Cardiovascular Disorder, Diabetes Mellitus
Conditions
Keywords
cardiovascular disorder
Brief summary
The purpose of this study is to determine the efficacy of switching to a combination tablet ezetimibe/simvastatin (10mg/20mg) versus rosuvastatin (10 mg) versus doubling the statin dose in those patients who have cardiovascular disease and diabetes mellitus not adequately controlled on simvastatin 20 mg or atorvastatin 10 mg.
Interventions
ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.
DRUGsimvastatin 40 mg or atorvastatin 20 mg
simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.
DRUGRosuvastatin
rosuvastatin 10 mg tablets, taken once daily for six weeks.
DRUGatorvastatin 10 mg or simvastatin 20 mg
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patient has not taken common statins or ezetimibe within 6 weeks of study screening or patient is currently taking a daily dose of the following statins for 6 weeks prior to study screening: simvastatin, atorvastatin, pravastatin, fluvastatin, ezetimibe, lovastatin, or ezetimibe + fluvastatin * Patient is willing to go on a cholesterol and glucose lowering diet for the duration of the study * Patient is willing to remain abstinent or use birth control for the duration of the study * Patient has Diabetes Mellitus with cardiovascular disease
Exclusion criteria
* Patient has sensitivity to certain common statin drugs * Patient is Asian and would not be able to start taking the higher doses of rosuvastatin necessary for the study design * Patient consumes more than 2 alcoholic drinks per day * Patient is pregnant or breast-feeding * Patient has been treated with other investigational drugs within 30 days of first visit * Patient is currently on prohibited doses of the following statin drugs: rosuvastatin, simvastatin, atorvastatin, and pravastatin * Patient has congestive heart failure * Patient has uncontrolled high blood pressure * Patient has kidney disease * Patient has uncontrolled endocrine or metabolic disease which are known to possibly increase blood lipoproteins * Patient has diabetes mellitus that is not well controlled * Patient is human immunodeficiency virus (HIV) positive * Patient is currently taking medications that inhibit Cytochrome P450 3A4 (CYP3A4) * Patient is currently taking therapies that would increase the risk of muscle weakness * Patient has been taking certain over- the-counter lipid-lowering agents within 6 weeks prior to visit 1 * Patient is currently taking psyllium or other fiber-based laxatives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin). | Baseline and Week 6 |
Secondary
| Measure | Time frame |
|---|---|
| In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin | Baseline and Week 6 |
| Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin | Baseline and Week 6 |
| Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | Week 6 |
| In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | Week 6 |
| In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | Week 6 |
| Percent Change From Baseline in Total Cholesterol (TC) | Baseline and Week 6 |
| Percent Change From Baseline in Triglycerides | Baseline and Week 6 |
| Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | Baseline and Week 6 |
| In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin | Baseline and Week 6 |
| Percent Change From Baseline in LDL-C/HDL-C Ratio | Baseline and Week 6 |
| Percent Change From Baseline in TC/HDL-C Ratio | Baseline and Week 6 |
| Percent Change From Baseline in Non-HDL-C/HDL-C Ratio | Baseline and Week 6 |
| Percent Change From Baseline in Apolipoprotein B (Apo B) | Baseline and Week 6 |
| Percent Change From Baseline Apolipoprotein A-I (Apo A-I) | Baseline and Week 6 |
| Percent Change From Baseline in Apo B/Apo A-I Ratio | Baseline and Week 6 |
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) | Baseline and Week 6 |
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline and Week 6 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe/Simvastatin Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks | 322 |
| Doubling Statin Dose simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks. | 162 |
| Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks. | 324 |
| Total | 808 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 2 | 6 |
Baseline characteristics
| Characteristic | Ezetimibe/Simvastatin | Doubling Statin Dose | Rosuvastatin | Total |
|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.8 | 64.7 years STANDARD_DEVIATION 8.3 | 63.6 years STANDARD_DEVIATION 8.4 | 64.0 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 162 Participants | 82 Participants | 142 Participants | 386 Participants |
| Sex: Female, Male Male | 160 Participants | 80 Participants | 182 Participants | 422 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 321 | 0 / 162 | 0 / 323 |
| serious Total, serious adverse events | 2 / 321 | 1 / 162 | 2 / 323 |
Outcome results
Primary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin).
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin). | -23.13 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin). | -8.37 Percent change |
p-value: <0.00195% CI: [-19.61, -9.91]Longitudinal data analysis (LDA)
Secondary
In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time frame: Week 6
Population: Analysis performed on subpopulation of participants who were previously treated with atorvastatin 10 mg and were switched to either Ezetimibe/simvastatin or had atorvastatin dose doubled to 20 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe/Simvastatin | In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 87 participants |
| Doubling Statin Dose | In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 24 participants |
p-value: <0.00195% CI: [1.9, 6.6]Regression, Logistic
Secondary
In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin
Time frame: Baseline and Week 6
Population: Analysis performed on subpopulation of participants who were previously treated with atorvastatin 10 mg and were switched to either Ezetimibe/simvastatin or had atorvastatin dose doubled to 20 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin | -24.58 Percent change |
| Doubling Statin Dose | In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin | -8.85 Percent change |
p-value: <0.00195% CI: [-22.65, -8.81]Longitudinal Data Analysis (LDA)
Secondary
In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time frame: Week 6
Population: Analysis performed on subpopulation of participants who were previously treated with simvastatin 20 mg and were switched to either Ezetimibe/simvastatin or had simvastatin dose doubled to 40 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe/Simvastatin | In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 84 participants |
| Doubling Statin Dose | In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 19 participants |
p-value: <0.00195% CI: [2.3, 8.5]Regression, Logistic
Secondary
In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin
Time frame: Baseline and Week 6
Population: Analysis performed on subpopulation of participants who were previously treated with simvastatin 20 mg and were switched to either Ezetimibe/simvastatin or had simvastatin dose doubled to 40 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin | -21.59 Percent change |
| Doubling Statin Dose | In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin | -7.98 Percent change |
p-value: <0.00195% CI: [-20.44, -6.79]Longitudinal data analysis (LDA)
Secondary
Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time frame: Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe/Simvastatin | Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 171 participants |
| Doubling Statin Dose | Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 43 participants |
| Rosuvastatin | Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) | 134 participants |
p-value: <0.00195% CI: [2.5, 6.2]Regression, Logistic
p-value: <0.00195% CI: [1.3, 2.6]Regression, Logistic
Secondary
Percent Change From Baseline Apolipoprotein A-I (Apo A-I)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline Apolipoprotein A-I (Apo A-I) | 0.64 Percent change |
| Doubling Statin Dose | Percent Change From Baseline Apolipoprotein A-I (Apo A-I) | -0.93 Percent change |
| Rosuvastatin | Percent Change From Baseline Apolipoprotein A-I (Apo A-I) | 0.86 Percent change |
p-value: 0.21895% CI: [-0.93, 4.06]Longitudinal data analysis (LDA)
p-value: 0.83295% CI: [-2.27, 1.83]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Apo B/Apo A-I Ratio
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Apo B/Apo A-I Ratio | -13.67 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in Apo B/Apo A-I Ratio | -4.75 Percent change |
| Rosuvastatin | Percent Change From Baseline in Apo B/Apo A-I Ratio | -11.14 Percent change |
p-value: <0.00195% CI: [-13.36, -4.47]Longitudinal data analysis (LDA)
p-value: 0.17595% CI: [-6.17, 1.13]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo B)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Apolipoprotein B (Apo B) | -14.98 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in Apolipoprotein B (Apo B) | -6.97 Percent change |
| Rosuvastatin | Percent Change From Baseline in Apolipoprotein B (Apo B) | -12.03 Percent change |
p-value: <0.00195% CI: [-11.46, -4.56]Longitudinal data analysis (LDA)
p-value: 0.04195% CI: [-5.78, -0.12]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | 1.47 percent change |
| Doubling Statin Dose | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | 1.00 percent change |
| Rosuvastatin | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | 1.99 percent change |
p-value: 0.75695% CI: [-2.5, 3.45]Longitudinal data analysis (LDA)
p-value: 0.67595% CI: [-2.96, 1.92]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) | -4.42 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) | -1.64 Percent change |
| Rosuvastatin | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) | -9.11 Percent change |
p-value: 0.74995% CI: [-19.88, 14.32]Longitudinal data analysis (LDA)
p-value: 0.49495% CI: [-8.73, 18.1]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed primarily based upon the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin | -23.13 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin | -19.32 Percent change |
p-value: 0.0695% CI: [-7.78, 0.17]Longitudinal Data Analysis
Secondary
Percent Change From Baseline in LDL-C/HDL-C Ratio
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in LDL-C/HDL-C Ratio | -21.55 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in LDL-C/HDL-C Ratio | -7.39 Percent change |
| Rosuvastatin | Percent Change From Baseline in LDL-C/HDL-C Ratio | -18.99 Percent change |
p-value: <0.00195% CI: [-20.23, -8.1]Longitudinal data analysis (LDA)
p-value: 0.31395% CI: [-7.53, 2.41]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio | -16.77 percent change |
| Doubling Statin Dose | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio | -5.32 percent change |
| Rosuvastatin | Percent Change From Baseline in Non-HDL-C/HDL-C Ratio | -14.64 percent change |
p-value: <0.00195% CI: [-17.16, -5.75]Longitudinal data analysis (LDA)
p-value: 0.37195% CI: [-6.81, 2.54]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -18.39 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -6.77 Percent change |
| Rosuvastatin | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -15.14 Percent change |
p-value: <0.00195% CI: [-15.93, -7.31]Longitudinal data analysis (LDA)
p-value: 0.07895% CI: [-6.71, 0.35]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in TC/HDL-C Ratio
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in TC/HDL-C Ratio | -12.52 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in TC/HDL-C Ratio | -4.36 Percent change |
| Rosuvastatin | Percent Change From Baseline in TC/HDL-C Ratio | -10.70 Percent change |
p-value: <0.00195% CI: [-12.1, -4.23]Longitudinal data analysis (LDA)
p-value: 0.26695% CI: [-5.05, 1.4]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Total Cholesterol (TC)
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Total Cholesterol (TC) | -13.21 Percent Change | 95% Confidence Interval 17.69 |
| Doubling Statin Dose | Percent Change From Baseline in Total Cholesterol (TC) | -4.88 Percent Change | 95% Confidence Interval 15.14 |
| Rosuvastatin | Percent Change From Baseline in Total Cholesterol (TC) | -10.58 Percent Change | 95% Confidence Interval 15.18 |
p-value: <0.00195% CI: [-11.38, -5.28]Longitudinal data analysis (LDA)
p-value: 0.03995% CI: [-5.13, -0.13]Longitudinal data analysis (LDA)
Secondary
Percent Change From Baseline in Triglycerides
Time frame: Baseline and Week 6
Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe/Simvastatin | Percent Change From Baseline in Triglycerides | -5.51 Percent change |
| Doubling Statin Dose | Percent Change From Baseline in Triglycerides | -2.63 Percent change |
| Rosuvastatin | Percent Change From Baseline in Triglycerides | -3.35 Percent change |
p-value: 0.31695% CI: [-8.53, 2.77]Longitudinal data analysis (LDA)
p-value: 0.35695% CI: [-6.75, 2.43]Longitudinal data analysis (LDA)