Hypercholesterolemia
Conditions
Brief summary
The purpose of this study is to test the safety and effectiveness of MK-6213 as compared to MK-6213/Atorvastatin in participants 18 to 75 years) with high cholesterol.
Interventions
DRUGMK-6213
MK-6213 160 mg for 4 weeks.
DRUGAtorvastatin calcium
atorvastatin calcium 20mg for 4 weeks.
DRUGPlacebo for MK-6312 160 mg
DRUGPlacebo for Atorvastatin 20 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 75 years of age at the time of the study with high cholesterol * Can have diabetes mellitus but is not currently on lipid lowering therapy * Have a stable weight for \>6 weeks
Exclusion criteria
* Has significant cardiovascular (heart), renal (kidney), neurologic (nervous system), respiratory (lung), hepatic (liver) or metabolic disease * history of mental instability or drug/alcohol abuse within the past 5 years * Pregnant or nursing; human immunodeficiency virus (HIV) positive; history of cancer within the past 5 years or participation in an investigational trial within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by reflex beta-quantitation method. The percentage change from baseline at Week 4 was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Had Study Drug Discontinued Due to an AE | up to 4 weeks | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized. |
| Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine non-HDL-C levels. The percentage change from baseline at Week 4 was summarized. |
| Percentage Change From Baseline in Apolipoprotein B (ApoB) | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine ApoB levels. The percentage change from baseline at Week 4 was summarized. |
| Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | Up to 14 days post last dose of study drug (up to 6 weeks) | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized |
| Percentage Change From Baseline in HDL-C | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine HDL-C levels. The percentage change from baseline at Week 4 was summarized. |
| Percentage Change From Baseline in TG | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine TG levels. The percentage change from baseline at Week 4 was summarized. |
| Percentage Change From Baseline in Total Cholesterol (TC) | Baseline (predose) and Week 4 | Blood collected at baseline (predose) and after 4 weeks of treatment to determine TC levels. The percentage change from baseline at Week 4 was summarized. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg 1 MK-6213 160-mg tablet co-administered orally with 1 Atorvastatin 20-mg tablet once daily for 4 weeks | 94 |
| Atorvastatin 20 mg 1 Atorvastatin 20-mg tablet co-administered orally with 1 tablet of placebo for MK-6312 once daily for 4 weeks | 96 |
| MK-6213 160 mg 1 MK-6213 160-mg tablet co-administered orally with 1 tablet of placebo for Atorvastatin 20-mg once daily for 4 weeks | 96 |
| Placebo 1 tablet of placebo for MK-6213 160 mg co-administered orally with 1 tablet of placebo for Atorvastatin 20-mg tablet once daily for 4 weeks | 48 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | MK-6213 160 mg + Atorvastatin 20 mg | Atorvastatin 20 mg | MK-6213 160 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 10.9 | 53.6 Years STANDARD_DEVIATION 10.2 | 56.2 Years STANDARD_DEVIATION 10 | 54.7 Years STANDARD_DEVIATION 10.7 | 54.3 Years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 45 Participants | 60 Participants | 47 Participants | 26 Participants | 178 Participants |
| Sex: Female, Male Male | 49 Participants | 36 Participants | 49 Participants | 22 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 95 | 0 / 96 | 0 / 48 |
| other Total, other adverse events | 3 / 94 | 5 / 95 | 5 / 96 | 2 / 48 |
| serious Total, serious adverse events | 0 / 94 | 0 / 95 | 0 / 96 | 0 / 48 |
Outcome results
Primary
Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Blood collected at baseline (predose) and after 4 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by reflex beta-quantitation method. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | -50.7 Percentage Change |
| Atorvastatin 20 mg | Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | -40.6 Percentage Change |
| MK-6213 160 mg | Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | -13.3 Percentage Change |
| Placebo | Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | 4.6 Percentage Change |
95% CI: [-14.6, -5.5]Longitudinal Data Analysis (LDA) model
95% CI: [-23.4, -12.5]LDA model
Secondary
Percentage Change From Baseline in Apolipoprotein B (ApoB)
