Hypercholesterolemia
Conditions
Brief summary
This study will examine the effect of ezetimibe on glucose metabolism in participants with Type 2 diabetes and hypercholesterolemia.The primary hypothesis is that change in glycated hemoglobin (HbA1c) from baseline in the ezetimibe treatment group will be non-inferior to the placebo control group.
Interventions
DRUGEzetimibe
10 mg oral dose once daily for 24 weeks
DRUGPlacebo
Placebo to match ezetimibe orally once daily for 24 weeks.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have hypercholesterolemia (high cholesterol) and have been diagnosed with type 2 diabetes that is being treated with oral anti-diabetic drugs or insulin or both. * No change in the medication (drugs, dose and administration) for the treatment of diabetes within previous 12 weeks with exception of small changes in insulin dosing * No change in diet and exercise therapy within previous 4 weeks
Exclusion criteria
* Coexisting disease (hemoglobinopathy, hemolytic anemia, etc.) that may affect HbA1c measurement * Homozygous or heterozygous familial hypercholesterolemia * Previously received ezetimibe * Hypercholesterolemia associated with: hypothyroidism, obstructive gall bladder or biliary disease, chronic renal failure or pancreatitis * Hyperlipidemia caused by medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycated Hemoglobin (HbA1c) From Baseline | Baseline and Week 24 | HbA1c is blood marker used to report average blood glucose levels over a prolonged period of time and is reported as a percentage (%). HbA1C was measured at baseline and after 24 weeks of study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) From Baseline | Baseline and Week 24 | Plasma glucose levels were assessed after an overnight fast at baseline and after 24 weeks of study drug administration. |
| Percentage of Participants With Adverse Event (AE) Exacerbation of Diabetes | up to 24 weeks | The Investigator took into account a participant's index of blood glucose control, diabetes medications, and compliance to diet and exercise therapy to assess overall control of the participant's diabetes and to determine if the participant's diabetes worsened. Participants who experienced the AE Exacerbation of Diabetes (verbatim term) were recorded. |
| Percentage of Participants With Changes in Diabetes Medications Due to Worsening of Diabetes | Up to 24 weeks | The percentage of participants who had changes to their medications used to treat their diabetes, other than small changes in insulin dosing (± 5 Units), were reported and summarized. |
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline | Baseline and Week 24 | LDL-C levels measured at baseline and after 24 weeks of treatment |
| Change in Glycoalbumin From Baseline | Baseline and Week 24 | Glycoalbumin is a blood marker used to assess blood glucose control over time and is reported as a percentage (%). Serum glycoalbumin levels were assessed at baseline and after 24 weeks of study drug administration. |
| Percent Change in Triglycerides From Baseline | Baseline and Week 24 | Triglycerides levels measured at baseline and after 24 weeks of treatment. |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline | Baseline and Week 24 | HDL-C levels measured at baseline and after 24 weeks of treatment. |
| Percent Change in Non-HDL-cholesterol From Baseline | Baseline and Week 24 | Non-HDL-C levels measured at baseline and after 24 weeks of treatment. |
| Percent Change in Total Cholesterol (TC) From Baseline | Baseline and Week 24 | TC levels measured at Baseline and after 24 weeks of treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe 10 mg oral dose once daily for 24 weeks | 75 |
| Placebo Placebo to match ezetimibe orally once daily for 24 weeks | 77 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Ezetimibe | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 10.8 | 60.0 years STANDARD_DEVIATION 9.7 | 59.6 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 29 Participants | 29 Participants | 58 Participants |
| Sex: Female, Male Male | 46 Participants | 48 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 75 | 25 / 77 |
| serious Total, serious adverse events | 2 / 75 | 5 / 77 |
Outcome results
Primary
Change in Glycated Hemoglobin (HbA1c) From Baseline
HbA1c is blood marker used to report average blood glucose levels over a prolonged period of time and is reported as a percentage (%). HbA1C was measured at baseline and after 24 weeks of study drug administration.
Time frame: Baseline and Week 24
Population: Per Protocol Set defined as all randomized participants meeting inclusion criteria who were not excluded from the Full Analysis Set and were at least 75% compliant with study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Change in Glycated Hemoglobin (HbA1c) From Baseline | 0.22 Percent |
| Placebo | Change in Glycated Hemoglobin (HbA1c) From Baseline | 0.14 Percent |
95% CI: [-0.07, 0.23]Longitudinal analysis of covariance
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline
Plasma glucose levels were assessed after an overnight fast at baseline and after 24 weeks of study drug administration.
