Familial Hypercholesterolemia, Hypercholesterolemia
Conditions
Brief summary
The study will assess the safety and tolerability of Ezetimibe 10 mg+ Rosuvastatin 2.5 mg and Ezetimibe 10 mg+ Rosuvastatin 5.0 mg for up to 52 weeks in Japanese participants with hypercholesterolemia uncontrolled with monotherapy of Ezetimibe 10 mg or Rosuvastatin up to 5 mg.
Interventions
DRUGEzetimibe
DRUGRosuvastatin
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Japanese * Outpatient with hypercholesterolemia * Female participant who is of reproductive potential has to agree to remain abstinent or use (or partner use) two acceptable methods of birth control from date of signed informed consent to the 14 days after the last dose of study drug * Will maintain a stable diet that is consistent with the Japan Atherosclerosis Society Guideline 2012 (JAS 2012) for prevention of atherosclerotic cardiovascular diseases for the duration of the study
Exclusion criteria
* Uncontrolled hypertension (treated or untreated) * Uncontrolled type 1 or type 2 diabetes mellitus * Homozygous Familial Hypercholesterolemia or has undergone low-density lipoprotein (LDL) apheresis * Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins * Has had a gastrointestinal tract bypass, or other significant intestinal malabsorption * History of cancer within the past 5 years (except for successfully treated dermatological basal cell or squamous cell carcinoma or in situ cervical cancer) * Human Immunodeficiency Virus (HIV) positive * History of drug/alcohol abuse within the past 5 years or psychiatric illness not adequately controlled and stable on pharmacotherapy * Consumes more than 25 g of alcohol per day * Currently following an excessive weight reduction diet * Currently engages in a vigorous exercise regimen (e.g.; marathon training, body building training etc.) or intends to start training during the study * Hypersensitivity or intolerance to Ezetimibe or Rosuvastatin * Myopathy or rhabdomyolysis with Ezetimibe or any statin * Pregnant or lactating * Taking any other investigational drugs and/or has taken any investigational drugs within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | Up to 2 weeks post last dose of study drug (up to 54 weeks) | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who reported at least 1 AE was summarized. |
| Percentage of Participants Who Had Study Drug Discontinued Due to an AE | up to 52 weeks | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline (predose) and Week 52 | Blood was collected at baseline (predose) and after 52 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by beta quantification ultracentrifugation. The percentage change from baseline at Week 52 was summarized. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe 10 mg + Rosuvastatin 2.5 mg 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 114 |
| Ezetimibe 10 mg + Rosuvastatin 5.0 mg 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. | 21 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Participant Moved | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | Total |
|---|---|---|---|
| Age, Continuous | 58.2 Years STANDARD_DEVIATION 10.8 | 52.4 Years STANDARD_DEVIATION 13.3 | 57.3 Years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 114 Participants | 21 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 61 Participants | 9 Participants | 70 Participants |
| Sex: Female, Male Male | 53 Participants | 12 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 0 / 21 |
| other Total, other adverse events | 53 / 114 | 13 / 21 |
| serious Total, serious adverse events | 2 / 114 | 1 / 21 |
Outcome results
Primary
Percentage of Participants Who Experience at Least 1 Adverse Event (AE)
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who reported at least 1 AE was summarized.
Time frame: Up to 2 weeks post last dose of study drug (up to 54 weeks)
Population: All participants who received at least 1 dose of study drug during treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 72.8 Percentage of Participants |
| Ezetimibe 10 mg + Rosuvastatin 5.0 mg | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) | 76.2 Percentage of Participants |
Primary
Percentage of Participants Who Had Study Drug Discontinued Due to an AE
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized.
Time frame: up to 52 weeks
Population: All participants who received at least 1 dose of study drug during treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Percentage of Participants Who Had Study Drug Discontinued Due to an AE | 0.9 Percentage of Participants |
| Ezetimibe 10 mg + Rosuvastatin 5.0 mg | Percentage of Participants Who Had Study Drug Discontinued Due to an AE | 0.0 Percentage of Participants |
Secondary
Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)
Blood was collected at baseline (predose) and after 52 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by beta quantification ultracentrifugation. The percentage change from baseline at Week 52 was summarized.
Time frame: Baseline (predose) and Week 52
Population: All participants that received at least 1 dose of study drug, had baseline data for those analyses that required baseline data and had post-baseline data for endpoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -33.8 Percentage change |
| Ezetimibe 10 mg + Rosuvastatin 5.0 mg | Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) | -23.9 Percentage change |