Blood collected at baseline (predose) and after 4 weeks of treatment to determine ApoB levels. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in Apolipoprotein B (ApoB) | -40.4 Percentage Change |
| Atorvastatin 20 mg | Percentage Change From Baseline in Apolipoprotein B (ApoB) | -32.7 Percentage Change |
| MK-6213 160 mg | Percentage Change From Baseline in Apolipoprotein B (ApoB) | -8.8 Percentage Change |
| Placebo | Percentage Change From Baseline in Apolipoprotein B (ApoB) | 3.5 Percentage Change |
95% CI: [-11.5, -3.9]LDA model
95% CI: [-16.8, -7.6]LDA model
Secondary
Percentage Change From Baseline in HDL-C
Blood collected at baseline (predose) and after 4 weeks of treatment to determine HDL-C levels. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in HDL-C | 3.8 Percentage Change |
| Atorvastatin 20 mg | Percentage Change From Baseline in HDL-C | 6.2 Percentage Change |
| MK-6213 160 mg | Percentage Change From Baseline in HDL-C | 1.4 Percentage Change |
| Placebo | Percentage Change From Baseline in HDL-C | 2.1 Percentage Change |
95% CI: [-6.6, 1.8]LDA model
95% CI: [-5.8, 4.4]LDA model
Secondary
Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)
Blood collected at baseline (predose) and after 4 weeks of treatment to determine non-HDL-C levels. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -46.6 Percentage Change |
| Atorvastatin 20 mg | Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -38.0 Percentage Change |
| MK-6213 160 mg | Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | -11.4 Percentage Change |
| Placebo | Percentage Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) | 2.5 Percentage Change |
95% CI: [-12.7, -4.4]LDA model
95% CI: [-18.9, -8.9]LDA model
Secondary
Percentage Change From Baseline in TG
Blood collected at baseline (predose) and after 4 weeks of treatment to determine TG levels. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in TG | -24.2 Percentage of Participants |
| Atorvastatin 20 mg | Percentage Change From Baseline in TG | -25.9 Percentage of Participants |
| MK-6213 160 mg | Percentage Change From Baseline in TG | 1.6 Percentage of Participants |
| Placebo | Percentage Change From Baseline in TG | -7.1 Percentage of Participants |
95% CI: [-7.7, 5.9]LDA model
95% CI: [-4.6, 16.9]LDA model
Secondary
Percentage Change From Baseline in Total Cholesterol (TC)
Blood collected at baseline (predose) and after 4 weeks of treatment to determine TC levels. The percentage change from baseline at Week 4 was summarized.
Time frame: Baseline (predose) and Week 4
Population: All participants that received at least 1 dose of study drug, had baseline value for parameter and had data available for timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage Change From Baseline in Total Cholesterol (TC) | -35.1 Percentage Change |
| Atorvastatin 20 mg | Percentage Change From Baseline in Total Cholesterol (TC) | -27.6 Percentage Change |
| MK-6213 160 mg | Percentage Change From Baseline in Total Cholesterol (TC) | -8.5 Percentage Change |
| Placebo | Percentage Change From Baseline in Total Cholesterol (TC) | 2.5 Percentage Change |
95% CI: [-10.8, -4.1]LDA model
95% CI: [-15.1, -7]LDA model
Secondary
Percentage of Participants That Had Study Drug Discontinued Due to an AE
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized.
Time frame: up to 4 weeks
Population: All participants that received at least 1 dose for study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage of Participants That Had Study Drug Discontinued Due to an AE | 1.1 Percentage of Participants |
| Atorvastatin 20 mg | Percentage of Participants That Had Study Drug Discontinued Due to an AE | 3.1 Percentage of Participants |
| MK-6213 160 mg | Percentage of Participants That Had Study Drug Discontinued Due to an AE | 1.0 Percentage of Participants |
| Placebo | Percentage of Participants That Had Study Drug Discontinued Due to an AE | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized
Time frame: Up to 14 days post last dose of study drug (up to 6 weeks)
Population: All participants that received at least 1 dose for study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-6213 160 mg + Atorvastatin 20 mg | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 33.0 Percentage of Participants |
| Atorvastatin 20 mg | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 37.9 Percentage of Participants |
| MK-6213 160 mg | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 29.2 Percentage of Participants |
| Placebo | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 41.7 Percentage of Participants |