Lipid Efficacy and Safety in Participants With Mixed Hyperlipidemia (MK-0524B-024)

A Multicenter, Randomized, Double-Blind, Parallel Group, 12 Week Study to Evaluate the Efficacy and Safety of MK0524B Versus Atorvastatin in Patients With Mixed Hyperlipidemia

This is a 12-week clinical trial in participants with mixed hyperlipidemia to study the effects of MK-0524B on lipids.The primary hypothesis is that MK-0524B (dosed as MK-0524A coadministered with simvastatin) will be superior to atorvastatin on decreasing the low denisity lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio for the following dose comparisons: 2g/20 mg MK-0524B versus 10 mg atorvastatin, 2g/40 mg MK-0524B versus 20 mg atorvastatin, 2g/40 mg MK-0524B versus 40 mg atorvastatin, and 2g/40 mg MK-0524B versus 80 mg atorvastatin.

Study Overview

• Status: Completed
• Conditions: Mixed Hyperlipidemia
• Intervention / Treatment: Drug: Atorvastatin; Drug: Simvastatin; Drug: MK-0524A

• Study Type: Interventional
• Enrollment (Actual): 2340
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant 18 to 80 years of age with Mixed Hyperlipidemia with LDL-C between 130 and 190 mg/dL and Triglycerides between 150 and 500 mg/dL

Exclusion Criteria:

