Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118) (NCT NCT01294683)
NCT ID: NCT01294683
Last Updated: 2018-08-16
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
977 participants
Primary outcome timeframe
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)
Results posted on
2018-08-16
Participant Flow
Participants completed a 6-8 week washout then completed a 2-week placebo run-in prior to the start of active treatment.
Participant milestones
| Measure |
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release niacin/laropiprant (ERN/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
|
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
|
|---|---|---|
|
Precrossover (Periods I/II)
STARTED
|
489
|
488
|
|
Precrossover (Periods I/II)
Treated
|
486
|
486
|
|
Precrossover (Periods I/II)
COMPLETED
|
232
|
222
|
|
Precrossover (Periods I/II)
NOT COMPLETED
|
257
|
266
|
|
Post Crossover (Period III)
STARTED
|
232
|
222
|
|
Post Crossover (Period III)
COMPLETED
|
199
|
190
|
|
Post Crossover (Period III)
NOT COMPLETED
|
33
|
32
|
Reasons for withdrawal
| Measure |
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
After a 2-week placebo run-in, participants received extended release niacin/laropiprant (ERN/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
|
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
|
|---|---|---|
|
Precrossover (Periods I/II)
Adverse Event
|
49
|
52
|
|
Precrossover (Periods I/II)
Lost to Follow-up
|
3
|
6
|
|
Precrossover (Periods I/II)
Non-compliance with Study Drug
|
1
|
1
|
|
Precrossover (Periods I/II)
Physician Decision
|
1
|
0
|
|
Precrossover (Periods I/II)
Protocol Violation
|
5
|
5
|
|
Precrossover (Periods I/II)
Study Terminated by Sponsor
|
187
|
192
|
|
Precrossover (Periods I/II)
Technical Problems
|
0
|
1
|
|
Precrossover (Periods I/II)
Withdrawal by Subject
|
11
|
9
|
|
Post Crossover (Period III)
Adverse Event
|
6
|
6
|
|
Post Crossover (Period III)
Lost to Follow-up
|
1
|
3
|
|
Post Crossover (Period III)
Study Terminated by Sponsor
|
23
|
21
|
|
Post Crossover (Period III)
Withdrawal by Subject
|
3
|
2
|
Baseline Characteristics
A Study to Evaluate Efficacy and Safety of Extended-Release Niacin + Laropiprant + Simvastatin in Participants With Primary Hypercholesterolemia or Mixed Dyslipidemia (MK-0524B-118)
Baseline characteristics by cohort
| Measure |
Sequence 1: MK-0524B 2g/40g→MK-0524A 2g + Simvastatin 40 mg
n=489 Participants
After a 2-week placebo run-in, participants received extended release niacin/laropiprant (ERN/LRPT) 1 g/20 mg combination tablet (MK-0524B) once daily for 4 weeks, then ERN/LRPT/Simvastatin (SIM) 2 g/40 mg combination tablet once daily for 8 weeks. Participants then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks.
|
Sequence 2: MK-0524A 2g + Simvastatin 40 mg→ MK-0524B 2g/40g
n=488 Participants
After a 2-week placebo run-in, participants received ERN/LRPT 1 g (MK-0524A) co-administered with SIM 20 mg once daily for 4 weeks then received ERN/LRPT 2 g (MK-0524A) co-administered with SIM 40 mg once daily for 8 weeks. Participants then received ERN/LRPT/SIM 2 g/40 mg combination tablets (MK-0524B) once daily for 8 weeks.
