Atherogenic Dyslipidemia, Obesity Associated Disorder
Conditions
Keywords
Extended Release Niacin, Fenofibrate, treatment, Obesity, Atherogenic Dyslipidemia
Brief summary
Atherogenic Dyslipidemia (AD) is a risk-conferring lipid/lipoprotein profile that comprises a higher proportion of small LDL particles, reduced HDL-C, and increased triglycerides. It is characteristically seen in patients with obesity, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus and has emerged as an important marker for the increased cardiovascular disease (CVD) risk observed in these populations. Optimal cardiovascular risk reduction in patients exhibiting the lipid triad of AD requires integrated pharmacotherapy to normalize HDL-C, Triglyceride (TG) and LDL-C levels. Recent studies have focused on optimizing treatment for AD and compare the efficacy and tolerability of combined lipid-altering drug based therapies, however, an optimal pharmacologic approach has not yet been established. The present study was intended to evaluate the restorative efficacy of Extended Release Niacin (ER Niacin) and Fenofibrate as mono and combination therapies , as well as their safety and tolerability in females with obesity-induced AD.
Detailed description
Study Setting: The present study is a single blinded placebo-controlled randomized clinical trial, in which target individuals were obese females (BMI≥30 kg/m2), within the age of 20-60 years, attending the Obesity research and therapy unit of Al-Kindy College of Medicine, University of Baghdad (Baghdad, Iraq), throughout the period from 1st October 2014 to 15th March 2015. Study Protocol: Target individuals with fulfill devoid of exclusion criteria, were further screened and only candidates with conventional diagnosis of AD, as confirmed by a fasting serum TG \>150 mg/dl coincide with an HDL-C of less than 50 mg/dl, were considered to be enrolled. Finally, and successive to a comprehensible concise for the expected benefits and side effects on top of the commitment to the entire protocol, eligible candidates settled for participation were provided with a written informed consent. Enrollment: 1. Therapeutic Lifestyle Changes (TLC) Run-in Period: Each and every eligible candidate was enrolled in a four-week TLC run-in (or lead-in) period to exclude responders and to obtain baseline data for non-responders prior to randomization. 2. Randomization and Treatment Allocation: TLC non-responders with persistent AD were randomly allocated to one of the four treatment arms. In order to ensure a periodical balance among all study groups in the course of treatment allocation, permuted-block randomization with a block size of four was implemented and the system produced by this approach was adopted for the sequential random assignment of patients to treatment arms. . Discontinuation of Treatment: Although the absence of published consensus on drug discontinuation in the face of laboratory abnormalities has permitted a spectrum of indefinite decisions, mainly driven by clinical experience, clinical status and tolerability of the patient. For the present study discontinuation of treatment is considered if: 1. Adverse events including flushing, nausea, vomiting, muscle pain, or dizziness turn sever enough to surpass patient's tolerability. 2. Estimated glomerular filtration rate (eGFR) is reduced to ˂ 60ml/min per 1.73 m2 indicating renal insufficiency. 3. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) increased to\>3 Upper Limit of Normal (ULN) with the appearance of nausea, vomiting, fatigue, right upper quadrant pain or tenderness, fever, and/or rash. 4. Serum uric acid exceeds the critical value of 6mg/dl. Assessment of Treatments Responses: Responses to the different treatments arms, in terms of efficacy and safety, are assessed by analyzing clinical and laboratory data collected at each visit over the entire course of the study, including a thorough medical history and previous medication records. Statistical Analysis: All statistical analyses were executed via the statistical package SPSS version 17.0 (SPSS, Inc.). Prior to analysis, Shapiro-Wilk test was used for assessing the normality of distributions for continuous variables, with the data expressed as the mean ± standard error (SE). Analysis of variance (ANOVA) was applied to compare the means of baseline characteristics among different treatments groups. Comprising the influence of the baseline level as a covariate, analysis of covariance (ANCOVA), embracing the least significant difference (LSD) for pair-wise comparison, was applied to assess treatment effects and safety profiles among different arms. Results were evaluated in terms of adjusted end line levels and percent changes from baseline levels. Multivariate Analysis of Covariance (MANCOVA), on the other hand, with further adjustments for relevant covariates was conducted whenever needed. Probability of less than 0.05 was considered statistically significant.
