change | Standard Deviation 1.53 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-I | Week 12 | 4.7 Percent Change | Standard Deviation 1.6 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-I | Week 4 | 3.7 Percent Change | Standard Deviation 1.51 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-I | Week 8 | 3.8 Percent Change | Standard Deviation 1.59 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-I | Week 12 | 2.8 Percent Change | Standard Deviation 1.66 |
Comparison: Week 4p-value: 0.683295% CI: [-4.2, 2.8]ANCOVA
Comparison: Week 8p-value: 0.67495% CI: [-2.9, 4.5]ANCOVA
Comparison: Week 12p-value: 0.337995% CI: [-2, 5.7]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein A-II
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-II | Week 4 | 2.1 Percent Change | Standard Error 1.49 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-II | Week 8 | 3.8 Percent Change | Standard Error 1.84 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein A-II | Week 12 | 3.7 Percent Change | Standard Error 1.8 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-II | Week 4 | 1.9 Percent Change | Standard Error 1.54 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-II | Week 8 | -1.4 Percent Change | Standard Error 1.9 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-II | Week 12 | -0.9 Percent Change | Standard Error 1.86 |
Comparison: Week 4p-value: 0.902895% CI: [-3.3, 3.8]ANCOVA
Comparison: Week 8p-value: 0.019995% CI: [0.8, 9.6]ANCOVA
Comparison: Week 12p-value: 0.036995% CI: [0.3, 8.9]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein B | Week 4 | -8.7 Percent Change | Standard Deviation 2.81 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein B | Week 8 | -9.8 Percent Change | Standard Deviation 2.53 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein B | Week 12 | -10.5 Percent Change | Standard Deviation 2.79 |
| Placebo | Percent Change From Baseline in Apolipoprotein B | Week 4 | 1.8 Percent Change | Standard Deviation 2.89 |
| Placebo | Percent Change From Baseline in Apolipoprotein B | Week 8 | -5.5 Percent Change | Standard Deviation 2.6 |
| Placebo | Percent Change From Baseline in Apolipoprotein B | Week 12 | 1.0 Percent Change | Standard Deviation 2.87 |
Comparison: Week 4p-value: 0.002995% CI: [-17.2, -3.7]ANCOVA
Comparison: Week 8p-value: 0.166695% CI: [-10.4, 1.8]ANCOVA
Comparison: Week 12p-value: 0.00195% CI: [-18.2, -4.8]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein C-II
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-II | Week 8 | 30.7 Percent Change | Standard Error 6.95 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-II | Week 12 | 27.3 Percent Change | Standard Error 7.07 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-II | Week 4 | 20.0 Percent Change | Standard Error 5.34 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-II | Week 4 | 13.1 Percent Change | Standard Error 5.46 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-II | Week 8 | 3.9 Percent Change | Standard Error 7.1 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-II | Week 12 | 7.2 Percent Change | Standard Error 7.23 |
Comparison: Week 4p-value: 0.279995% CI: [-5.7, 19.6]ANCOVA
Comparison: Week 8p-value: 0.001895% CI: [10.2, 43.3]ANCOVA
Comparison: Week 12p-value: 0.019795% CI: [3.3, 36.9]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein C-III
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-III | Week 4 | 0.4 Percent Change | Standard Error 3.61 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-III | Week 8 | 2.0 Percent Change | Standard Error 3.56 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein C-III | Week 12 | 3.5 Percent Change | Standard Error 4.32 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-III | Week 4 | 12.6 Percent Change | Standard Error 3.69 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-III | Week 8 | 1.8 Percent Change | Standard Error 3.64 |