|
Total
n=977 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.9 years
STANDARD_DEVIATION 10.2 • n=93 Participants
|
57.9 years
STANDARD_DEVIATION 10.2 • n=4 Participants
|
56.9 years
STANDARD_DEVIATION 10.3 • n=27 Participants
|
|
Sex: Female, Male
Female
|
230 Participants
n=93 Participants
|
258 Participants
n=4 Participants
|
488 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
259 Participants
n=93 Participants
|
230 Participants
n=4 Participants
|
489 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 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 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x Upper Limit of Normal (ULN)
|
0.4 Percentage of Participants
|
0.6 Percentage of Participants
|
1.3 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With Elevations in ALT and/or AST of >=5 x ULN
|
0.2 Percentage of Participants
|
0.4 Percentage of Participants
|
0.9 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With Elevations in ALT and/or AST of >=10 x ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With Creatine Kinase (CK) >=10 x ULN
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.9 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With CK >=10 x ULN With Muscle Symptoms - Drug Related
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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. 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least 1 Hepatitis-related Adverse Event (AE)
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With New Onset of Diabetes
|
1.0 Percentage of Participants
|
0.4 Percentage of Participants
|
1.3 Percentage of Participants
|
0.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants With a Confirmed Adjudicated Cardiovascular Event
|
0.2 Percentage of Participants
|
0.2 Percentage of Participants
|
0.0 Percentage of Participants
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants Who Experienced at Least 1 AE
|
50.2 Percentage of Participants
|
51.2 Percentage of Participants
|
30.4 Percentage of Participants
|
29.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: 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. Participants who were discontinued from the study due to an AE were recorded.
Outcome measures
| Measure |
MK-0524B 2g/40mg
n=486 Participants
Participants who received MK-0524B 2g/40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
MK-0524A 2g + Simvastatin 40 mg
n=486 Participants
Participants who received MK-0524A 2g+Simvastatin 40mg for 8 weeks in either Period II or Period III regardless of randomly assigned sequence.
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 Participants
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III.
|
Sequence 2: MK-0524B 2g/40g
n=220 Participants
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Discontinued From the Study Due to an AE
|
10.1 Percentage of Participants
|
10.5 Percentage of Participants
|
2.2 Percentage of Participants
|
2.7 Percentage of Participants
|
Adverse Events
Sequence 1: MK-0524B 2g/40g
Serious events: 6 serious events
Other events: 110 other events
Deaths: 0 deaths
Sequence 2: MK-0524A 2g + Simvastatin 40 mg
Serious events: 9 serious events
Other events: 98 other events
Deaths: 0 deaths
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Sequence 2: MK-0524B 2g/40g
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sequence 1: MK-0524B 2g/40g
n=486 participants at risk
Participants who received MK-0524B 1g/40mg and MK-0524B 2g/40mg during Periods I/II
|
Sequence 2: MK-0524A 2g + Simvastatin 40 mg
n=486 participants at risk
Participants who received MK-0524A 1g + Simvastatin 40mg and MK-0524A 2g+ Simvastatin 40mg during Periods I/II
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 participants at risk
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III
|
Sequence 2: MK-0524B 2g/40g
n=220 participants at risk
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Skin injury
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.45%
1/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Nervous system disorders
Syncope
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.43%
1/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Cardiac disorders
Acute myocardial infarction
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Cardiac disorders
Atrial fibrillation
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Cardiac disorders
Cardiac failure congestive
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
General disorders
Chest pain
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Nervous system disorders
Carotid artery disease
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Nervous system disorders
Hypoaesthesia
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Psychiatric disorders
Depression
|
0.00%
0/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.21%
1/486 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
Other adverse events
| Measure |
Sequence 1: MK-0524B 2g/40g
n=486 participants at risk
Participants who received MK-0524B 1g/40mg and MK-0524B 2g/40mg during Periods I/II
|
Sequence 2: MK-0524A 2g + Simvastatin 40 mg
n=486 participants at risk
Participants who received MK-0524A 1g + Simvastatin 40mg and MK-0524A 2g+ Simvastatin 40mg during Periods I/II
|
Sequence 1: MK-0524A 2g + Simvastatin 40 mg
n=230 participants at risk
Participants who received MK-0524A 2g+ Simvastatin 40mg during Period III
|
Sequence 2: MK-0524B 2g/40g
n=220 participants at risk
Participants who received MK-0524B 2g/40mg during Period III
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.6%
42/486 • Number of events 51 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
6.8%
33/486 • Number of events 38 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
|
Vascular disorders
Flushing
|
18.1%
88/486 • Number of events 104 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
15.4%
75/486 • Number of events 86 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/230 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
0.00%
0/220 • up 22 weeks (12 weeks in Periods I/II and 10 weeks in Period III)
Population included 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 follows a parallel design. A separate safety analysis was performed for Period III (post-crossover).
|
Additional Information
Senior Vice President, Global Clinical Development
Merck, Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER