Extended Niacin/Laropiprant in Patients With Type 2 Diabetes (0524A-069)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00485758
• Collaborator: (none)
• Enrollment: 796
• Arms: 2
• Duration (Months): 13

Study Details

Study Description

Brief Summary

A study to assess the efficacy and tolerability of ER (Extended Release) niacin/laropiprant versus placebo in Type 2 Diabetes Mellitus patients.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2	Drug: ER niacin/laropiprant; Drug: Comparator : placebo (unspecified)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 796 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo Controlled 36 Week Study to Evaluate the Efficacy and Safety of Extended Release (ER) Niacin/Laropiprant in Patients With Type 2 Diabetes
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 Arm 1: One tablet of ER niacin/ laropiprant (1g) + one tablet of the run-in statin dose, advancing to ER niacin/laropiprant (2g) at Week 4 for the remainder of the study.	Drug: ER niacin/laropiprant; One tablet of ER niacin/laropiprant (1g); advancing to ER niacin/laropiprant (2g) at Week 4 for the remainder of the study 36 Weeks.; Other Names: MK0524A CORDAPTIVE™ laropiprant (+) niacin
Active Comparator: 2 Arm 2: stable lipid-modifying regimen, adding Placebo ER niacin/laropiprant in week 4, for the duration of the study.	Drug: Comparator : placebo (unspecified); ER niacin/laropiprant Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Low-density Lipoprotein Cholesterol in Patients With Type 2 Diabetes When Compared to Placebo [Baseline and 12 Weeks]

   After 12 Weeks of treatment, to assess the reduction of low-density lipoprotein cholesterol in patients with Type 2 diabetes when compared to placebo

Secondary Outcome Measures

1. Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in High Density Lipoprotein Cholesterol in Patients With Type 2 Diabetes When Compared to Placebo [Baseline and 12 Weeks]

   After 12 weeks of treatment, to assess the increase of high-density lipoprotein cholesterol in patients with Type 2 diabetes when compared to placebo

2. Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Triglycerides in Patients With Type 2 Diabetes When Compared to Placebo [Baseline and 12 Weeks]

   after 12 weeks of treatment, to assess the reduction of triglycerides in patients with Type 2 diabetes when compared to placebo

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients between the ages of 18 to 80 years with Type 2 Diabetes who are on a stable dose of antidiabetic medication for at least 3 months

Exclusion Criteria:

• Patients taking Cholestin, niacin (>50 mg/day), fibrate therapy, hormonal contraceptives, intermittent Hormone Replacement Therapy, or certain corticosteroids

• Patients with any of the following conditions: active liver disease or kidney disease, poorly controlled high blood pressure, active peptic ulcer, or other heart or blood diseases

• Patients with abnormal laboratory results from a blood test that will be given before starting the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00485758
• Other Study ID Numbers: 0524A-069; MK0524A-069; 2007_543
• First Posted: Jun 13, 2007
• Last Update Posted: Oct 12, 2015
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Niacin; Niacinamide; Nicotinic Acids

Study Results

Participant Flow

Recruitment Details	First Patient In:13-Aug-2007, Last Patient Last Visit:15-Jan-2009 Ninety-four (94) sites participated: Australia 2 sites; Belgium 7 sites; Canada 6 sites; Ecuador 2 sites; Finland 2 sites; Germany 8 sites; Israel 4 sites; Italy 3 sites; Malaysia 5 sites; New Zealand 4 sites; Portugal 4 sites; Sweden 10 sites; Taiwan 5 sites; United States 32 sites
Pre-assignment Detail	Patients with Type 2 Diabetes who were not at protocol specified low-density lipoprotein cholesterol goal of <115 milligrams/deciliter at screening, had a 4-week run-in period of lipid modifying therapy. In order to advance to randomization, patients had to meet the low-density lipoprotein cholesterol goal.