Interventions
Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
OTHERPlacebo
DRUGFenofibrate
DIETARY_SUPPLEMENTWax Matrix Extended Release Niacin (WMER Niacin)
Sponsors
Al-Kindy College of Medicine
Lewai Sharki Abdulaziz, MSc PhD
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* BMI≥30 kg/m2. * Conventional diagnosis of atherogenic dyslipidemia, confirmed by a fasting serum TG more than150 mg/dl coincide with an HDL-C of less than 50 mg/dl.
Exclusion criteria
* The use of any antilipidemic medication. * Findings suggestive for renal dysfunction (eGFR˂60ml/min per 1.73 m2). * Findings suggestive for hepatic insufficiency (ALT and/or AST˃2ULN). * Clinical or laboratory findings suggestive for thyroid dysfunction. * Established diagnosis of Diabetes Mellitus. * History of gout, hyperuricemia, or on hypouricemic agents. * Active peptic ulcer. * Pregnancy, or nursing mothers. * Alcohol or tobacco consumption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes Serum Triglyceride Levels | Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments. | Assessments involve the measurement of serum Triglyceride (TG) level. |
| Changes in Serum Lipoprotein Cholesterol Levels | Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments. | Assessments involve the measurement of serum Total (TC), High density lipoprotein (HDL-C) and direct Low density lipoprotein (d-LDL-C) cholesterol levels. Serum non HDL-C levels is calculated by subtracting HDL-C from TC. Serum Remnant cholesterol (RC) is calculated by subtracting HDL-C and d-LDL-C from TC. |
| Changes in Serum Apolipoprotein Levels | Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments. | Assessments involve the measurement of serum Apolipoprotein A1 (Apo A1) and B (Apo B) levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Serum Enzymes Levels | Changes from baseline were assessed at the end of the eighth week of treatments. | Assessments involve the measurement of serum enzymes including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Creatine Kinase (CK) levels. |
| Changes in Serum Fasting Glucose Levels. | Changes from baseline were assessed at the end eighth week of treatments. | Assessments involve the measurement of serum fasting glucose levels. |
| Adverse Events | Changes from baseline were assessed at the end of the eighth week of treatments. | Assessments comprise the total number of participants complicating and reporting muscle pain,flushing, nausea, vomiting, and dizziness. As part of the complete safety profile of each arm,other specific reported adverse event are presented in the Adverse Event Module. |
| Changes in Systolic and Diastolic Blood Pressure | Changes from baseline were assessed at the end of the eighth week of treatments. | Assessments involve the measurement of systolic and diastolic blood pressure. Patients were allowed to rest for 15 minutes in sitting position, and Walgreens Homedics WGNBPA-540 upper arm blood pressure monitor (Walgreens, China), was used for the measurement of blood pressure. Three consecutive readings were taken at 1 minute interval, and systolic and diastolic blood pressure were calculated as the mean of the last two readings. |
| Changes in Estimated Glomerular Filtration Rate (eGFR) | Changes from baseline were assessed at the end of the eighth week of treatments. | Assessments involve the measurement of serum creatinine which is used to calculate eGFR using the CKD-EPI equation (2009) . |
| Changes in Serum Uric Acid Levels | Changes from baseline were assessed at the end of the eighth week of treatments. | Assessments involve the measurement of serum uric acid levels |
Countries
Iraq
Participant flow
Recruitment details
Obese females (BMI≥30 kg/m2), within the age of 20-60 years, attending the Obesity research and therapy unit of Al-Kindy College of Medicine, Baghdad, Iraq, throughout the period from 1st October 2014 to 15th March 2015, were screened for preliminary eligibility.
