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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Mixed Hyperlipidemia

Intervention / Treatment
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* Drug: MK-0524A
* Drug: Atorvastatin
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0524B 2g/20 mg<br>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: MK-0524A<br> <br> Drug: Simvastatin<br> <br> * Other names: Zocor;|
| Experimental: MK-0524B 2g/40mg<br>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: MK-0524A<br> <br> Drug: Simvastatin<br> <br> * Other names: Zocor;|
| Active Comparator: Atorvastatin 10 mg<br>Atorvastatin 10 mg, orally, once daily for 12 weeks | Drug: Atorvastatin<br> <br> * Other names: Lipitor;|
| Active Comparator: Atorvastatin 20 mg<br>Atorvastatin 20 mg, orally, once daily for 12 weeks | Drug: Atorvastatin<br> <br> * Other names: Lipitor;|
| Active Comparator: Atorvastatin 40 mg<br>Atorvastatin 40 mg, orally, once daily for 12 weeks | Drug: Atorvastatin<br> <br> * Other names: Lipitor;|
| Active Comparator: Atorvastatin 80 mg<br>Atorvastatin 80 mg, orally, once daily for 12 weeks | Drug: Atorvastatin<br> <br> * Other names: Lipitor;|

What is the study measuring?
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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 |