Arm/Group Title	Extended Release Niacin/Laropiprant	Placebo
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.	Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Period Title: Overall Study
STARTED	454	342
COMPLETED	298	277
NOT COMPLETED	156	65

Baseline Characteristics

Arm/Group Title	Extended Release Niacin/Laropiprant	Placebo	Total
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.	Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.	Total of all reporting groups
Overall Participants	454	342	796
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.0 (9.3)	62.0 (9.4)	62.0 (9.3)
Sex: Female, Male (Count of Participants)
Female	188 41.4%	126 36.8%	314 39.4%
Male	266 58.6%	216 63.2%	482 60.6%
Fasting Plasma Glucose (milligrams/deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams/deciliter]	132.0 (33.9)	133.6 (32.4)	132.7 (33.3)
High-density lipoprotein cholesterol (milligrams/deciliter (mg/dl)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams/deciliter (mg/dl)]	49.93 (13.49)	50.26 (13.23)	50.07 (13.37)
Low-density lipoprotein cholesterol (milligrams/deciliter (mg/dl)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams/deciliter (mg/dl)]	87.19 (20.54)	85.22 (18.00)	86.34 (19.50)
Triglycerides (milligrams/deciliter (mg/dl)) [Median (Full Range) ]
Median (Full Range) [milligrams/deciliter (mg/dl)]	126.00	129.00	127.00

Outcome Measures

1. Primary Outcome

Title	Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Low-density Lipoprotein Cholesterol in Patients With Type 2 Diabetes When Compared to Placebo
Description	After 12 Weeks of treatment, to assess the reduction of low-density lipoprotein cholesterol in patients with Type 2 diabetes when compared to placebo
Time Frame	Baseline and 12 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Extended Release Niacin/Laropiprant	Placebo
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.	Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Measure Participants	432	336
Least Squares Mean (95% Confidence Interval) [Percent change at Wk 12 compared to Bl]	-15.8	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended Release Niacin/Laropiprant, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Study times: 4, 8 and 12 weeks. Terms: treatment-by-time, gender-by-time and baseline low-density lipoprotein cholesterol -by-time interaction.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-17.9
	Confidence Interval	() 95%; -21.4 to -14.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

2. Secondary Outcome

Title	Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in High Density Lipoprotein Cholesterol in Patients With Type 2 Diabetes When Compared to Placebo
Description	After 12 weeks of treatment, to assess the increase of high-density lipoprotein cholesterol in patients with Type 2 diabetes when compared to placebo
Time Frame	Baseline and 12 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Extended Release Niacin/Laropiprant	Placebo
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.	Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Measure Participants	432	336
Least Squares Mean (95% Confidence Interval) [Percent change at Wk 12 compared to Bl]	25.4	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended Release Niacin/Laropiprant, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Analysis
	Comments	Study times: 4, 8 and 12 weeks. Terms: treatment-by-time, gender-by-time and baseline high-density lipoprotein cholesterol -by-time interaction.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	23.2
	Confidence Interval	() 95%; 20.7 to 25.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments

3. Secondary Outcome

Title	Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Triglycerides in Patients With Type 2 Diabetes When Compared to Placebo
Description	after 12 weeks of treatment, to assess the reduction of triglycerides in patients with Type 2 diabetes when compared to placebo
Time Frame	Baseline and 12 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set With at Least one Post-Titration Visit Measurement

Arm/Group Title	Extended Release Niacin/Laropiprant	Placebo
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.	Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Measure Participants	400	328
Median (95% Confidence Interval) [Percent change at Wk 12 compared to Bl]	-22.2	2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended Release Niacin/Laropiprant, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Nonparametric Analysis of Covariance model based on Tukey's normalized ranks with term for treatment, gender and Tukey's normal score of baseline.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-23.1
	Confidence Interval	() 95%; -27.2 to -18.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	The median difference between treatments is based on the Hodges-Lehmann estimates of shift with a corresponding distribution-free Confidence Interval based on Wilcoxon's rank