Pre-assignment details
Out of the 161 obese females settled for participation, Atherogenic dyslipidemia (AD) was diagnosed in 69(42.9%) patients, all of whom were enrolled in Therapeutic Lifestyle Changes (TLC) run-in period. AD was averted by TLC in 12(17.4%) patients. The remaining 57(82.6%) non-responding patients were randomly allocated to one of the four study arms.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Non-responders to four-week therapeutic lifestyle changes run-in period, will start to receive an after lunch daily single placebo capsule for eight weeks.
Therapeutic Lifestyle Changes: Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Placebo | 12 |
| Fenofibrate Monotherapy Non-responders to four-week therapeutic lifestyle changes run-in period, will start to receive an after lunch 200mg daily single dose of fenofibrate (Lipanthyl® 200 mg micronized fenofibrate capsule, Abbott Laboratories Fournier) for eight weeks.
Therapeutic Lifestyle Changes: Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Fenofibrate | 15 |
| WMER Niacin Monotherapy Non-responders to four-week therapeutic lifestyle changes run-in period, will start to receive a night-time 500 mg daily single dose of Wax Matrix Extended Release Niacin (WMER Niacin, ENDUR-ACIN®500mg, Endurance Products Company, Oregon USA) for one week, titrated up to 1000 mg by adding a daily morning-time ENDUR-ACIN®500mg tablet for the next seven weeks.
Therapeutic Lifestyle Changes: Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Wax Matrix Extended Release Niacin (WMER Niacin) | 14 |
| Combination Therapy Non-responders to four-week therapeutic lifestyle changes run-in period, will start to receive an after lunch 200mg daily single dose of fenofibrate for eight weeks, in combination with a night-time 500 mg daily single dose of WMER Niacin for one week, titrated up to 1000mg by adding a daily morning-time ENDUR-ACIN®500mg tablet for the next seven weeks.
Therapeutic Lifestyle Changes: Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Fenofibrate
Wax Matrix Extended Release Niacin (WMER Niacin) | 13 |
| Total | 54 |
Baseline characteristics
| Characteristic | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 2.5 | 37.3 years STANDARD_DEVIATION 2 | 36.6 years STANDARD_DEVIATION 2.1 | 40.2 years STANDARD_DEVIATION 2.2 | 37.6 years STANDARD_DEVIATION 2.2 |
| Body Mass Index (BMI) | 38.9 kg/m^2 STANDARD_DEVIATION 2.1 | 41.5 kg/m^2 STANDARD_DEVIATION 1.7 | 42.0 kg/m^2 STANDARD_DEVIATION 1.7 | 39.7 kg/m^2 STANDARD_DEVIATION 1.8 | 40.6 kg/m^2 STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 14 Participants | 13 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 0 / 12 | 0 / 15 | 7 / 14 | 3 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 15 | 0 / 14 | 0 / 13 |
Outcome results
Primary
Changes in Serum Apolipoprotein Levels
Assessments involve the measurement of serum Apolipoprotein A1 (Apo A1) and B (Apo B) levels.
