NCT03615534

Extended Release Niacin and Fenofibrate for the Treatment of Atherogenic Dyslipidemia in Obese Females

Efficacy and Safety of Extended Release Niacin-Fenofibrate Combination and Monotherapy for the Treatment of Atherogenic Dyslipidemia in Obese Females

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 161 (actual)
• Sponsor: Lewai Sharki Abdulaziz, MSc PhD · Academic / Other
• Sex: Female
• Age: 20 Years – 60 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Atherogenic Dyslipidemia
• Obesity Associated Disorder

Interventions

Type	Name	Description
OTHER	Therapeutic Lifestyle Changes	Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
OTHER	Placebo
DRUG	Fenofibrate
DIETARY_SUPPLEMENT	Wax Matrix Extended Release Niacin (WMER Niacin)

Timeline

• Start date: 2014-10-01
• Primary completion: 2015-06-30
• Completion: 2015-10-30
• First posted: 2018-08-06
• Last updated: 2024-01-24
• Results posted: 2018-10-12

Locations

2 sites across 1 country: Iraq

Regulatory

• FDA-regulated drug study