Extended Release Niacin and Fenofibrate for the Treatment of Atherogenic Dyslipidemia in Obese Females
Sponsor
Lewai Sharki Abdulaziz, MSc PhD (Other)
Overall Status
Completed
CT.gov ID
NCT03615534
Collaborator
Al-Kindy College of Medicine (Other)
161
2
4
12.9
80.5
6.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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:
-
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.
-
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:
-
Adverse events including flushing, nausea, vomiting, muscle pain, or dizziness turn sever enough to surpass patient's tolerability.
-
Estimated glomerular filtration rate (eGFR) is reduced to ˂ 60ml/min per 1.73 m2 indicating renal insufficiency.
-
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.
-
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
161 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Extended Release Niacin-Fenofibrate Combination and Monotherapy for the Treatment of Atherogenic Dyslipidemia in Obese Females
Actual Study Start Date
:
Oct 1, 2014
Actual Primary Completion Date
:
Jun 30, 2015
Actual Study Completion Date
:
Oct 30, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: 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. |
Other: Therapeutic Lifestyle Changes
Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Other: Placebo
|
| Active Comparator: 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. |
Other: Therapeutic Lifestyle Changes
Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Drug: Fenofibrate
Other Names:
|
| Active Comparator: 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. |
Other: Therapeutic Lifestyle Changes
Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Dietary Supplement: Wax Matrix Extended Release Niacin (WMER Niacin)
Other Names:
|
| Active Comparator: 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. |
Other: Therapeutic Lifestyle Changes
Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Drug: Fenofibrate
Other Names:
Dietary Supplement: Wax Matrix Extended Release Niacin (WMER Niacin)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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
- 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 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 60 Years
Sexes Eligible for Study:
Female
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Al Kindy College of Medicine, University of Baghdad | Baghdad | Iraq | 10045 | |
| 2 | Lewai S Abdulaziz | Baghdad | Iraq | 10045 |
Sponsors and Collaborators
- Lewai Sharki Abdulaziz, MSc PhD
- Al-Kindy College of Medicine
Investigators
- Study Chair: Lewai S Abdulaziz, MSc PhD, Al-Kindy college of Medicine, University of Baghdad
- Study Chair: May S Al-Sabbagh, MSc, College of Pharmacy, University of Baghdad
- Study Director: Marwah S Attar, MSc, College of Pharmacy, University of Baghdad
- Principal Investigator: Faris A Khazaal, FRCP, Al-Kindy college of Medicine, University of Baghdad
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Lewai Sharki Abdulaziz, MSc PhD,
Assistant Professor,
Al-Kindy College of Medicine
ClinicalTrials.gov Identifier:
NCT03615534
Other Study ID Numbers:
- 1Al-KindyCM
First Posted:
Aug 6, 2018
Last Update Posted:
Sep 4, 2019
Last Verified:
Apr 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Lewai Sharki Abdulaziz, MSc PhD,
Assistant Professor,
Al-Kindy College of Medicine
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Period Title: Overall Study | ||||
| STARTED | 14 | 15 | 14 | 14 |
| COMPLETED | 12 | 15 | 14 | 13 |
| NOT COMPLETED | 2 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) | Total of all reporting groups |
| Overall Participants | 12 | 15 | 14 | 13 | 54 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
36.2
(2.5)
|
37.3
(2.0)
|
36.6
(2.1)
|
40.2
(2.2)
|
37.6
(2.2)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
12
100%
|
15
100%
|
14
100%
|
13
100%
|
54
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg/m^2] |
38.9
(2.1)
|
41.5
(1.7)
|
42.0
(1.7)
|
39.7
(1.8)
|
40.6
(1.8)
|
Outcome Measures
| Title | Changes Serum Triglyceride Levels |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline TG levels |
223.1
(23.4)
|
241.2
(19.1)
|
227.0
(19.7)
|
267.2
(20.5)
|
| Adjusted End line TG levels |
220.2
(12.8)
|
133.7
(11.4)
|
164.0
(11.4)
|
136.1
(12.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | Results were evaluated in terms of adjusted end line TG levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: TG= 240.4 mg/dl, HDL-C = 31.8 mg/dl, ApoA1 = 144.6 mg/dl. | |
| Title | Changes in Serum Lipoprotein Cholesterol Levels |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline TC |
203.1
(11.4)
|
190.7
(9.3)
|
189.1
(9.6)
|
219.5
(10.0)
|
| Baseline HDL-C |
30.9
(2.1)
|
32.1
(1.7)
|
34.2
(1.8)
|
29.7
(1.8)
|
| Baseline d-LDL-C |
120.0
(7.5)
|
108.9
(6.2)
|
120.1
(6.4)
|
129.3
(6.6)
|
| Baseline non HDL-C |
172.3
(11.3)
|
158.6
(9.2)
|
154.9
(9.5)
|
189.7
(9.9)
|