Time frame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Serum Apolipoprotein Levels | Baseline Apo A1 | 130.8 mg/dl | Standard Error 8.7 |
| Placebo | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo B | 124.7 mg/dl | Standard Error 6.4 |
| Placebo | Changes in Serum Apolipoprotein Levels | Baseline Apo B | 134.1 mg/dl | Standard Error 7.5 |
| Placebo | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo A1 | 130.2 mg/dl | Standard Error 10.4 |
| Fenofibrate Monotherapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo A1 | 155.9 mg/dl | Standard Error 9.3 |
| Fenofibrate Monotherapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo B | 106.7 mg/dl | Standard Error 5.7 |
| Fenofibrate Monotherapy | Changes in Serum Apolipoprotein Levels | Baseline Apo A1 | 143.8 mg/dl | Standard Error 7.1 |
| Fenofibrate Monotherapy | Changes in Serum Apolipoprotein Levels | Baseline Apo B | 141.8 mg/dl | Standard Error 6.1 |
| WMER Niacin Monotherapy | Changes in Serum Apolipoprotein Levels | Baseline Apo B | 123.0 mg/dl | Standard Error 6.3 |
| WMER Niacin Monotherapy | Changes in Serum Apolipoprotein Levels | Baseline Apo A1 | 150.1 mg/dl | Standard Error 7.4 |
| WMER Niacin Monotherapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo B | 111.1 mg/dl | Standard Error 5.7 |
| WMER Niacin Monotherapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo A1 | 134.2 mg/dl | Standard Error 9.3 |
| Combination Therapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo B | 101.7 mg/dl | Standard Error 6 |
| Combination Therapy | Changes in Serum Apolipoprotein Levels | Baseline Apo A1 | 150.0 mg/dl | Standard Error 7.7 |
| Combination Therapy | Changes in Serum Apolipoprotein Levels | Baseline Apo B | 133.1 mg/dl | Standard Error 6.6 |
| Combination Therapy | Changes in Serum Apolipoprotein Levels | Adjusted End line Apo A1 | 162.3 mg/dl | Standard Error 9.7 |
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline ApoA1 level as a covariate, with further adjustments for baseline TG and HDL-C levels.p-value: 0.058MANCOVA
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline ApoB level as a covariate, with further adjustments for baselineTC, Non HDL-C, dLDL-C, and RC .p-value: 0.067MANCOVA
Primary
Changes in Serum Lipoprotein Cholesterol Levels
Assessments involve the measurement of serum Total (TC), High density lipoprotein (HDL-C) and direct Low density lipoprotein (d-LDL-C) cholesterol levels. Serum non HDL-C levels is calculated by subtracting HDL-C from TC. Serum Remnant cholesterol (RC) is calculated by subtracting HDL-C and d-LDL-C from TC.
Time frame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line non HDL-C | 166.4 mg/dl | Standard Error 7.7 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Baseline TC | 203.1 mg/dl | Standard Error 11.4 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line d-LDL-C | 115.7 mg/dl | Standard Error 6.6 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Baseline d-LDL-C | 120.0 mg/dl | Standard Error 7.5 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Baseline HDL-C | 30.9 mg/dl | Standard Error 2.1 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line TC | 198.4 mg/dl | Standard Error 7.4 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line HDL-C | 32.0 mg/dl | Standard Error 1.4 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line RC | 50.7 mg/dl | Standard Error 4.8 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Baseline RC | 52.3 mg/dl | Standard Error 8.4 |
| Placebo | Changes in Serum Lipoprotein Cholesterol Levels | Baseline non HDL-C | 172.3 mg/dl | Standard Error 11.3 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line d-LDL-C | 103.6 mg/dl | Standard Error 5.9 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line non HDL-C | 134.1 mg/dl | Standard Error 6.9 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line RC | 30.3 mg/dl | Standard Error 4.3 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline HDL-C | 32.1 mg/dl | Standard Error 1.7 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline TC | 190.7 mg/dl | Standard Error 9.3 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline non HDL-C | 158.6 mg/dl | Standard Error 9.2 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline d-LDL-C | 108.9 mg/dl | Standard Error 6.2 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline RC | 49.7 mg/dl | Standard Error 6.8 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line TC | 171.1 mg/dl | Standard Error 6.7 |