Time frame: Baseline and Week 24
Population: Per Protocol Set defined as all randomized participants meeting inclusion criteria who were not excluded from the Full Analysis Set and were at least 75% compliant with study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Change in Fasting Plasma Glucose (FPG) From Baseline | 6.6 mg/dL |
| Placebo | Change in Fasting Plasma Glucose (FPG) From Baseline | 11.4 mg/dL |
95% CI: [-12.1, 2.5]Longitudinal Analysis of Covariance
Secondary
Change in Glycoalbumin From Baseline
Glycoalbumin is a blood marker used to assess blood glucose control over time and is reported as a percentage (%). Serum glycoalbumin levels were assessed at baseline and after 24 weeks of study drug administration.
Time frame: Baseline and Week 24
Population: Per Protocol Set defined as all randomized participants meeting inclusion criteria who were not excluded from the Full Analysis Set and were at least 75% compliant with study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Change in Glycoalbumin From Baseline | -0.02 Percent |
| Placebo | Change in Glycoalbumin From Baseline | -0.02 Percent |
95% CI: [-0.47, 0.47]Longitudinal analysis of covariance
Secondary
Percentage of Participants With Adverse Event (AE) Exacerbation of Diabetes
The Investigator took into account a participant's index of blood glucose control, diabetes medications, and compliance to diet and exercise therapy to assess overall control of the participant's diabetes and to determine if the participant's diabetes worsened. Participants who experienced the AE Exacerbation of Diabetes (verbatim term) were recorded.
Time frame: up to 24 weeks
Population: All Subjects Treated (AST) Population defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe | Percentage of Participants With Adverse Event (AE) Exacerbation of Diabetes | 9.3 Percentage of Participants |
| Placebo | Percentage of Participants With Adverse Event (AE) Exacerbation of Diabetes | 7.8 Percentage of Participants |
Comparison: Comparison of percentage difference between ezetimibe and placebop-value: 0.779Fisher Exact
Secondary
Percentage of Participants With Changes in Diabetes Medications Due to Worsening of Diabetes
The percentage of participants who had changes to their medications used to treat their diabetes, other than small changes in insulin dosing (± 5 Units), were reported and summarized.
Time frame: Up to 24 weeks
Population: AST Population defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe | Percentage of Participants With Changes in Diabetes Medications Due to Worsening of Diabetes | 9.3 Percentage of Participants |
| Placebo | Percentage of Participants With Changes in Diabetes Medications Due to Worsening of Diabetes | 5.2 Percentage of Participants |
Comparison: Comparison of percentage difference between ezetimibe and placebop-value: 0.365Fisher Exact
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline
HDL-C levels measured at baseline and after 24 weeks of treatment.
Time frame: Baseline and Week 24
Population: Full Analysis Set (FAS) defined as all enrolled participants who received at least 1 dose of study drug and baseline and follow-up data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline | 3.86 Percent Change |
| Placebo | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline | 1.41 Percent Change |
p-value: 0.24695% CI: [-1.71, 6.61]Longitudinal Analysis of Covariance
Secondary
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline
LDL-C levels measured at baseline and after 24 weeks of treatment
Time frame: Baseline and Week 24
Population: Full Analysis Set (FAS) defined as all enrolled participants who received at least 1 dose of study drug and baseline and follow-up data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline | -22.79 Percent Change |
| Placebo | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline | -1.75 Percent Change |
p-value: <0.00195% CI: [-25.06, -17.03]Longitudinal analysis of covariance
Secondary
Percent Change in Non-HDL-cholesterol From Baseline
Non-HDL-C levels measured at baseline and after 24 weeks of treatment.
Time frame: Baseline and Week 24
Population: Full Analysis Set (FAS) defined as all enrolled participants who received at least 1 dose of study drug and baseline and follow-up data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Percent Change in Non-HDL-cholesterol From Baseline | -21.32 Percent Change |
| Placebo | Percent Change in Non-HDL-cholesterol From Baseline | -2.25 Percent Change |
p-value: <0.00195% CI: [-22.71, -15.43]Longitudinal Analysis of Covariance
Secondary
Percent Change in Total Cholesterol (TC) From Baseline
TC levels measured at Baseline and after 24 weeks of treatment.
Time frame: Baseline and Week 24
Population: FAS defined as all enrolled participants who received at least 1 dose of study drug and baseline and follow-up data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Percent Change in Total Cholesterol (TC) From Baseline | -15.01 Percent Change |
| Placebo | Percent Change in Total Cholesterol (TC) From Baseline | -1.47 Percent Change |
p-value: <0.00195% CI: [-16.66, -10.42]Longitudinal analysis of covariance
Secondary
Percent Change in Triglycerides From Baseline
Triglycerides levels measured at baseline and after 24 weeks of treatment.
Time frame: Baseline and Week 24
Population: Full Analysis Set (FAS) defined as all enrolled participants who received at least 1 dose of study drug and baseline and follow-up data available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Ezetimibe | Percent Change in Triglycerides From Baseline | -7.52 Percent Change |
| Placebo | Percent Change in Triglycerides From Baseline | 3.83 Percent Change |
p-value: 0.02595% CI: [-21.27, -1.44]Longitudinal Analysis of Covariance