| Baseline RC |
52.3
(8.4)
|
49.7
(6.8)
|
34.9
(7.1)
|
60.5
(7.3)
|
| Adjusted End line TC |
198.4
(7.4)
|
171.1
(6.7)
|
177.3
(6.6)
|
179.9
(6.4)
|
| Adjusted End line HDL-C |
32.0
(1.4)
|
37.2
(1.3)
|
38.3
(1.3)
|
42.8
(1.3)
|
| Adjusted End line d-LDL-C |
115.7
(6.6)
|
103.6
(5.9)
|
103.3
(5.9)
|
115.0
(6.2)
|
| Adjusted End line non HDL-C |
166.4
(7.7)
|
134.1
(6.9)
|
138.7
(6.9)
|
136.3
(7.2)
|
| Adjusted End line RC |
50.7
(4.8)
|
30.3
(4.3)
|
35.7
(4.3)
|
22.1
(4.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.060 |
| Comments | Results were evaluated in terms of adjusted end line TC levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: TC=199.9 mg/dl, Non HDL-C= 168.0 mg/dl, d-LDL-C= 119.1 mg/dl. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | Results were evaluated in terms of adjusted end line HDL-C levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: HDL-C = 31.8 mg/dL,TG= 240.4 mg/dL, ApoA1 = 144.6 mg/dL. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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 . | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.334 |
| Comments | Results were evaluated in terms of adjusted end line d-LDL-C levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: d-LDL-C= 119.1 mg/dl.TC=199.9 mg/dl, Non HDL-C= 168.0 mg/dl, | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | Results were evaluated in terms of adjusted end line Non HDL-C levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: Non HDL-C= 168.0 mg/dl,TC=199.9 mg/dl, d-LDL-C= 119.1 mg/dl. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | Results were evaluated in terms of adjusted end line RC levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values:RC=48.9,TC=199.9, Non HDL-C=168.0, d-LDL-C=119.1, ApoB=133.1mg/dl | |
| Title | Changes in Serum Apolipoprotein Levels |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline Apo A1 |
130.8
(8.7)
|
143.8
(7.1)
|
150.1
(7.4)
|
150.0
(7.7)
|
| Baseline Apo B |
134.1
(7.5)
|
141.8
(6.1)
|
123.0
(6.3)
|
133.1
(6.6)
|
| Adjusted End line Apo A1 |
130.2
(10.4)
|
155.9
(9.3)
|
134.2
(9.3)
|
162.3
(9.7)
|
| Adjusted End line Apo B |
124.7
(6.4)
|
106.7
(5.7)
|
111.1
(5.7)
|
101.7
(6.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.058 |
| Comments | Results were evaluated in terms of adjusted end line ApoA1 levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values: ApoA1 = 144.6 mg/dl, TG= 240.4 mg/dl, HDL-C = 31.8 mg/dl. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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 . | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.067 |
| Comments | Results were evaluated in terms of adjusted end line ApoB levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | MANCOVA | |
| Comments | Covariates appearing in MANCOVA model are evaluated at the following baseline values:ApoB=133.1, RC=48.9,TC=199.9, Non HDL-C=168.0, d-LDL-C=119.1mg/dl | |
| Title | Changes in Serum Fasting Glucose Levels. |
|---|---|
| Description | Assessments involve the measurement of serum fasting glucose levels. |
| Time Frame | Changes from baseline were assessed at the end eighth week of treatments. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline serum fasting glucose |
93.5
(3.9)
|
98.9
(3.2)
|
94.6
(3.3)
|
94.7
(3.4)
|
| Adjusted End line serum fasting glucose |
91.3
(2.3)
|
91.7
(2.0)
|
100.1
(2.1)
|
87.3
(2.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline FSG level as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | Results were evaluated in terms of adjusted end line FSG levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: FSG= 95.7 mg/dl. | |
| Title | Changes in Estimated Glomerular Filtration Rate (eGFR) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline eGFR |
89.8
(4.8)
|
86.5
(3.9)
|
91.0
(4.1)
|
85.2
(4.2)
|
| Adjusted End line eGFR |
83.1
(3.4)
|
83.2
(3.1)
|
82.9
(3.2)
|
79.2
(3.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline eGFR level as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.786 |
| Comments | Results were evaluated in terms of adjusted end line eGFR levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: eGFR= 88.0 ml/min per 1.73 m^2. | |
| Title | Changes in Serum Uric Acid Levels |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline serum uric acid |
4.45
(0.30)
|
5.21
(0.24)
|
4.87
(0.25)
|
5.28
(0.26)
|
| Adjusted End line serum uric acid |
4.80
(0.25)
|
4.0
(0.22)
|
5.6
(0.23)
|
3.9
(0.24)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | Results were evaluated in terms of adjusted end line serum uric acid levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: serum uric acid= 5.0 mg/dl. | |
| Title | Changes in Serum Enzymes Levels |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline AST |
17.1
(1.6)
|
18.8
(1.3)
|
17.0
(1.4)
|
18.9
(1.4)
|
| Baseline ALT |
13.1
(1.4)
|
16.3
(1.2)
|
16.0
(1.2)
|
17.8
(1.2)
|
| Baseline CK |
28.0
(4.7)
|
29.1
(3.8)
|
26.9
(4.0)
|
28.0
(4.1)
|
| Adjusted End line AST |
18.9
(0.8)
|
17.3
(0.8)
|
18.0
(0.8)
|
19.6
(0.8)
|
| Adjusted End line ALT |
15.4
(0.6)
|
14.4
(0.5)
|
16.4
(0.5)
|
16.2
(0.6)
|
| Adjusted End line CK |
27.3
(4.7)
|
34.9
(4.2)
|
27.4
(4.4)
|
28.2
(4.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline AST level as a covariate. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.201 |
| Comments | Results were evaluated in terms of adjusted end line AST levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: AST= 18.1 IU/L. . | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline ALT level as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | Results were evaluated in terms of adjusted end line ALT levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: ALT= 16.0 IU/L. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | Analysis of Covariance (ANCOVA), was applied to assess treatment effects among different arms, comprising the influence of the baseline CK level as a covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.511 |
| Comments | Results were evaluated in terms of adjusted end line CK levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: CK= 28.0 IU/L. | |
| Title | Changes in Systolic and Diastolic Blood Pressure |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Baseline diastolic blood pressure |
80.7
(2.6)
|
83.5
(2.1)
|
76.1
(2.3)
|
77.3
(2.4)
|
| Baseline systolic blood pressure |
120.7
(3.9)
|
125.4
(3.1)
|
118.5
(3.4)
|
119.5
(3.5)
|
| Adjusted End line diastolic blood pressure |
79.5
(1.0)
|
78.6
(0.9)
|
80.3
(1.1)
|
80.9
(1.1)
|
| Adjusted End line systolic blood pressure |
118.3
(2.1)
|
117.4
(1.8)
|
117.8
(2.2)
|
118.8
(2.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.434 |
| Comments | Results were evaluated in terms of adjusted end line diastolic blood pressure levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: diastolic blood pressure= 80.0 mmHg. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fenofibrate Monotherapy, WMER Niacin Monotherapy, Combination Therapy |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | Results were evaluated in terms of adjusted end line systolic blood pressure levels, embracing the least significant difference (LSD) for pair-wise comparison. Probability of less than 0.05 was considered statistically significant. | |
| Method | ANCOVA | |
| Comments | Covariates appearing in ANCOVA model are evaluated at the following baseline values: systolic blood pressure= 121.5 mmHg. | |
| Title | Adverse Events |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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) | 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) |
| Measure Participants | 12 | 15 | 14 | 13 |
| Muscle Pain |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
| Flushing |
0
0%
|
0
0%
|
1
7.1%
|
0
0%
|
| Nausea/Vomiting |
0
0%
|
0
0%
|
3
21.4%
|
1
7.7%
|
| Dizziness |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
Adverse Events
| Time Frame | Up to the end of the eighth week of treatments. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | ||||
| Arm/Group Description | 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 | 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 | 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) | 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) | ||||
All Cause Mortality |
||||||||
| Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 0/13 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 0/13 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Fenofibrate Monotherapy | WMER Niacin Monotherapy | Combination Therapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/15 (0%) | 7/14 (50%) | 3/13 (23.1%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea/Vomiting | 0/12 (0%) | 0/15 (0%) | 3/14 (21.4%) | 1/13 (7.7%) | ||||
| General disorders | ||||||||
| Flushing | 0/12 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/13 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| ALT or AST >3ULN | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 0/13 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Uric acid > 6 mg/dl | 0/12 (0%) | 0/15 (0%) | 3/14 (21.4%) | 0/13 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle Pain | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 1/13 (7.7%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 1/13 (7.7%) | ||||
| Renal and urinary disorders | ||||||||
| eGFR˂ 60ml/min per 1.73 m^2 | 0/12 (0%) | 0/15 (0%) | 0/14 (0%) | 0/13 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Lewai Sharki Abdulaziz |
|---|---|
| Organization | Al-Kindy College of Medicine, ////university of Baghdad |
| Phone | 750 659 0024 ext +964 |
| lewaisharki@kmc.uobaghdad.edu.iq |
Responsible Party:
Lewai Sharki Abdulaziz, MSc PhD,
Assistant Professor,
Al-Kindy College of Medicine
ClinicalTrials.gov Identifier:
NCT03615534
Other Study ID Numbers:
- 1Al-KindyCM
First Posted:
Aug 6, 2018
Last Update Posted:
Sep 4, 2019
Last Verified:
Apr 1, 2019