Trial Outcomes & Findings for Extended Niacin/Laropiprant in Patients With Type 2 Diabetes (0524A-069) (NCT NCT00485758)

NCT ID: NCT00485758

Last Updated: 2015-10-12

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 796 participants
• Primary outcome timeframe: Baseline and 12 Weeks
• Results posted on: 2015-10-12

Participant Flow

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

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.

Participant milestones

Measure	Extended Release Niacin/Laropiprant 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.	Placebo Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Overall Study STARTED	454	342
Overall Study COMPLETED	298	277
Overall Study NOT COMPLETED	156	65

Reasons for withdrawal

Measure	Extended Release Niacin/Laropiprant 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.	Placebo Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Overall Study Adverse Event	102	31
Overall Study Death	0	1
Overall Study Lost to Follow-up	5	1
Overall Study Physician Decision	3	3
Overall Study Protocol Violation	11	2
Overall Study Withdrawal by Subject	32	27
Overall Study Study Terminated by Sponsor	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Extended Release Niacin/Laropiprant n=454 Participants 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.	Placebo n=342 Participants Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.	Total n=796 Participants Total of all reporting groups
Age, Continuous	62.0 years STANDARD_DEVIATION 9.3 • n=5 Participants	62.0 years STANDARD_DEVIATION 9.4 • n=7 Participants	62.0 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants	126 Participants n=7 Participants	314 Participants n=5 Participants
Sex: Female, Male Male	266 Participants n=5 Participants	216 Participants n=7 Participants	482 Participants n=5 Participants
Fasting Plasma Glucose	132.0 milligrams/deciliter STANDARD_DEVIATION 33.9 • n=5 Participants	133.6 milligrams/deciliter STANDARD_DEVIATION 32.4 • n=7 Participants	132.7 milligrams/deciliter STANDARD_DEVIATION 33.3 • n=5 Participants
High-density lipoprotein cholesterol	49.93 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.49 • n=5 Participants	50.26 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.23 • n=7 Participants	50.07 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.37 • n=5 Participants
Low-density lipoprotein cholesterol	87.19 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 20.54 • n=5 Participants	85.22 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 18.00 • n=7 Participants	86.34 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 19.50 • n=5 Participants
Triglycerides	126.00 milligrams/deciliter (mg/dl) n=5 Participants	129.00 milligrams/deciliter (mg/dl) n=7 Participants	127.00 milligrams/deciliter (mg/dl) n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 Weeks

Population: Full Analysis Set

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

Outcome measures

Measure	Extended Release Niacin/Laropiprant n=432 Participants 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.	Placebo n=336 Participants Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
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	-15.8 Percent change at Wk 12 compared to Bl Interval -18.4 to -13.2	2.1 Percent change at Wk 12 compared to Bl Interval 0.3 to 4.6

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

Population: Full Analysis Set

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

Outcome measures

Measure	Extended Release Niacin/Laropiprant n=432 Participants 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.	Placebo n=336 Participants Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
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	25.4 Percent change at Wk 12 compared to Bl Interval 23.4 to 27.5	2.2 Percent change at Wk 12 compared to Bl Interval 0.6 to 3.8

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

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

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

Outcome measures

Measure	Extended Release Niacin/Laropiprant n=400 Participants 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.	Placebo n=328 Participants Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Triglycerides in Patients With Type 2 Diabetes When Compared to Placebo	-22.2 Percent change at Wk 12 compared to Bl Interval -25.5 to -18.8	2.3 Percent change at Wk 12 compared to Bl Interval -1.6 to 6.2

Adverse Events

Extended Release Niacin/Laropiprant

Serious events: 26 serious events

Other events: 251 other events

Deaths: 0 deaths

Placebo

Serious events: 24 serious events

Other events: 113 other events

Deaths: 0 deaths

Serious adverse events

Measure	Extended Release Niacin/Laropiprant n=449 participants at risk 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.	Placebo n=340 participants at risk Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Blood and lymphatic system disorders Anaemia	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Cardiac disorders Angina pectoris	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Cardiac disorders Angina unstable	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.59% 2/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Cardiac disorders Aortic valve stenosis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Cardiac disorders Coronary artery disease	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.59% 2/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Cardiac disorders Myocardial infarction	0.45% 2/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Eye disorders Cataract	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Abdominal hernia	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Diverticulum	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Gastric ulcer	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Haematochezia	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Mechanical ileus	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Pancreatitis	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
General disorders Chest pain	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
General disorders Non-cardiac chest pain	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.59% 2/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Hepatobiliary disorders Cholecystitis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Diverticulitis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Enterocolitis infectious	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Erysipelas	0.45% 2/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Infected skin ulcer	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Pneumonia	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Viral infection	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Injury, poisoning and procedural complications Meniscus lesion	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Metabolism and nutrition disorders Diabetes mellitus	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Metabolism and nutrition disorders Hyperglycaemia	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Metabolism and nutrition disorders Hypoglycaemia	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to penis	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Nervous system disorders Syncope	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Nervous system disorders Transient ischaemic attack	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Renal and urinary disorders Calculus urinary	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Renal and urinary disorders Renal failure acute	0.45% 2/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Reproductive system and breast disorders Ovarian cyst	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Reproductive system and breast disorders Prostatitis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Vascular disorders Aortic stenosis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Vascular disorders Pelvic venous thrombosis	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Vascular disorders Subclavian artery stenosis	0.00% 0/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.29% 1/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Investigations International normalised ratio increased	0.22% 1/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	0.00% 0/340 7 randomized patients took no study drug dose and were not included in the safety follow-up

Other adverse events

Measure	Extended Release Niacin/Laropiprant n=449 participants at risk 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.	Placebo n=340 participants at risk Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study.
Gastrointestinal disorders Diarrhoea	9.1% 41/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	6.2% 21/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Gastrointestinal disorders Nausea	5.3% 24/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	3.5% 12/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Nasopharyngitis	7.3% 33/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	7.4% 25/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Infections and infestations Upper respiratory tract infection	6.2% 28/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	7.1% 24/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Investigations Blood glucose increased	11.6% 52/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	4.1% 14/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Nervous system disorders Headache	4.5% 20/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	5.3% 18/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Skin and subcutaneous tissue disorders Pruritus	15.8% 71/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	2.6% 9/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Skin and subcutaneous tissue disorders Rash	5.8% 26/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	1.5% 5/340 7 randomized patients took no study drug dose and were not included in the safety follow-up
Vascular disorders Flushing	17.6% 79/449 7 randomized patients took no study drug dose and were not included in the safety follow-up	4.7% 16/340 7 randomized patients took no study drug dose and were not included in the safety follow-up

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

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