Trial Outcomes & Findings for Effect of MK0524A on Cholesterol Levels (0524A-048) (NCT NCT00536510)

Last Updated: 2015-09-02

Results Overview

Low Density Lipoprotein Cholesterol (LDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

646 participants

Primary outcome timeframe

12 weeks

Results posted on

2015-09-02

Participant Flow

Phase III First Patient In: 10-May-2007 Last Patient Last Visit: 11-Mar-2008 42 Outpatient centers in China (21), Hong Kong (2), India (11), and Korea (8)

Asia-regional lipid study with patients 18-70 yrs, including diabetic patients +/- statin, without ischemic vascular disease and LDL-C\<130 mg/dL (3.37 mmol/L), patients on a statin with ≥2 risk factors with LDL-C ≥130 and ≤160 mg/dL (3.37 and 4.14 mmol/L), and patients +/- statin with ≤1 risk factor with ≥130 and ≤190 mg/dL (3.37 and 4.92 mmol/L).

Participant milestones

Participant milestones
Measure	MK0524A 2 g All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Overall Study STARTED	322	324
Overall Study COMPLETED	240	295
Overall Study NOT COMPLETED	82	29

Reasons for withdrawal

Reasons for withdrawal
Measure	MK0524A 2 g All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Overall Study Adverse Event	27	4
Overall Study Lost to Follow-up	11	8
Overall Study Protocol Violation	4	5
Overall Study Withdrawal by Subject	16	9
Overall Study Flushing with Product	20	0
Overall Study Laboratory Adverse Event	2	1
Overall Study Patient Discontinued for Other Reasons	2	2

Baseline Characteristics

Effect of MK0524A on Cholesterol Levels (0524A-048)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK0524A 2 g n=322 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo n=324 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.	Total n=646 Participants Total of all reporting groups
Age, Customized <65 years	276 participants n=5 Participants	279 participants n=7 Participants	555 participants n=5 Participants
Age, Customized >=65 years	46 participants n=5 Participants	45 participants n=7 Participants	91 participants n=5 Participants
Sex: Female, Male Female	191 Participants n=5 Participants	185 Participants n=7 Participants	376 Participants n=5 Participants
Sex: Female, Male Male	131 Participants n=5 Participants	139 Participants n=7 Participants	270 Participants n=5 Participants
Concomitant Statin Use Yes	150 Participants n=5 Participants	146 Participants n=7 Participants	296 Participants n=5 Participants
Concomitant Statin Use No	172 Participants n=5 Participants	178 Participants n=7 Participants	350 Participants n=5 Participants
Country China (includes Hong Kong)	159 Participants n=5 Participants	158 Participants n=7 Participants	317 Participants n=5 Participants
Country India	82 Participants n=5 Participants	79 Participants n=7 Participants	161 Participants n=5 Participants
Country Korea	81 Participants n=5 Participants	87 Participants n=7 Participants	168 Participants n=5 Participants
Glycemic Status Normal*	166 Participants n=5 Participants	156 Participants n=7 Participants	322 Participants n=5 Participants
Glycemic Status Impaired Glucose*	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Glycemic Status Diabetic*	148 Participants n=5 Participants	164 Participants n=7 Participants	312 Participants n=5 Participants
High Density Lipoprotein Cholesterol (HDL-C)	48.1 mg/dL STANDARD_DEVIATION 10.8 • n=5 Participants	48.5 mg/dL STANDARD_DEVIATION 11.8 • n=7 Participants	48.3 mg/dL STANDARD_DEVIATION 11.3 • n=5 Participants
Low Density Lipoprotein Cholesterol (LDL-C)	124 mg/dL STANDARD_DEVIATION 34.4 • n=5 Participants	121.8 mg/dL STANDARD_DEVIATION 34.0 • n=7 Participants	122.9 mg/dL STANDARD_DEVIATION 34.2 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Full Analysis Set: consisted of all randomized patients who (i) took at least one dose of the treatment period study medication and (ii) had a baseline measurement and at least one measurement during Weeks 5 to 12. The last available lipid values during Weeks 5 to 12 were used for patients who had no lipid data collected at Week 12.

Low Density Lipoprotein Cholesterol (LDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100

Outcome measures

Outcome measures
Measure	MK0524A 2 g n=259 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo n=298 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) After 12 Weeks	-10.3 Percent Change Interval -13.2 to -7.4	4.4 Percent Change Interval 1.7 to 7.2

SECONDARY outcome

Timeframe: 12 weeks

Percent change from baseline in High Density Lipoprotein Cholesterol (HDL-C) after 12 weeks is calculated as the difference between week 12 measure and baseline measure divided by baseline measure \*100

Outcome measures

Outcome measures
Measure	MK0524A 2 g n=259 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo n=300 Participants All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) After 12 Weeks	18.6 Percent Change Interval 16.1 to 21.1	2.6 Percent Change Interval 0.3 to 5.0

Adverse Events

MK0524A 2 g

Serious events: 3 serious events

Other events: 123 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK0524A 2 g n=321 participants at risk All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo n=323 participants at risk All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Gastrointestinal disorders Duodenal Ulcer Haemorrhage	0.31% 1/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.00% 0/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Gastrointestinal disorders Gastric Ulcer	0.31% 1/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.00% 0/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Gastrointestinal disorders Gastritis Haemorrhagic	0.31% 1/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.00% 0/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.31% 1/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.31% 1/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Musculoskeletal and connective tissue disorders Periarthritis	0.31% 1/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.00% 0/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.

Other adverse events

Other adverse events
Measure	MK0524A 2 g n=321 participants at risk All patients received placebo for a 4 week run-in period before randomization. Drug: laropiprant/niacin (MK0524A) Treatment Period 1: one 20 mg /1 g tablet of laropiprant/niacin once daily for 4 weeks. Treatment Period 2: two 20 mg /1 g tablets of laropiprant/niacin once daily for 8 weeks.	Placebo n=323 participants at risk All patients received placebo for a 4 week run-in period before randomization. Drug: Comparator: placebo Treatment Period 1: one 20 mg /1 g tablet placebo to laropiprant/niacin once daily for 4 weeks Treatment Period 2: two 20 mg /1 g tablets of placebo to laropiprant/niacin once daily for 8 weeks.
Gastrointestinal disorders Nausea	3.1% 10/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	1.5% 5/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Infections and infestations Upper Respiratory Tract Infection	2.2% 7/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	3.1% 10/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Skin and subcutaneous tissue disorders Pruritus	8.1% 26/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.93% 3/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Skin and subcutaneous tissue disorders Rash	4.0% 13/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	0.62% 2/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Vascular disorders Flushing	11.5% 37/321 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	2.5% 8/323 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Endocrine disorders Alanine Aminotransferase Increased	3.0% 9/298 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	2.9% 9/310 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Endocrine disorders Creatine Phosphokinase Increased	4.0% 12/299 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	2.9% 9/310 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
General disorders Fasting Blood Glucose Increased	3.2% 9/281 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	2.3% 7/302 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.
Renal and urinary disorders Protein Urine Present	3.0% 1/33 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.	3.1% 1/32 The number of participants at risk for laboratory adverse events represents participants for whom laboratory test results were recorded postbaseline.

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 Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER