Dyslipidemias, High Cholesterol, Hypercholesterolemia, Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease
Conditions
Keywords
obicetrapib, BROADWAY, Cholesteryl ester transfer protein (CETP) inhibitor, Heterozygous Familial Hypercholesterolemia (HeFH), Atherosclerotic Cardiovascular Disease (ASCVD)
Brief summary
This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying heterozygous familial hypercholesterolemia (HeFH) and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy
Detailed description
This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying HeFH and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 28 days. Afterwards patients will be randomized to placebo or 10 mg obicetrapib for a 365 day treatment period. After the treatment period, patients will have an end of study follow-up visit.
Interventions
DRUGPlacebo
placebo tablet made to resemble active
DRUGObicetrapib
10mg obicetrapib tablet
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
Intervention model description
Placebo-controlled, double-blind, randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females may be enrolled if all 3 of the following criteria are met: * They are not pregnant; * They are not breastfeeding; and * They do not plan on becoming pregnant during the study; * Have underlying heterozygous familial hypercholesterolemia (HeFH) and/or a history of established ASCVD * Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications, defined as follows: * A statin at a maximally tolerated stable dose for at least 8 weeks prior to Screening * Atorvastatin 40 and 80 mg; and * Rosuvastatin 20 and 40 mg; * Ezetimibe with or without maximally tolerated statin for at least 8 weeks prior to Screening * Bempedoic acid with a maximally tolerated statin for at least 8 weeks prior to Screening * A PCSK-9 targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening * Have a fasting serum LDL-C at Screening as follows: * Fasting serum LDL-C ≥ 55 to \< 100 mg/dL (≥1.4 to \<2.6 mmol/L) OR non-HDL-C ≥85 mg/dL (≥2.2 mmol/L) to \< 130 mg/dL (\<3.4 mmol/L) with at least 1 of the following risk enhancers at Screening; * Recent MI (\> 3 and \< 12 months prior to Randomization); * Type 2 diabetes mellitus; * Current daily cigarette smoking; * Age of \> 60 years; * High sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L (≥19.0 nmol/L) at Screening or within 6 months prior to Screening * Fasting triglycerides (TG) \> 150 mg/dL (\>1.7 mmol/L); * Fasting lipoprotein (a) \> 30 mg/dL (\>70 nmol/L); and/or * Fasting HDL-C \< 40 mg/dL (\<1.0 mmol/L); OR * Fasting serum LDL-C ≥ 100 mg/dL (≥2.6 mmol/L) or non-HDL-C ≥130 mg/dL (≥3.4 mmol/L) * Fasting triglyceride (TG) \< 500 mg/dL (\<5.7 mmol/L) at Screening; and * Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at Screening
Exclusion criteria
* New York Heart Association class III or IV heart failure or left ventricular ejection fraction \< 30%; * Hospitalized for heart failure within 5 years prior to Screening * Major adverse cardiac event (MACE) within 3 months prior to Screening; * Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization; * Formal diagnosis of homozygous familial hypercholesterolemia (HoFH); * Active liver disease; * HbA1c ≥10% or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening; * Thyroid-stimulating hormone \>1.5 X upper limit of normal (ULN) at Screening; * Creatine kinase \> 3 X upper limit of normal (ULN) at Screening; * History of malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization; * Known history of alcohol and/or drug abuse within 5 years prior to Randomization * Received treatment with other investigational products or devices within 30 days of Screening or 5 half-lives of the previous investigational product, whichever is longer; * Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening * Planned use of other investigational products or devices during the course of the study; * Participated in any clinical trial evaluating obicetrapib; or * Known allergy or hypersensitivity to obicetrapib, placebo, or any of the excipients in obicetrapib or placebo * Any condition that, according to the Investigator, could interfere with the conduct of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC] | 84 Days | LS mean percent change from baseline to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC] | 365 Days | LS mean percent change from baseline to Day 365 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC). |
| Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group. |
| Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180 | 180 Days | LS mean percent change from baseline to Day 180 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group. |
| Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365 | 365 Days | LS mean percent change from baseline to Day 365 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group. |
| Percent Change in Non-HDL-C From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) in obicetrapib group compared to the placebo group. |
| Percent Change in Non-HDL-C From Baseline to Day 180 | 180 Days | LS mean percent change from baseline to Day 180 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group. |
| Percent Change in Non-HDL-C From Baseline to Day 365 | 365 Days | LS mean percent change from baseline to Day 365 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group. |
| Percent Change in HDL-C From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group. |
| Percent Change in HDL-C From Baseline to Day 180 | 180 Days | LS mean percent change from baseline to Day 180 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group. |
| Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins] | 180 Days | LS mean percent change from baseline to Day 180 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[Martin/Hopkins\]. LDL-C value was calculated using the Martin/Hopkins equation unless TG \>= 400 mg/dL or LDL-C \<= 50 mg/dL; where, LDL-C value was measured directly by preparative ultracentrifugation (PUC). |
| Percent Change in Lp(a) From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group. |
| Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in Apolipoprotein A1 (ApoA1) in obicetrapib group compared to the placebo group. |
| Percent Change in Total Cholesterol From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in Total Cholesterol (TC) in obicetrapib group compared to the placebo group. |
| Percent Change in Total Cholesterol From Baseline to Day 180 | 180 Days | LS mean percent change from baseline to Day 180 in Total Cholesterol in obicetrapib group compared to the placebo group. |
| Percent Change in Total Cholesterol From Baseline to Day 365 | 365 Days | LS mean percent change from baseline to Day 365 in Total Cholesterol in obicetrapib group compared to the placebo group. |
| Percent Change in Triglycerides From Baseline to Day 84 | 84 Days | LS mean percent change from baseline to Day 84 in Triglycerides in obicetrapib group compared to the placebo group. |
| Percent Change in Triglycerides From Baseline to Day 180 | 180 Days | LS mean percent change from baseline to Day 180 in Triglycerides in obicetrapib group compared to the placebo group. |
| Percent Change in Triglycerides From Baseline to Day 365 | 365 days | LS mean percent change from baseline to Day 365 in Triglycerides in obicetrapib group compared to the placebo group. |
| Percent Change in HDL-C From Baseline to Day 365 | 365 Days | LS mean percent change from baseline to Day 365 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group. |
Countries
China, Czechia, Denmark, Georgia, Japan, Netherlands, Poland, United States
Participant flow
Recruitment details
4214 patients were screened: out of 4214, 2530 participants were randomized (2:1) (obicetrapib: placebo): 1686 participants to the obicetrapib 10 mg group and 844 participants to the placebo group
Participants by arm
| Arm | Count |
|---|---|
| Placebo one placebo tablet once daily
Placebo: placebo tablet made to resemble active | 844 |
| Obicetrapib 10mg one 10mg obicetrapib tablet once daily
Obicetrapib: 10mg obicetrapib tablet | 1,686 |
| Total | 2,530 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 11 | 17 |
| Overall Study | Lost to Follow-up | 16 | 38 |
| Overall Study | Participant Moved Away | 0 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 20 | 27 |
Baseline characteristics
| Characteristic | Placebo | Obicetrapib 10mg | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 9.61 | 65.4 years STANDARD_DEVIATION 9.9 | 65.4 years STANDARD_DEVIATION 9.8 |
| Baseline Low-Density Lipoprotein Cholesterol (LDL-C) | 98.4 mg/dL STANDARD_DEVIATION 37.94 | 98.1 mg/dL STANDARD_DEVIATION 37.05 | 98.25 mg/dL STANDARD_DEVIATION 37.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 80 Participants | 126 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 798 Participants | 1605 Participants | 2403 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 150 Participants | 312 Participants | 462 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 112 Participants | 151 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 7 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) White | 647 Participants | 1241 Participants | 1888 Participants |
| Sex: Female, Male Female | 280 Participants | 573 Participants | 853 Participants |
| Sex: Female, Male Male | 564 Participants | 1113 Participants | 1677 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 843 | 19 / 1,685 |
