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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00289900
First received: February 7, 2006
Last updated: December 17, 2015
Last verified: December 2015
  Purpose
This is a 12-week clinical trial in participnats 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.

Condition Intervention Phase
Mixed Hyperlipidemia
Drug: MK-0524A
Drug: Atorvastatin
Drug: Simvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage Change From Baseline in the LDL-C/HDL-C Ratio [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage Change From Baseline in HDL-C [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Triglycerides (TG) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Non-HDL-C [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in LDL-C [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Apolipoprotein (Apo) B [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Apo A-I [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Lipoprotein (a) (Lp[a]) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in C-reactive Protein (CRP) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in TC/HDL-C Ratio [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN) [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Elevations in ALT and/or AST of >=10 x ULN [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Creatine Kinase (CK) >=10 x ULN [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With CK >=10 x ULN With Muscle Symptoms [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With New Diagnosis of Impaired Fasting Blood Glucose [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With New Diagnosis of Diabetes [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Experience at Least 1 Clinical Adverse Event (AE) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Experience at Least 1 Laboratory Adverse Event (AE) [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Were Discontinued From the Study Due to a Clinical AE [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Were Discontinued From the Study Due to a Laboratory AE [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Experience at Least 1 Hepatitis-related Clinical AE [ Time Frame: up to 14 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 2340
Study Start Date: January 2006
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: MK-0524A Drug: Simvastatin
Other Name: Zocor
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: MK-0524A Drug: Simvastatin
Other Name: Zocor
Active Comparator: Atorvastatin 10 mg
Atorvastatin 10 mg, orally, once daily for 12 weeks
Drug: Atorvastatin
Other Name: Lipitor
Active Comparator: Atorvastatin 20 mg
Atorvastatin 20 mg, orally, once daily for 12 weeks
Drug: Atorvastatin
Other Name: Lipitor
Active Comparator: Atorvastatin 40 mg
Atorvastatin 40 mg, orally, once daily for 12 weeks
Drug: Atorvastatin
Other Name: Lipitor
Active Comparator: Atorvastatin 80 mg
Atorvastatin 80 mg, orally, once daily for 12 weeks
Drug: Atorvastatin
Other Name: Lipitor

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00289900

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00289900     History of Changes
Other Study ID Numbers: 0524B-024  MK-0524B-024  2005_103 
Study First Received: February 7, 2006
Results First Received: December 17, 2015
Last Updated: December 17, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyperlipidemias
Hyperlipidemia, Familial Combined
Hyperlipoproteinemia Type V
Lipidoses
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Hypertriglyceridemia
Atorvastatin Calcium
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 24, 2016