A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118)

Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the LDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.

Time frame: Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III)

Population: Study was terminated by the Sponsor prior to completion. No planned efficacy summaries or analyses were completed.

Blood samples were taken at baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment (Week 12 for Period II and Week 20 for Period III) to determine the HDL-C levels. The change from baseline after 8 weeks of treatment was recorded. Results from recent studies indicated that the combination tablet formulations used in the study did not meet the pre-specified pharmacokinetic bounds used to establish the equivalence of the combination tablet (MK-0524B; ERN/LRPT/SIM) to the coadministration of MK-0524A (ERN/LRPT) and SIM. Therefore, efficacy data were not analyzed, as the study was stopped early. Only safety data were evaluated.

Time frame: Baseline (Week 4 for Period II; Week 12 for Period III) and after 8 weeks of treatment during each period (Week 12 for Period II and Week 20 for Period III)

Population: Study was terminated by the Sponsor prior to completion. No planned efficacy summaries or analyses were completed.

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.

Time frame: up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)

Population: All participants who received at least 1 dose of study drug. Safety analysis was based on the experiences accumulated during Periods I/II combined (pre-crossover), where the study followed a parallel design. A separate safety analysis was performed for Period III (post-crossover).

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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All participants who received at least 1 dose of study drug. Safety analysis was based on the experiences accumulated during Periods I/II combined (pre-crossover), where the study followed a parallel design. A separate safety analysis was performed for Period III (post-crossover).

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. Participants who were discontinued from the study due to an AE were recorded.

Time frame: up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)

Population: All participants who received at least 1 dose of study drug. Safety analysis was based on the experiences accumulated during Periods I/II combined (pre-crossover), where the study followed a parallel design. A separate safety analysis was performed for Period III (post-crossover).

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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All participants who received at least 1 dose of study drug. Safety analysis was based on the experiences accumulated during Periods I/II combined (pre-crossover), where the study followed a parallel design. A separate safety analysis was performed for Period III (post-crossover).

Participants had CK levels assessed throughout the treatment periods. 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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline measurement within 14 days of the last dose of study drug. Analysis was based on the experiences accumulated during Periods I/II combined, where the study followed a parallel design. A separate safety analysis was performed for Period III.

Participants had AST and ALT levels assessed during Period I (4 weeks ) and throughout each 8 week treatment period (20 weeks total). Participants who had an assessment of either AST or ALT that was 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.

Time frame: Up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline measurement within 14 days of the last dose of study drug. Analysis was based on the experiences accumulated during Periods I/II combined, where the study followed a parallel design. A separate safety analysis was performed for Period III.

Participants had CK levels assessed throughout the treatment periods. 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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline measurement within 14 days of the last dose of study drug. Analysis was based on the experiences accumulated during Periods I/II combined, where the study followed a parallel design. A separate safety analysis was performed for Period III.

Participants had AST and ALT levels assessed during Period I (4 weeks ) throughout each 8 week treatment period (20 weeks total). 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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline measurement within 14 days of the last dose of study drug. Analysis was based on the experiences accumulated during Periods I/II combined, where the study followed a parallel design. A separate safety analysis was performed for Period III.

Participants had AST and ALT levels assessed during Period I (4 weeks ) throughout each 8 week treatment period (20 weeks total). 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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline measurement within 14 days of the last dose of study drug. Analysis was based on the experiences accumulated during Periods I/II combined, where the study followed a parallel design. A separate safety analysis was performed for Period III.

Participants who with newly diagnosed of diabetes were recorded. A participant was classified as having new onset diabetes if they experienced an 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.

Time frame: up 20 weeks (12 weeks in Periods I/II and 8 weeks in Period III)

Population: All participants without diabetes at baseline and who received at least 1 dose of study drug. Safety analysis was based on the experiences accumulated during Periods I/II combined (pre-crossover), where the study followed a parallel design. A separate safety analysis was performed for Period III (post-crossover).