| other Total, other adverse events | 241 / 843 | 459 / 1,685 |
| serious Total, serious adverse events | 117 / 843 | 211 / 1,685 |
Outcome results
Primary
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC]
LS mean percent change from baseline to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC] | 2.70 percent change from baseline | Standard Error 1.571 |
| Obicetrapib 10mg | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 84 [PUC] | -29.94 percent change from baseline | Standard Error 1.104 |
p-value: <0.000195% CI: [-35.79, -29.5]ANCOVA
Secondary
Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84
LS mean percent change from baseline to Day 84 in Apolipoprotein A1 (ApoA1) in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84 | 0.26 percent change from baseline | Standard Error 0.597 |
| Obicetrapib 10mg | Percent Change in Apolipoprotein A1 (ApoA1) From Baseline to Day 84 | 43.44 percent change from baseline | Standard Error 0.686 |
Secondary
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180
LS mean percent change from baseline to Day 180 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180 | 2.23 percent change from baseline | Standard Error 1.033 |
| Obicetrapib 10mg | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 180 | -16.07 percent change from baseline | Standard Error 0.742 |
p-value: <0.000195% CI: [-20.38, -16.23]ANCOVA
Secondary
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365
LS mean percent change from baseline to Day 365 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Time frame: 365 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365 | -1.77 percent change from baseline | Standard Error 1.165 |
| Obicetrapib 10mg | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 365 | -15.57 percent change from baseline | Standard Error 0.914 |
p-value: <0.000195% CI: [-16.2, -11.41]ANCOVA
Secondary
Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84
LS mean percent change from baseline to Day 84 in apolipoprotein B (ApoB) in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84 | 1.08 percent change from baseline | Standard Error 0.911 |
| Obicetrapib 10mg | Percent Change in Apolipoprotein B (ApoB) From Baseline to Day 84 | -17.84 percent change from baseline | Standard Error 0.669 |
p-value: <0.000195% CI: [-20.76, -17.09]ANCOVA
Secondary
Percent Change in HDL-C From Baseline to Day 180
LS mean percent change from baseline to Day 180 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in HDL-C From Baseline to Day 180 | 1.18 percent change from baseline | Standard Error 1.897 |
| Obicetrapib 10mg | Percent Change in HDL-C From Baseline to Day 180 | 135.61 percent change from baseline | Standard Error 2.192 |
p-value: <0.000195% CI: [129.84, 139.03]ANCOVA
Secondary
Percent Change in HDL-C From Baseline to Day 365
LS mean percent change from baseline to Day 365 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 365 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in HDL-C From Baseline to Day 365 | 3.36 percent change from baseline | Standard Error 1.651 |
| Obicetrapib 10mg | Percent Change in HDL-C From Baseline to Day 365 | 125.40 percent change from baseline | Standard Error 2.193 |
p-value: <0.000195% CI: [117.53, 126.55]ANCOVA
Secondary
Percent Change in HDL-C From Baseline to Day 84
LS mean percent change from baseline to Day 84 in High-density Lipoprotein Cholesterol (HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in HDL-C From Baseline to Day 84 | 0.61 percent change from baseline | Standard Error 1.391 |
| Obicetrapib 10mg | Percent Change in HDL-C From Baseline to Day 84 | 136.87 percent change from baseline | Standard Error 1.857 |
p-value: <0.000195% CI: [132.46, 140.07]ANCOVA
Secondary
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins]
LS mean percent change from baseline to Day 180 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[Martin/Hopkins\]. LDL-C value was calculated using the Martin/Hopkins equation unless TG \>= 400 mg/dL or LDL-C \<= 50 mg/dL; where, LDL-C value was measured directly by preparative ultracentrifugation (PUC).
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins] | 4.68 percent change from baseline | Standard Error 1.625 |
| Obicetrapib 10mg | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 180 [Martin/Hopkins] | -29.09 percent change from baseline | Standard Error 1.176 |
p-value: <0.000195% CI: [-37.07, -30.49]ANCOVA
Secondary
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC]
LS mean percent change from baseline to Day 365 in Low-Density Lipoprotein Cholesterol (LDL-C) in the obicetrapib group compared to the placebo group \[PUC\]. LDL-C level was measured by preparative ultracentrifugation (PUC).