| Placebo | Percent Change From Baseline in Apolipoprotein C-III | Week 12 | 9.7 Percent Change | Standard Error 4.42 |
Comparison: Week 4p-value: 0.005795% CI: [-20.8, -3.6]ANCOVA
Comparison: Week 8p-value: 0.966595% CI: [-8.3, 8.6]ANCOVA
Comparison: Week 12p-value: 0.235895% CI: [-16.4, 4.1]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein E
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein E | Week 12 | -7.8 Percent Change | Standard Error 3.16 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein E | Week 4 | -6.7 Percent Change | Standard Error 2.86 |
| Gemcabene 600 mg | Percent Change From Baseline in Apolipoprotein E | Week 8 | -7.3 Percent Change | Standard Error 2.89 |
| Placebo | Percent Change From Baseline in Apolipoprotein E | Week 12 | 7.5 Percent Change | Standard Error 3.25 |
| Placebo | Percent Change From Baseline in Apolipoprotein E | Week 4 | 9.1 Percent Change | Standard Error 2.94 |
| Placebo | Percent Change From Baseline in Apolipoprotein E | Week 8 | -0.1 Percent Change | Standard Error 2.97 |
Comparison: Week 4p-value: <0.000195% CI: [-22.6, -9]ANCOVA
Comparison: Week 8p-value: 0.040695% CI: [-14, -0.3]ANCOVA
Comparison: Week 12p-value: <0.000195% CI: [-22.8, -7.8]ANCOVA
Secondary
Percent Change From Baseline in Fibrinogen
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Fibrinogen | 61.8 Percent Change | Standard Error 47.59 |
| Placebo | Percent Change From Baseline in Fibrinogen | 20.3 Percent Change | Standard Error 48.69 |
p-value: 0.470195% CI: [-72.1, 155.1]ANCOVA
Secondary
Percent Change From Baseline in HDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in HDL-C | Week 2 | -2.73 Percent Change | Standard Error 1.771 |
| Gemcabene 600 mg | Percent Change From Baseline in HDL-C | Week 4 | -0.39 Percent Change | Standard Error 1.888 |
| Gemcabene 600 mg | Percent Change From Baseline in HDL-C | Week 8 | 2.34 Percent Change | Standard Error 2.112 |
| Gemcabene 600 mg | Percent Change From Baseline in HDL-C | Week 12 | 3.86 Percent Change | Standard Error 2.129 |
| Placebo | Percent Change From Baseline in HDL-C | Week 12 | 1.08 Percent Change | Standard Error 2.189 |
| Placebo | Percent Change From Baseline in HDL-C | Week 2 | -0.60 Percent Change | Standard Error 1.821 |
| Placebo | Percent Change From Baseline in HDL-C | Week 8 | 0.37 Percent Change | Standard Error 2.171 |
| Placebo | Percent Change From Baseline in HDL-C | Week 4 | 2.01 Percent Change | Standard Error 1.941 |
p-value: 0.319395% CI: [-6.36, 2.09]ANCOVA
Comparison: Week 4p-value: 0.293295% CI: [-6.91, 2.11]ANCOVA
Comparison: Week 8p-value: 0.438395% CI: [-3.06, 7.02]ANCOVA
Comparison: Week 12p-value: 0.281495% CI: [-2.31, 7.86]ANCOVA
Secondary
Percent Change From Baseline in High-sensitivity C-reactive Protein
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein | 57.33 Percent Change | Standard Error 64.525 |
| Placebo | Percent Change From Baseline in High-sensitivity C-reactive Protein | 24.76 Percent Change | Standard Error 66.946 |
p-value: 0.678695% CI: [-122.98, 188.12]ANCOVA
Secondary
Percent Change From Baseline in LDL-C
Time frame: Baseline, average of weeks 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in LDL-C | -15.15 Percent Change | Standard Error 2.921 |
| Placebo | Percent Change From Baseline in LDL-C | -9.27 Percent Change | Standard Error 3.008 |
p-value: 0.099195% CI: [-12.89, 1.13]ANCOVA
Secondary
Percent Change From Baseline in LDL-C by Statin Intensity Stratum
The intensity of statin therapy was determined based on the statin dose.Participants were categorized as high intensity & moderate intensity based on their statin doses.
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, Number analyzed signifies those participants who were evaluable in each category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in LDL-C by Statin Intensity Stratum | Moderate intensity | -19.58 Percent Change | Standard Error 4.739 |
| Gemcabene 600 mg | Percent Change From Baseline in LDL-C by Statin Intensity Stratum | High intensity | -13.05 Percent Change | Standard Error 4.732 |
| Placebo | Percent Change From Baseline in LDL-C by Statin Intensity Stratum | High intensity | -1.25 Percent Change | Standard Error 4.943 |
| Placebo | Percent Change From Baseline in LDL-C by Statin Intensity Stratum | Moderate intensity | -8.94 Percent Change | Standard Error 4.766 |
Comparison: High-Intensity.p-value: 0.064895% CI: [-24.35, 0.75]ANCOVA
Comparison: Moderate Intensity.p-value: 0.039895% CI: [-20.77, -0.51]ANCOVA
Secondary
Percent Change From Baseline in Lipoprotein(a)
Time frame: Baseline, Weeks 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Lipoprotein(a) | Week 4 | 3.5 Percent Change | Standard Error 4.61 |
| Gemcabene 600 mg | Percent Change From Baseline in Lipoprotein(a) | Week 8 | 3.9 Percent Change | Standard Error 3.94 |
| Gemcabene 600 mg | Percent Change From Baseline in Lipoprotein(a) | Week 12 | 4.2 Percent Change | Standard Error 5.18 |
| Placebo | Percent Change From Baseline in Lipoprotein(a) | Week 4 | -5.1 Percent Change | Standard Error 4.72 |
| Placebo | Percent Change From Baseline in Lipoprotein(a) | Week 8 | -4.0 Percent Change | Standard Error 4.03 |
| Placebo | Percent Change From Baseline in Lipoprotein(a) | Week 12 | 0.1 Percent Change | Standard Error 5.3 |
Comparison: Week 4p-value: 0.12195% CI: [-2.3, 19.6]ANCOVA
Comparison: Week 8p-value: 0.094895% CI: [-1.4, 17.3]ANCOVA
Comparison: Week 12p-value: 0.511395% CI: [-8.2, 16.4]ANCOVA
Secondary
Percent Change From Baseline in Non-HDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Non-HDL-C | Week 2 | -17.60 Percent Change | Standard Error 2.397 |
| Gemcabene 600 mg | Percent Change From Baseline in Non-HDL-C | Week 4 | -13.27 Percent Change | Standard Error 2.664 |
| Gemcabene 600 mg | Percent Change From Baseline in Non-HDL-C | Week 8 | -12.35 Percent Change | Standard Error 2.831 |
| Gemcabene 600 mg | Percent Change From Baseline in Non-HDL-C | Week 12 | -14.48 Percent Change | Standard Error 2.86 |
| Placebo | Percent Change From Baseline in Non-HDL-C | Week 12 | -3.79 Percent Change | Standard Error 2.936 |
| Placebo | Percent Change From Baseline in Non-HDL-C | Week 2 | -10.01 Percent Change | Standard Error 2.461 |
| Placebo | Percent Change From Baseline in Non-HDL-C | Week 8 | -11.41 Percent Change | Standard Error 2.907 |
| Placebo | Percent Change From Baseline in Non-HDL-C | Week 4 | -3.71 Percent Change | Standard Error 2.735 |
Comparison: Week 2p-value: 0.010195% CI: [-13.32, -1.84]ANCOVA
Comparison: Week 4p-value: 0.003795% CI: [-15.94, -3.18]ANCOVA
Comparison: Week 8p-value: 0.783995% CI: [-7.72, 5.84]ANCOVA
Comparison: Week 12p-value: 0.002595% CI: [-17.53, -3.84]ANCOVA
Secondary
Percent Change From Baseline in Serum Amyloid A
Time frame: Baseline, Week 12
Population: FAS Population. Missing values were imputed by LOCF. Here, overall number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in Serum Amyloid A | 34.6 Percent Change | Standard Error 69.71 |
| Placebo | Percent Change From Baseline in Serum Amyloid A | 44.1 Percent Change | Standard Error 71.04 |
p-value: 0.911195% CI: [-177.8, 158.8]ANCOVA
Secondary
Percent Change From Baseline in TC
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in TC | Week 2 | -14.10 Percent Change | Standard Error 1.923 |
| Gemcabene 600 mg | Percent Change From Baseline in TC | Week 4 | -10.35 Percent Change | Standard Error 2.136 |
| Gemcabene 600 mg | Percent Change From Baseline in TC | Week 8 | -8.77 Percent Change | Standard Error 2.236 |
| Gemcabene 600 mg | Percent Change From Baseline in TC | Week 12 | -9.79 Percent Change | Standard Error 2.161 |
| Placebo | Percent Change From Baseline in TC | Week 12 | -2.90 Percent Change | Standard Error 2.235 |
| Placebo | Percent Change From Baseline in TC | Week 2 | -7.97 Percent Change | Standard Error 1.989 |
| Placebo | Percent Change From Baseline in TC | Week 8 | -8.88 Percent Change | Standard Error 2.313 |
| Placebo | Percent Change From Baseline in TC | Week 4 | -2.62 Percent Change | Standard Error 2.209 |
Comparison: Week 2p-value: 0.010195% CI: [-10.77, -1.5]ANCOVA
Comparison: Week 4p-value: 0.003695% CI: [-12.89, -2.58]ANCOVA
Comparison: Week 8p-value: 0.965395% CI: [-5.27, 5.51]ANCOVA
Comparison: Week 12p-value: 0.010195% CI: [-12.1, -1.68]ANCOVA
Secondary
Percent Change From Baseline in TG
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in TG | Week 2 | -10.58 Percent Change | Standard Error 4.251 |
| Gemcabene 600 mg | Percent Change From Baseline in TG | Week 8 | -4.94 Percent Change | Standard Error 3.743 |
| Gemcabene 600 mg | Percent Change From Baseline in TG | Week 4 | -6.28 Percent Change | Standard Error 4.706 |
| Gemcabene 600 mg | Percent Change From Baseline in TG | Week 12 | -8.22 Percent Change | Standard Error 5.245 |
| Placebo | Percent Change From Baseline in TG | Week 4 | 17.31 Percent Change | Standard Error 4.807 |
| Placebo | Percent Change From Baseline in TG | Week 2 | 2.64 Percent Change | Standard Error 4.342 |
| Placebo | Percent Change From Baseline in TG | Week 12 | 7.42 Percent Change | Standard Error 5.356 |
| Placebo | Percent Change From Baseline in TG | Week 8 | 1.76 Percent Change | Standard Error 3.823 |
Comparison: Week 2p-value: 0.010895% CI: [-23.32, -3.12]ANCOVA
Comparison: Week 4p-value: <0.000195% CI: [-34.78, -12.42]ANCOVA
Comparison: Week 8p-value: 0.137695% CI: [-15.6, 2.18]ANCOVA
p-value: 0.014495% CI: [-28.1, -3.18]ANCOVA
Secondary
Percent Change From Baseline in VLDL-C
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: FAS Population. Missing values were imputed by LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcabene 600 mg | Percent Change From Baseline in VLDL-C | Week 2 | -10.55 Percent Change | Standard Deviation 4.104 |
| Gemcabene 600 mg | Percent Change From Baseline in VLDL-C | Week 4 | -6.63 Percent Change | Standard Deviation 4.632 |
| Gemcabene 600 mg | Percent Change From Baseline in VLDL-C | Week 8 | -4.69 Percent Change | Standard Deviation 3.687 |
| Gemcabene 600 mg | Percent Change From Baseline in VLDL-C | Week 12 | -7.69 Percent Change | Standard Deviation 4.155 |
| Placebo | Percent Change From Baseline in VLDL-C | Week 12 | 3.94 Percent Change | Standard Deviation 4.243 |
| Placebo | Percent Change From Baseline in VLDL-C | Week 2 | 0.97 Percent Change | Standard Deviation 4.192 |
| Placebo | Percent Change From Baseline in VLDL-C | Week 8 | 1.74 Percent Change | Standard Deviation 3.765 |
| Placebo | Percent Change From Baseline in VLDL-C | Week 4 | 16.38 Percent Change | Standard Deviation 4.731 |
Comparison: Week 2p-value: 0.02195% CI: [-21.27, -1.77]ANCOVA
Comparison: Week 4p-value: <0.000195% CI: [-34.02, -12.01]ANCOVA
Comparison: Week 8p-value: 0.148395% CI: [-15.19, 2.33]ANCOVA
Comparison: Week 12p-value: 0.021495% CI: [-21.5, -1.76]ANCOVA