Diabetes Mellitus Type 2
Conditions
Brief summary
A study to assess the efficacy and tolerability of ER (Extended Release) niacin/laropiprant versus placebo in Type 2 Diabetes Mellitus patients.
Interventions
One tablet of ER niacin/laropiprant (1g); advancing to ER niacin/laropiprant (2g) at Week 4 for the remainder of the study 36 Weeks.
ER niacin/laropiprant Placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 454 |
| Placebo Matching placebo added to lipid modifying regimen and continued on this regimen for remainder of the study. | 342 |
| Total | 796 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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 | Study Terminated by Sponsor | 3 | 0 |
| Overall Study | Withdrawal by Subject | 32 | 27 |
Baseline characteristics
| Characteristic | Extended Release Niacin/Laropiprant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 9.3 | 62.0 years STANDARD_DEVIATION 9.4 | 62.0 years STANDARD_DEVIATION 9.3 |
| Fasting Plasma Glucose | 132.0 milligrams/deciliter STANDARD_DEVIATION 33.9 | 133.6 milligrams/deciliter STANDARD_DEVIATION 32.4 | 132.7 milligrams/deciliter STANDARD_DEVIATION 33.3 |
| High-density lipoprotein cholesterol | 49.93 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.49 | 50.26 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.23 | 50.07 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 13.37 |
| Low-density lipoprotein cholesterol | 87.19 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 20.54 | 85.22 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 18 | 86.34 milligrams/deciliter (mg/dl) STANDARD_DEVIATION 19.5 |
| Sex: Female, Male Female | 188 Participants | 126 Participants | 314 Participants |
| Sex: Female, Male Male | 266 Participants | 216 Participants | 482 Participants |
| Triglycerides | 126.00 milligrams/deciliter (mg/dl) | 129.00 milligrams/deciliter (mg/dl) | 127.00 milligrams/deciliter (mg/dl) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 251 / 449 | 113 / 340 |
| serious Total, serious adverse events | 26 / 449 | 24 / 340 |
Outcome results
Primary
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
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
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Extended Release Niacin/Laropiprant | 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 |
| Placebo | 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 | 2.1 Percent change at Wk 12 compared to Bl |
p-value: <0.00195% CI: [-21.4, -14.4]Wilcoxon (Mann-Whitney)
Secondary
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
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
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Extended Release Niacin/Laropiprant | 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 |
| Placebo | 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 | 2.2 Percent change at Wk 12 compared to Bl |
p-value: <0.00195% CI: [20.7, 25.7]Repeated Measures Analysis
Secondary
Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Triglycerides in Patients With Type 2 Diabetes When Compared to Placebo
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
Population: Full Analysis Set With at Least one Post-Titration Visit Measurement
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Extended Release Niacin/Laropiprant | 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 |
| Placebo | Percent Change at Week (Wk) 12 Compared to Baseline (Bl) in Triglycerides in Patients With Type 2 Diabetes When Compared to Placebo | 2.3 Percent change at Wk 12 compared to Bl |
p-value: <0.00195% CI: [-27.2, -18.9]ANCOVA