Dyslipidemias, High Cholesterol, Hypercholesterolemia
Conditions
Keywords
obicetrapib, statin, LDL-C, cholesterol, atherosclerosis
Brief summary
This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy.
Detailed description
This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy. The screening period for this study will take up to 2-weeks. Afterwards patients will be randomized to placebo, 10 mg obicetrapib monotherapy, or 10 mg obicetrapib + 10 mg ezetimibe combination therapy for a 12-week treatment period. After the treatment period, patients will continue for a 4-week safety follow-up.
Interventions
DRUGObicetrapib
tablets
DRUGEzetimibe 10mg
capsules; 10 mg ezetimibe tablets filled into capsule shells, 1 tablet per capsule.
OTHERObicetrapib placebo
tablets; no active ingredient
OTHEREzetimibe placebo
capsules; no active ingredient
Sponsors
NewAmsterdam Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
placebo tablet made to resemble active; placebo capsule made to resemble active
Intervention model description
Placebo-controlled, double-blind, randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* LDL-C \> 70 mg/dL and Triglycerides \< 400 mg/dL, * Treated with a high-intensity statin therapy
Exclusion criteria
* BMI \>= 40 kg/m2 * Significant cardiovascular disease * HbA1c \>= 10% * Uncontrolled hypertension * Active muscle disease * estimated glomerular filtration rate \< 60 mL/min * Hepatic dysfunction * History of participation in any clinical trial evaluating obicetrapib * Anemia * History of malignancy * Alcohol abuse * Treatment with investigational product * Treatment with PCSK9 * Clinically significant condition * Known CETP inhibitor allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | 12-weeks | Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | 12-Weeks | Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | 12-Weeks | LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | 12-Weeks | Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
| Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | 12-Weeks | Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
| LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | 12-Weeks | LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | 12-weeks | Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group |
| Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | 12-Weeks | Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group |
| LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | 12-Weeks | LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group |
| Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | 12-weeks | Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | 12-Weeks | Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group |
| LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | 12-Weeks | LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group |
| Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | 12-weeks | Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group |
| Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | 12-Weeks | Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | 12-Weeks | LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC). |
| Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | 12-Weeks | Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
| Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | 12-Weeks | Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
| LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | 12-Weeks | LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC). |
Countries
United States
Participant flow
Recruitment details
231 participants were screened; out of 231, 119 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo once-daily placebo tablet and placebo capsule
Obicetrapib placebo: tablets; no active ingredient
Ezetimibe placebo: capsules; no active ingredient | 40 |
| Monotherapy once-daily obicetrapib 10 mg tablet and placebo capsule
Obicetrapib: tablets
Ezetimibe placebo: capsules; no active ingredient | 26 |
| Combination Therapy once-daily obicetrapib 10 mg tablet and ezetimibe 10 mg capsule
Obicetrapib: tablets
Ezetimibe 10mg: capsules; 10 mg ezetimibe tablets filled into capsule shells, 1 tablet per capsule. | 31 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 |
| Overall Study | Non-compliance with study drug | 0 | 1 | 0 |
| Overall Study | Subject unable to adhere to all protocol requirements | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Monotherapy | Combination Therapy |
|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 8.48 | 60.6 years STANDARD_DEVIATION 8.46 | 64.8 years STANDARD_DEVIATION 7.24 | 63.5 years STANDARD_DEVIATION 9.08 |
| Baseline Low-Density Lipoprotein Cholesterol (LDL-C) Values | 98.57 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 28.78 | 99.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 27.06 | 100.6 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 33.65 | 96.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 25.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 4 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 35 Participants | 24 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 82 Participants | 30 Participants | 23 Participants | 29 Participants |
| Sex: Female, Male Female | 35 Participants | 14 Participants | 9 Participants | 12 Participants |
| Sex: Female, Male Male | 62 Participants | 26 Participants | 17 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 16 / 40 | 8 / 39 | 11 / 40 |
| serious Total, serious adverse events | 1 / 40 | 1 / 39 | 0 / 40 |
Outcome results
Primary
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]
LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -0.85 percent change from baseline | Standard Error 3.472 |
| Combination Therapy | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -59.23 percent change from baseline | Standard Error 3.786 |
p-value: <0.000195% CI: [-68.59, -48.18]Mixed Models Analysis
Primary
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]
LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -1.54 percent change from baseline | Standard Error 3.533 |
| Combination Therapy | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -59.69 percent change from baseline | Standard Error 3.811 |
p-value: <0.000195% CI: [-68.47, -47.83]ANCOVA
Primary
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]
Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -0.83 percent change from baseline | Standard Deviation 24.514 |
| Combination Therapy | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -59.07 percent change from baseline | Standard Deviation 14.814 |
p-value: <0.000195% CI: [-68.59, -48.18]Mixed Models Analysis
Primary
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]
Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -1.49 percent change from baseline | Standard Deviation 23.762 |
| Combination Therapy | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -59.51 percent change from baseline | Standard Deviation 15.192 |
p-value: <0.000195% CI: [-68.47, -47.83]ANCOVA
Primary
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]
Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -6.35 percent change from baseline |
| Combination Therapy | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald] | -63.40 percent change from baseline |
p-value: <0.000195% CI: [-68.59, -48.18]Mixed Models Analysis
Primary
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]
Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -3.95 percent change from baseline |
| Combination Therapy | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC] | -62.80 percent change from baseline |
p-value: <0.000195% CI: [-68.47, -47.83]ANCOVA
Secondary
LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo
LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | 0.72 percent change from baseline | Standard Error 2.572 |
| Combination Therapy | LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | -21.56 percent change from baseline | Standard Error 3.052 |
p-value: <0.000195% CI: [-30.21, -14.36]Mixed Models Analysis
Secondary
LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo
LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | 0.72 percent change from baseline | Standard Error 2.572 |
| Combination Therapy | LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | -34.95 percent change from baseline | Standard Error 2.796 |
p-value: <0.000195% CI: [-43.23, -28.13]Mixed Models Analysis
Secondary
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]
LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -0.85 percent change from baseline | Standard Error 3.472 |
| Combination Therapy | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -39.20 percent change from baseline | Standard Error 4.133 |
p-value: <0.000195% CI: [-49.07, -27.63]Mixed Models Analysis
Secondary
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]
LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -1.54 percent change from baseline | Standard Error 3.533 |
| Combination Therapy | LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -38.75 percent change from baseline | Standard Error 4.166 |
p-value: <0.000195% CI: [-48.07, -26.35]ANCOVA
Secondary
Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo
Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
Time frame: 12-weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | 0.51 percent change from baseline | Standard Deviation 19.784 |
| Combination Therapy | Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | -21.73 percent change from baseline | Standard Deviation 16.057 |
p-value: <0.000195% CI: [-30.21, -14.36]Mixed Models Analysis
Secondary
Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo
Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group
Time frame: 12-weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | 0.51 percent change from baseline | Standard Deviation 19.784 |
| Combination Therapy | Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | -34.66 percent change from baseline | Standard Deviation 11.796 |
p-value: <0.000195% CI: [-43.23, -28.13]Mixed Models Analysis
Secondary
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]
Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -0.83 percent change from baseline | Standard Deviation 24.514 |
| Combination Therapy | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -39.35 percent change from baseline | Standard Deviation 22.602 |
p-value: <0.000195% CI: [-49.07, -27.63]Mixed Models Analysis
Secondary
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]
Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -1.49 percent change from baseline | Standard Deviation 23.762 |
| Combination Therapy | Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -39.04 percent change from baseline | Standard Deviation 23.456 |
p-value: <0.000195% CI: [-48.07, -26.35]ANCOVA
Secondary
Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo
Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | -2.05 percent change from baseline |
| Combination Therapy | Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo | -24.20 percent change from baseline |
p-value: <0.000195% CI: [-30.21, -14.36]Mixed Models Analysis
Secondary
Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo
Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | -2.05 percent change from baseline |
| Combination Therapy | Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo | -34.40 percent change from baseline |
p-value: <0.000195% CI: [-43.23, -28.13]Mixed Models Analysis
Secondary
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]
Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -6.35 percent change from baseline |
| Combination Therapy | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald] | -43.50 percent change from baseline |
p-value: <0.000195% CI: [-49.07, -27.63]Mixed Models Analysis
Secondary
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]
Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 12-Weeks
Population: On-treatment defined as all randomized participants who received at least 1 dose of any study drug and had a baseline value for low-density lipoprotein cholesterol (LDL-C), excluding those with PK evidence suggesting participant misconduct, i.e., plasma obicetrapib \< 100 ng/mL.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -3.95 percent change from baseline |
| Combination Therapy | Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC] | -43.55 percent change from baseline |
p-value: <0.000195% CI: [-48.07, -26.35]ANCOVA