Time frame: 365 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC] | -1.27 percent change from baseline | Standard Error 1.798 |
| Obicetrapib 10mg | Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 365 [PUC] | -25.25 percent change from baseline | Standard Error 1.48 |
p-value: <0.000195% CI: [-27.87, -20.09]ANCOVA
Secondary
Percent Change in Lp(a) From Baseline to Day 84
LS mean percent change from baseline to Day 84 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Lp(a) From Baseline to Day 84 | 13.65 percent change from baseline | Standard Error 8.24 |
| Obicetrapib 10mg | Percent Change in Lp(a) From Baseline to Day 84 | -0.48 percent change from baseline | Standard Error 19.855 |
p-value: 0.484195% CI: [-53.68, 25.44]ANCOVA
Secondary
Percent Change in Non-HDL-C From Baseline to Day 180
LS mean percent change from baseline to Day 180 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Non-HDL-C From Baseline to Day 180 | 3.68 percent change from baseline | Standard Error 1.302 |
| Obicetrapib 10mg | Percent Change in Non-HDL-C From Baseline to Day 180 | -24.63 percent change from baseline | Standard Error 0.972 |
p-value: <0.000195% CI: [-30.94, -25.69]ANCOVA
Secondary
Percent Change in Non-HDL-C From Baseline to Day 365
LS mean percent change from baseline to Day 365 in Non-high-density Lipoprotein Cholesterol (non-HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 365 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Non-HDL-C From Baseline to Day 365 | 0.63 percent change from baseline | Standard Error 1.48 |
| Obicetrapib 10mg | Percent Change in Non-HDL-C From Baseline to Day 365 | -22.38 percent change from baseline | Standard Error 1.186 |
p-value: <0.000195% CI: [-26.09, -19.95]ANCOVA
Secondary
Percent Change in Non-HDL-C From Baseline to Day 84
LS mean percent change from baseline to Day 84 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Non-HDL-C From Baseline to Day 84 | 2.81 percent change from baseline | Standard Error 1.212 |
| Obicetrapib 10mg | Percent Change in Non-HDL-C From Baseline to Day 84 | -26.64 percent change from baseline | Standard Error 0.892 |
p-value: <0.000195% CI: [-31.89, -26.99]ANCOVA
Secondary
Percent Change in Total Cholesterol From Baseline to Day 180
LS mean percent change from baseline to Day 180 in Total Cholesterol in obicetrapib group compared to the placebo group.
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Total Cholesterol From Baseline to Day 180 | 0.85 percent change from baseline | Standard Error 0.893 |
| Obicetrapib 10mg | Percent Change in Total Cholesterol From Baseline to Day 180 | 18.68 percent change from baseline | Standard Error 0.769 |
Secondary
Percent Change in Total Cholesterol From Baseline to Day 365
LS mean percent change from baseline to Day 365 in Total Cholesterol in obicetrapib group compared to the placebo group.
Time frame: 365 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Total Cholesterol From Baseline to Day 365 | -0.58 percent change from baseline | Standard Error 1.03 |
| Obicetrapib 10mg | Percent Change in Total Cholesterol From Baseline to Day 365 | 17.96 percent change from baseline | Standard Error 0.886 |
Secondary
Percent Change in Total Cholesterol From Baseline to Day 84
LS mean percent change from baseline to Day 84 in Total Cholesterol (TC) in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Total Cholesterol From Baseline to Day 84 | -0.02 percent change from baseline | Standard Error 0.757 |
| Obicetrapib 10mg | Percent Change in Total Cholesterol From Baseline to Day 84 | 17.66 percent change from baseline | Standard Error 0.702 |
Secondary
Percent Change in Triglycerides From Baseline to Day 180
LS mean percent change from baseline to Day 180 in Triglycerides in obicetrapib group compared to the placebo group.
Time frame: 180 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Day 180 | 8.22 percent change from baseline | Standard Error 2.061 |
| Obicetrapib 10mg | Percent Change in Triglycerides From Baseline to Day 180 | 0.25 percent change from baseline | Standard Error 1.584 |
Secondary
Percent Change in Triglycerides From Baseline to Day 365
LS mean percent change from baseline to Day 365 in Triglycerides in obicetrapib group compared to the placebo group.
Time frame: 365 days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Day 365 | 6.33 percent change from baseline | Standard Error 2.135 |
| Obicetrapib 10mg | Percent Change in Triglycerides From Baseline to Day 365 | 0.60 percent change from baseline | Standard Error 1.781 |
Secondary
Percent Change in Triglycerides From Baseline to Day 84
LS mean percent change from baseline to Day 84 in Triglycerides in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Day 84 | 7.66 percent change from baseline | Standard Error 1.814 |
| Obicetrapib 10mg | Percent Change in Triglycerides From Baseline to Day 84 | -0.17 percent change from baseline | Standard Error 1.445 |
Post Hoc
Percent Change in Lp(a) From Baseline to Day 84 (Hodges-Lehman)
Median percent change from baseline to Day 84 in Lipoprotein (a) \[Lp(a)\] in obicetrapib group compared to the placebo group.
Time frame: 84 Days
Population: Baseline Population is defined as all participants who were randomized in the study. Baseline values were defined as last measurement prior to the first dose of study drug. Missing values were imputed using a multiple imputation model assuming the data are missing not at random. Missing measurements of non-retrieved dropouts were modeled by known measurements from retrieved dropouts in the same treatment group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change in Lp(a) From Baseline to Day 84 (Hodges-Lehman) | -0.9 percent change from baseline |
| Obicetrapib 10mg | Percent Change in Lp(a) From Baseline to Day 84 (Hodges-Lehman) | -32.3 percent change from baseline |