| Fenofibrate Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line HDL-C | 37.2 mg/dl | Standard Error 1.3 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line d-LDL-C | 103.3 mg/dl | Standard Error 5.9 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line RC | 35.7 mg/dl | Standard Error 4.3 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line HDL-C | 38.3 mg/dl | Standard Error 1.3 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline RC | 34.9 mg/dl | Standard Error 7.1 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line non HDL-C | 138.7 mg/dl | Standard Error 6.9 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline d-LDL-C | 120.1 mg/dl | Standard Error 6.4 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline HDL-C | 34.2 mg/dl | Standard Error 1.8 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline TC | 189.1 mg/dl | Standard Error 9.6 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line TC | 177.3 mg/dl | Standard Error 6.6 |
| WMER Niacin Monotherapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline non HDL-C | 154.9 mg/dl | Standard Error 9.5 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line RC | 22.1 mg/dl | Standard Error 4.5 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline TC | 219.5 mg/dl | Standard Error 10 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline HDL-C | 29.7 mg/dl | Standard Error 1.8 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline d-LDL-C | 129.3 mg/dl | Standard Error 6.6 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline non HDL-C | 189.7 mg/dl | Standard Error 9.9 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Baseline RC | 60.5 mg/dl | Standard Error 7.3 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line TC | 179.9 mg/dl | Standard Error 6.4 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line HDL-C | 42.8 mg/dl | Standard Error 1.3 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line d-LDL-C | 115.0 mg/dl | Standard Error 6.2 |
| Combination Therapy | Changes in Serum Lipoprotein Cholesterol Levels | Adjusted End line non HDL-C | 136.3 mg/dl | Standard Error 7.2 |
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline TC level as a covariate, with further adjustments for baseline Non HDL-C and d-LDL-C.p-value: 0.06MANCOVA
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline HDL-C level as a covariate, with further adjustments for baselineTG, ApoA1levels.p-value: 0.0001MANCOVA
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline d-LDL-C level as a covariate, with further adjustments for baseline TC and Non HDL-C .p-value: 0.334MANCOVA
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline Non HDL-C level as a covariate, with further adjustments for baseline TC and d-LDL-C.p-value: 0.012MANCOVA
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline RC level as a covariate, with further adjustments for baselineTC, Non HDL-C, d-LDL-C, and ApoB.p-value: 0.001MANCOVA
Primary
Changes Serum Triglyceride Levels
Assessments involve the measurement of serum Triglyceride (TG) level.
Time frame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes Serum Triglyceride Levels | Baseline TG levels | 223.1 mg/dl | Standard Error 23.4 |
| Placebo | Changes Serum Triglyceride Levels | Adjusted End line TG levels | 220.2 mg/dl | Standard Error 12.8 |
| Fenofibrate Monotherapy | Changes Serum Triglyceride Levels | Adjusted End line TG levels | 133.7 mg/dl | Standard Error 11.4 |
| Fenofibrate Monotherapy | Changes Serum Triglyceride Levels | Baseline TG levels | 241.2 mg/dl | Standard Error 19.1 |
| WMER Niacin Monotherapy | Changes Serum Triglyceride Levels | Baseline TG levels | 227.0 mg/dl | Standard Error 19.7 |
| WMER Niacin Monotherapy | Changes Serum Triglyceride Levels | Adjusted End line TG levels | 164.0 mg/dl | Standard Error 11.4 |
| Combination Therapy | Changes Serum Triglyceride Levels | Baseline TG levels | 267.2 mg/dl | Standard Error 20.5 |
| Combination Therapy | Changes Serum Triglyceride Levels | Adjusted End line TG levels | 136.1 mg/dl | Standard Error 12 |
Comparison: Multivariate Analysis of Covariance (MANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline TG level as a covariate, with further adjustments for baseline HDL-C, ApoA1levels.p-value: 0.0001MANCOVA
Secondary
Adverse Events
Assessments comprise the total number of participants complicating and reporting muscle pain,flushing, nausea, vomiting, and dizziness. As part of the complete safety profile of each arm,other specific reported adverse event are presented in the Adverse Event Module.