Adverse Events

Adverse Event Reporting Description	7 randomized patients took no study drug dose and were not included in the safety follow-up
Arm/Group Title	Extended Release Niacin/Laropiprant		Placebo
Arm/Group Description	One tablet of Extended Release Niacin/Laropiprant (1 gram/20 milligram) in addition to lipid modifying therapy. After 4 weeks, advanced to Extended Release Niacin/Laropiprant (2 gram/40 milligram). No adjustments were made to any lipid modifying regimen established during run-in until Week 12.		Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
All Cause Mortality
	Extended Release Niacin/Laropiprant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Extended Release Niacin/Laropiprant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/449 (5.8%)		24/340 (7.1%)
Blood and lymphatic system disorders
Anaemia	0/449 (0%)		1/340 (0.3%)
Cardiac disorders
Angina pectoris	0/449 (0%)		1/340 (0.3%)
Angina unstable	0/449 (0%)		2/340 (0.6%)
Aortic valve stenosis	1/449 (0.2%)		0/340 (0%)
Coronary artery disease	1/449 (0.2%)		2/340 (0.6%)
Myocardial infarction	2/449 (0.4%)		0/340 (0%)
Eye disorders
Cataract	1/449 (0.2%)		0/340 (0%)
Gastrointestinal disorders
Abdominal hernia	0/449 (0%)		1/340 (0.3%)
Diverticulum	1/449 (0.2%)		0/340 (0%)
Gastric ulcer	1/449 (0.2%)		0/340 (0%)
Gastrooesophageal reflux disease	0/449 (0%)		1/340 (0.3%)
Haematochezia	0/449 (0%)		1/340 (0.3%)
Mechanical ileus	1/449 (0.2%)		0/340 (0%)
Pancreatitis	0/449 (0%)		1/340 (0.3%)
Upper gastrointestinal haemorrhage	0/449 (0%)		1/340 (0.3%)
General disorders
Chest pain	0/449 (0%)		1/340 (0.3%)
Non-cardiac chest pain	1/449 (0.2%)		2/340 (0.6%)
Hepatobiliary disorders
Cholecystitis	1/449 (0.2%)		0/340 (0%)
Infections and infestations
Diverticulitis	1/449 (0.2%)		0/340 (0%)
Enterocolitis infectious	1/449 (0.2%)		0/340 (0%)
Erysipelas	2/449 (0.4%)		1/340 (0.3%)
Infected skin ulcer	0/449 (0%)		1/340 (0.3%)
Pneumonia	0/449 (0%)		1/340 (0.3%)
Viral infection	1/449 (0.2%)		0/340 (0%)
Injury, poisoning and procedural complications
Lower limb fracture	0/449 (0%)		1/340 (0.3%)
Meniscus lesion	1/449 (0.2%)		0/340 (0%)
Investigations
International normalised ratio increased	1/449 (0.2%)		0/340 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/449 (0.2%)		0/340 (0%)
Hyperglycaemia	1/449 (0.2%)		0/340 (0%)
Hypoglycaemia	1/449 (0.2%)		0/340 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	1/449 (0.2%)		0/340 (0%)
Lipoma	0/449 (0%)		1/340 (0.3%)
Metastases to penis	0/449 (0%)		1/340 (0.3%)
Oesophageal carcinoma	0/449 (0%)		1/340 (0.3%)
Prostate cancer	1/449 (0.2%)		1/340 (0.3%)
Renal cell carcinoma	0/449 (0%)		1/340 (0.3%)
Nervous system disorders
Subarachnoid haemorrhage	0/449 (0%)		1/340 (0.3%)
Syncope	0/449 (0%)		1/340 (0.3%)
Transient ischaemic attack	0/449 (0%)		1/340 (0.3%)
Renal and urinary disorders
Calculus urinary	0/449 (0%)		1/340 (0.3%)
Renal failure acute	2/449 (0.4%)		0/340 (0%)
Reproductive system and breast disorders
Ovarian cyst	1/449 (0.2%)		0/340 (0%)
Prostatitis	1/449 (0.2%)		0/340 (0%)
Vascular disorders
Aortic stenosis	1/449 (0.2%)		0/340 (0%)
Pelvic venous thrombosis	1/449 (0.2%)		0/340 (0%)
Subclavian artery stenosis	0/449 (0%)		1/340 (0.3%)
Other (Not Including Serious) Adverse Events
	Extended Release Niacin/Laropiprant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	251/449 (55.9%)		113/340 (33.2%)
Gastrointestinal disorders
Diarrhoea	41/449 (9.1%)		21/340 (6.2%)
Nausea	24/449 (5.3%)		12/340 (3.5%)
Infections and infestations
Nasopharyngitis	33/449 (7.3%)		25/340 (7.4%)
Upper respiratory tract infection	28/449 (6.2%)		24/340 (7.1%)
Investigations
Blood glucose increased	52/449 (11.6%)		14/340 (4.1%)
Nervous system disorders
Headache	20/449 (4.5%)		18/340 (5.3%)
Skin and subcutaneous tissue disorders
Pruritus	71/449 (15.8%)		9/340 (2.6%)
Rash	26/449 (5.8%)		5/340 (1.5%)
Vascular disorders
Flushing	79/449 (17.6%)		16/340 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.