• Pregnant or lactating women, or women intending to become pregnant
• Diabetes mellitus that is poorly controlled, newly diagnosed, or taking new or recently adjusted antidiabetic therapy (with the exception of ± 10 units of insulin)
• Human immunodeficiency virus (HIV) positive
• Any of the following within the past 3 months: heart attack, stoke, heart bypass surgery, unstable angina, angioplasty
• Active or chronic liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-0524B 2g/20 mg; Co-administration of one tablet of MK-0524A (Extended Release [ER] niacin/laropiprant [LRPT] 1g + one tablet of simvastatin 10 mg for 4 weeks, then co-administration of two tablets of MK-0524A 1g + simvastatin 20 mg for 8 weeks	Drug: Simvastatin; Other Names: Zocor; Drug: MK-0524A
Experimental: MK-0524B 2g/40mg; Co-administration of one tablet of MK-0524A 1g + one tablet of simvastatin 20 mg for 4 weeks, then co-administration of two tablets of MK-0524A 1g + simvastatin 40 mg for 8 weeks	Drug: Simvastatin; Other Names: Zocor; Drug: MK-0524A
Active Comparator: Atorvastatin 10 mg; Atorvastatin 10 mg, orally, once daily for 12 weeks	Drug: Atorvastatin; Other Names: Lipitor
Active Comparator: Atorvastatin 20 mg; Atorvastatin 20 mg, orally, once daily for 12 weeks	Drug: Atorvastatin; Other Names: Lipitor
Active Comparator: Atorvastatin 40 mg; Atorvastatin 40 mg, orally, once daily for 12 weeks	Drug: Atorvastatin; Other Names: Lipitor
Active Comparator: Atorvastatin 80 mg; Atorvastatin 80 mg, orally, once daily for 12 weeks	Drug: Atorvastatin; Other Names: Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in the LDL-C/HDL-C Ratio	Blood samples taken at baseline and after 12 weeks of treatment to determine the LDL-C and HDL-C levels. The LDL-C/HDL-C ratio was then calculated for baseline and Week 12 and the change from baseline at Week 12 was recorded.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in HDL-C	Blood samples taken at baseline and after 12 weeks of treatment to determine the HDL-C levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Triglycerides (TG)	Blood samples taken at baseline and after 12 weeks of treatment to determine the TG levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Non-HDL-C	Blood samples taken at baseline and after 12 weeks of treatment to determine the non-HDL-C levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in LDL-C	Blood samples taken at baseline and after 12 weeks of treatment to determine the LDL-C levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Apolipoprotein (Apo) B	Blood samples taken at baseline and after 12 weeks of treatment to determine the Apo B levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Apo A-I	Blood samples taken at baseline and after 12 weeks of treatment to determine the Apo A-I levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Total Cholesterol (TC)	Blood samples taken at baseline and after 12 weeks of treatment to determine the TC levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in Lipoprotein (a) (Lp[a])	Blood samples taken at baseline and after 12 weeks of treatment to determine the Lp(a) levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in C-reactive Protein (CRP)	Blood samples taken at baseline and after 12 weeks of treatment to determine the CRP levels. The change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage Change From Baseline in TC/HDL-C Ratio	Blood samples taken at baseline and after 12 weeks of treatment to determine the TC and HDL-C levels. The TC/HDL-C ratio was then calculated for baseline and Week 12 and the change from baseline at Week 12 was recorded.	Baseline and Week 12
Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)	Participants had AST and ALT levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of either AST or ALT that were 3 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.	up to 12 weeks
Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN	Participants had AST and ALT levels assessed throughout the 12 week treatment period. Participants who had an assessment of either AST or ALT that was 5 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.	up to 12 weeks
Percentage of Participants With Elevations in ALT and/or AST of >=10 x ULN	Participants had AST and ALT levels assessed throughout the 12 week treatment period. Participants who had an assessment of either AST or ALT that was 10 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.	up to 12 weeks
Percentage of Participants With Creatine Kinase (CK) >=10 x ULN	Participants had CK assessed throughout the 12 week treatment period. Participants who had any CK level that was >=10 x ULN were recorded. The UNLs for males and females were 207 U/L and 169 U/L, respectively.	up to 12 weeks
Percentage of Participants With CK >=10 x ULN With Muscle Symptoms	Participants had CK assessed throughout the 24 week treatment period. Participants who had any CK level that was >=10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The UNLs for males and females were 207 U/L and 169 U/L, respectively.	up to 12 weeks
Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related	Participants had CK assessed throughout the 12 week treatment period. Participants who had any CK level that was >=10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly related to study drug were recorded. The UNLs for males and females were 207 U/L and 169 U/L, respectively.	up to 12 weeks
Percentage of Participants With New Diagnosis of Impaired Fasting Blood Glucose	Participants had blood glucose levels assessed throughout the 12 week treatment period. Participants who had the new diagnosis of impaired fasting blood glucose were recorded. A pre-defined set of MedDRA terms was used to identify participants whose glycemic status became 'impaired' during the course of treatment (from clinical adverse experience reports). The MedDRA terms were as follows: blood glucose increased, blood glucose abnormal, glucose tolerance decreased, glucose tolerance test abnormal, carbohydrate tolerance decreased, glucose tolerance impaired, hyperglycaemia, impaired fasting glucose, impaired insulin secretion, metabolic syndrome, insulin resistance, insulin resistance syndrome.	up to 12 weeks
Percentage of Participants With New Diagnosis of Diabetes	Participants had blood glucose levels assessed throughout the 12 week treatment period. Participants who with newly diagnosed of diabetes were recorded. A participant was classified as having new onset diabetes if they experienced an adverse Event (AE) related to a diagnosis of diabetes (based on a pre-defined set of Medical Dictionary for Regulatory Activities [MedDRA] terms), or if they started taking an anti-diabetic medication during the course of the study. The MedDRA terms were as follows: diabetes mellitus, diabetes mellitus insulin-dependent, diabetes mellitus non-insulin dependent, insulin-requiring type II diabetes mellitus, insulin resistant diabetes, diabetes with hyperosmolarity, latent autoimmune diabetes in adults.	up to 12 weeks
Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event	Select serious adverse cardiovascular events and all-cause mortality that occurred during the treatment phase of the study were adjudicated by an expert committee external to the sponsor. Those events confirmed by the committee a cardiovascular events were recorded.	up to 14 weeks
Percentage of Participants Who Experience at Least 1 Clinical Adverse Event (AE)	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A clinical AE was an AE reported as a result of a clinical examination or reported by the participant.	up to 14 weeks
Percentage of Participants Who Experience at Least 1 Laboratory Adverse Event (AE)	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test.	up to 14 weeks
Percentage of Participants Who Were Discontinued From the Study Due to a Clinical AE	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A clinical AE was an AE reported as a result of a clinical examination or reported by the participant. Participants who were discontinued from the study due to a clinical AE were recorded.	up to 14 weeks
Percentage of Participants Who Were Discontinued From the Study Due to a Laboratory AE	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test. Participants who were discontinued from the study due to a laboratory AE were recorded.	up to 14 weeks
Percentage of Participants Who Experience at Least 1 Hepatitis-related Clinical AE	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. Hepatitis-related AEs were identified by a collective review using the following pre-specified set of preferred terms: cholestasis, hepatic necrosis, hepatocellular damage, cytolytic hepatitis, hepatitis, hepatomegaly, jaundice, hepatic failure, hepatitis cholestatic, jaundice cholestatic, hepatitis fulminant, hyperbilirubinaemia, jaundice hepatocellular, ocular icterus, yellow skin, hepatic function abnormal, acute hepatic failure, subacute hepatic failure, hepatitis acute, hepatitis toxic, hepatotoxicity, and mixed hepatocellular-cholestatic injury.	up to 14 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Chen F, Maccubbin D, Yan L, Sirah W, Chen E, Sisk CM, Davidson M, Blomqvist P, McKenney JM. Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia. Int J Cardiol. 2013 Jul 15;167(1):225-31. doi: 10.1016/j.ijcard.2011.12.103. Epub 2012 Feb 4.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2006
• Primary Completion (Actual): August 6, 2010
• Study Completion (Actual): August 6, 2010

Study Registration Dates

• First Submitted: February 7, 2006
• First Submitted That Met QC Criteria: February 8, 2006
• First Posted (Estimate): February 10, 2006

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hypertriglyceridemia; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipidemia, Familial Combined; Lipidoses; Hyperlipoproteinemia Type V; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Simvastatin
• Other Study ID Numbers: 0524B-024; MK-0524B-024 (Other Identifier: Merck Study Number); 2005_103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis Link