Time frame: Changes from baseline were assessed at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Adverse Events | Muscle Pain | 0 Participants |
| Placebo | Adverse Events | Flushing | 0 Participants |
| Placebo | Adverse Events | Nausea/Vomiting | 0 Participants |
| Placebo | Adverse Events | Dizziness | 0 Participants |
| Fenofibrate Monotherapy | Adverse Events | Flushing | 0 Participants |
| Fenofibrate Monotherapy | Adverse Events | Nausea/Vomiting | 0 Participants |
| Fenofibrate Monotherapy | Adverse Events | Dizziness | 0 Participants |
| Fenofibrate Monotherapy | Adverse Events | Muscle Pain | 0 Participants |
| WMER Niacin Monotherapy | Adverse Events | Nausea/Vomiting | 3 Participants |
| WMER Niacin Monotherapy | Adverse Events | Flushing | 1 Participants |
| WMER Niacin Monotherapy | Adverse Events | Dizziness | 0 Participants |
| WMER Niacin Monotherapy | Adverse Events | Muscle Pain | 0 Participants |
| Combination Therapy | Adverse Events | Dizziness | 1 Participants |
| Combination Therapy | Adverse Events | Flushing | 0 Participants |
| Combination Therapy | Adverse Events | Muscle Pain | 1 Participants |
| Combination Therapy | Adverse Events | Nausea/Vomiting | 1 Participants |
Secondary
Changes in Estimated Glomerular Filtration Rate (eGFR)
Assessments involve the measurement of serum creatinine which is used to calculate eGFR using the CKD-EPI equation (2009) .
Time frame: Changes from baseline were assessed at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Estimated Glomerular Filtration Rate (eGFR) | Baseline eGFR | 89.8 ml/min per 1.73 m^2 | Standard Error 4.8 |
| Placebo | Changes in Estimated Glomerular Filtration Rate (eGFR) | Adjusted End line eGFR | 83.1 ml/min per 1.73 m^2 | Standard Error 3.4 |
| Fenofibrate Monotherapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Adjusted End line eGFR | 83.2 ml/min per 1.73 m^2 | Standard Error 3.1 |
| Fenofibrate Monotherapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Baseline eGFR | 86.5 ml/min per 1.73 m^2 | Standard Error 3.9 |
| WMER Niacin Monotherapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Baseline eGFR | 91.0 ml/min per 1.73 m^2 | Standard Error 4.1 |
| WMER Niacin Monotherapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Adjusted End line eGFR | 82.9 ml/min per 1.73 m^2 | Standard Error 3.2 |
| Combination Therapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Baseline eGFR | 85.2 ml/min per 1.73 m^2 | Standard Error 4.2 |
| Combination Therapy | Changes in Estimated Glomerular Filtration Rate (eGFR) | Adjusted End line eGFR | 79.2 ml/min per 1.73 m^2 | Standard Error 3.3 |
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline eGFR level as a covariate.p-value: 0.786ANCOVA
Secondary
Changes in Serum Enzymes Levels
Assessments involve the measurement of serum enzymes including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Creatine Kinase (CK) levels.
Time frame: Changes from baseline were assessed at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Serum Enzymes Levels | Adjusted End line ALT | 15.4 IU/L | Standard Error 0.6 |
| Placebo | Changes in Serum Enzymes Levels | Adjusted End line AST | 18.9 IU/L | Standard Error 0.8 |
| Placebo | Changes in Serum Enzymes Levels | Baseline CK | 28.0 IU/L | Standard Error 4.7 |
| Placebo | Changes in Serum Enzymes Levels | Baseline AST | 17.1 IU/L | Standard Error 1.6 |
| Placebo | Changes in Serum Enzymes Levels | Baseline ALT | 13.1 IU/L | Standard Error 1.4 |
| Placebo | Changes in Serum Enzymes Levels | Adjusted End line CK | 27.3 IU/L | Standard Error 4.7 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line CK | 34.9 IU/L | Standard Error 4.2 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Baseline ALT | 16.3 IU/L | Standard Error 1.2 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line AST | 17.3 IU/L | Standard Error 0.8 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line ALT | 14.4 IU/L | Standard Error 0.5 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Baseline AST | 18.8 IU/L | Standard Error 1.3 |
| Fenofibrate Monotherapy | Changes in Serum Enzymes Levels | Baseline CK | 29.1 IU/L | Standard Error 3.8 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Baseline AST | 17.0 IU/L | Standard Error 1.4 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Baseline CK | 26.9 IU/L | Standard Error 4 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Baseline ALT | 16.0 IU/L | Standard Error 1.2 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line AST | 18.0 IU/L | Standard Error 0.8 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line ALT | 16.4 IU/L | Standard Error 0.5 |
| WMER Niacin Monotherapy | Changes in Serum Enzymes Levels | Adjusted End line CK | 27.4 IU/L | Standard Error 4.4 |
| Combination Therapy | Changes in Serum Enzymes Levels | Baseline ALT | 17.8 IU/L | Standard Error 1.2 |
| Combination Therapy | Changes in Serum Enzymes Levels | Baseline AST | 18.9 IU/L | Standard Error 1.4 |
| Combination Therapy | Changes in Serum Enzymes Levels | Adjusted End line ALT | 16.2 IU/L | Standard Error 0.6 |
| Combination Therapy | Changes in Serum Enzymes Levels | Adjusted End line CK | 28.2 IU/L | Standard Error 4.5 |
| Combination Therapy | Changes in Serum Enzymes Levels | Adjusted End line AST | 19.6 IU/L | Standard Error 0.8 |
| Combination Therapy | Changes in Serum Enzymes Levels | Baseline CK | 28.0 IU/L | Standard Error 4.1 |
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline AST level as a covariate.p-value: 0.201ANCOVA
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline ALT level as a covariate.p-value: 0.033ANCOVA
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline CK level as a covariate.p-value: 0.511ANCOVA
Secondary
Changes in Serum Fasting Glucose Levels.
Assessments involve the measurement of serum fasting glucose levels.
Time frame: Changes from baseline were assessed at the end eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Serum Fasting Glucose Levels. | Adjusted End line serum fasting glucose | 91.3 mg/dl | Standard Error 2.3 |
| Placebo | Changes in Serum Fasting Glucose Levels. | Baseline serum fasting glucose | 93.5 mg/dl | Standard Error 3.9 |
| Fenofibrate Monotherapy | Changes in Serum Fasting Glucose Levels. | Adjusted End line serum fasting glucose | 91.7 mg/dl | Standard Error 2 |
| Fenofibrate Monotherapy | Changes in Serum Fasting Glucose Levels. | Baseline serum fasting glucose | 98.9 mg/dl | Standard Error 3.2 |
| WMER Niacin Monotherapy | Changes in Serum Fasting Glucose Levels. | Baseline serum fasting glucose | 94.6 mg/dl | Standard Error 3.3 |
| WMER Niacin Monotherapy | Changes in Serum Fasting Glucose Levels. | Adjusted End line serum fasting glucose | 100.1 mg/dl | Standard Error 2.1 |
| Combination Therapy | Changes in Serum Fasting Glucose Levels. | Baseline serum fasting glucose | 94.7 mg/dl | Standard Error 3.4 |
| Combination Therapy | Changes in Serum Fasting Glucose Levels. | Adjusted End line serum fasting glucose | 87.3 mg/dl | Standard Error 2.1 |
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline FSG level as a covariate.p-value: 0.001ANCOVA
Secondary
Changes in Serum Uric Acid Levels
Assessments involve the measurement of serum uric acid levels
Time frame: Changes from baseline were assessed at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Serum Uric Acid Levels | Baseline serum uric acid | 4.45 mg/dl | Standard Error 0.3 |
| Placebo | Changes in Serum Uric Acid Levels | Adjusted End line serum uric acid | 4.80 mg/dl | Standard Error 0.25 |
| Fenofibrate Monotherapy | Changes in Serum Uric Acid Levels | Adjusted End line serum uric acid | 4.0 mg/dl | Standard Error 0.22 |
| Fenofibrate Monotherapy | Changes in Serum Uric Acid Levels | Baseline serum uric acid | 5.21 mg/dl | Standard Error 0.24 |
| WMER Niacin Monotherapy | Changes in Serum Uric Acid Levels | Baseline serum uric acid | 4.87 mg/dl | Standard Error 0.25 |
| WMER Niacin Monotherapy | Changes in Serum Uric Acid Levels | Adjusted End line serum uric acid | 5.6 mg/dl | Standard Error 0.23 |
| Combination Therapy | Changes in Serum Uric Acid Levels | Baseline serum uric acid | 5.28 mg/dl | Standard Error 0.26 |
| Combination Therapy | Changes in Serum Uric Acid Levels | Adjusted End line serum uric acid | 3.9 mg/dl | Standard Error 0.24 |
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline serum uric acid level as a covariate.p-value: 0.0001ANCOVA
Secondary
Changes in Systolic and Diastolic Blood Pressure
Assessments involve the measurement of systolic and diastolic blood pressure. Patients were allowed to rest for 15 minutes in sitting position, and Walgreens Homedics WGNBPA-540 upper arm blood pressure monitor (Walgreens, China), was used for the measurement of blood pressure. Three consecutive readings were taken at 1 minute interval, and systolic and diastolic blood pressure were calculated as the mean of the last two readings.
Time frame: Changes from baseline were assessed at the end of the eighth week of treatments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Systolic and Diastolic Blood Pressure | Baseline diastolic blood pressure | 80.7 mmHg | Standard Error 2.6 |
| Placebo | Changes in Systolic and Diastolic Blood Pressure | Baseline systolic blood pressure | 120.7 mmHg | Standard Error 3.9 |
| Placebo | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line diastolic blood pressure | 79.5 mmHg | Standard Error 1 |
| Placebo | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line systolic blood pressure | 118.3 mmHg | Standard Error 2.1 |
| Fenofibrate Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Baseline systolic blood pressure | 125.4 mmHg | Standard Error 3.1 |
| Fenofibrate Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line diastolic blood pressure | 78.6 mmHg | Standard Error 0.9 |
| Fenofibrate Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line systolic blood pressure | 117.4 mmHg | Standard Error 1.8 |
| Fenofibrate Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Baseline diastolic blood pressure | 83.5 mmHg | Standard Error 2.1 |
| WMER Niacin Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line diastolic blood pressure | 80.3 mmHg | Standard Error 1.1 |
| WMER Niacin Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Baseline systolic blood pressure | 118.5 mmHg | Standard Error 3.4 |
| WMER Niacin Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line systolic blood pressure | 117.8 mmHg | Standard Error 2.2 |
| WMER Niacin Monotherapy | Changes in Systolic and Diastolic Blood Pressure | Baseline diastolic blood pressure | 76.1 mmHg | Standard Error 2.3 |
| Combination Therapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line systolic blood pressure | 118.8 mmHg | Standard Error 2.2 |
| Combination Therapy | Changes in Systolic and Diastolic Blood Pressure | Baseline systolic blood pressure | 119.5 mmHg | Standard Error 3.5 |
| Combination Therapy | Changes in Systolic and Diastolic Blood Pressure | Baseline diastolic blood pressure | 77.3 mmHg | Standard Error 2.4 |
| Combination Therapy | Changes in Systolic and Diastolic Blood Pressure | Adjusted End line diastolic blood pressure | 80.9 mmHg | Standard Error 1.1 |
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline diastolic blood pressure level as a covariate.p-value: 0.434ANCOVA
Comparison: Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline systolic blood pressure level as a covariate.p-value: 0.966ANCOVA