Elevated LDL Cholesterol
Conditions
Keywords
cardiovascular, fixed, dose, combination, pill, LDL, cholesterol
Brief summary
This study evaluates the effect on LDL cholesterol of the 3 drugs given together in the cardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin, and ramipril) as compared to the effect on LDL cholesterol of simvastatin given alone. Approximately 76 subjects will be screened, 60 randomized in order about 52 subjects to finish the study.
Interventions
DRUGCardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin and ramipril),
A once daily oral dose of the cardiovascular fixed dose combination pill ( acetylsalicylic acid, simvastatin, ramipril) for 12 weeks.
DRUGSimvastatin
A once daily oral dose of simvastatin for 12 weeks.
Sponsors
Ferrer Internacional S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥18 years of age * Previously untreated LDL cholesterol ≥100 mg/dL and ≤180 mg/dL. * Provide written informed consent.
Exclusion criteria
* Subjects with a medical condition requiring chronic pharmacological treatment * On direct questioning and physical examination have evidence of any clinically significant chronic disease, including known or suspected human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. * On direct questioning and physical examination have a medical history or evidence of abuse of drugs. * Medical history of gastrointestinal bleeding or gastric or duodenal ulcer. * Systolic pressure ≥140 mmHg or diastolic pressure \>89 mmHg requiring hypotensive medication. * Presence of secondary dyslipidemia. * Previous use of cholesterol lowering medication. * Previous coronary artery bypass graft (CABG). * Previous percutaneous transluminal coronary angioplasty (PTCA) with a drug-eluting stent. * Presence of severe congestive heart failure (New York Heart Classification \[NYHC\] III IV). * Presence of untreated or uncontrolled thyroid disease. * Past or current medical history of asthma or aspirin induced asthma * Previous hypersensitivity to ACE inhibitors (eg angioedema or cough). * Previous hypersensitivity to ARBs. * History of unstable angina. * Serum creatinine \>2 mg/dL. * Creatine phosphokinase (CPK) ≥5 x the upper limit of normal (ULN). * Hemoglobin ≤12 g/dL (120 g/L) for male subjects or ≤10 g/dL (100 g/L) for female subjects. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN. * Total bilirubin ≥1.5 x ULN. * Serum triglyceride concentration ≥400 mg/dL. * Subjects not using effective contraception methods (intra uterine device \[IUD\] and condom or diaphragm with spermicide and condom) during the study and for at least one month thereafter. * Pregnant, lactating, breastfeeding, or intends to become pregnant during the course of the study (females only). All women must have a negative urine pregnancy test at the Screening Visit, be surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or have a postmenopausal status (no menses) for at least one year. * Contraindications to or known or suspected hypersensitivity to aspirin, simvastatin or ramipril or their excipients. * Presence of mental illness limiting the capacity for self-care. * Presence of major systemic illnesses: renal disease, liver disease, neurological or psychiatric disease. * Participation, in the 30 days preceding enrolment into the study, in any other clinical study in which investigational or marketed drugs were employed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in LDL Cholesterol Levels Between the Basal and the Final Visit of Each Treatment Period. | Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2 | Change from baseline in LDL cholesterol level following each Treatment Period was defined as the difference between the measurements from the baseline visit (Visit 4, Day 1) and Visit 9 (Day 84) for Treatment Period 1, and between the Visit 11 (Day 126) and Visit 16 (Day 210) for Treatment Period 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in Mean Total Cholesterol Between the Basal and the Final Visit of Each Treatment Period. | Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2 | Change from baseline in mean total cholesterol level following each Treatment Period was defined as the difference between the measurements from the baseline visit (Visit 4, Day 1) and Visit 9 (Day 84) for Treatment Period 1, and between the Visit 11 (Day 126) and Visit 16 (Day 210) for Treatment Period 2. |
Countries
United States
Participant flow
Recruitment details
126 subjects were screened, 47 met eligibility requirements and 44 entered the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Patients All patients randomized to both study sequences (Combination Pill then Simvastatin and Simvastatin then Combination Pill) | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Randomized Patients |
|---|---|
| Age Continuous | 44.6 years STANDARD_DEVIATION 11.44 |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 22 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 / 44 | 1 / 31 | 2 / 31 |
| serious Total, serious adverse events | 0 / 44 | 0 / 31 | 0 / 31 |
Outcome results
Primary
The Difference in LDL Cholesterol Levels Between the Basal and the Final Visit of Each Treatment Period.
Change from baseline in LDL cholesterol level following each Treatment Period was defined as the difference between the measurements from the baseline visit (Visit 4, Day 1) and Visit 9 (Day 84) for Treatment Period 1, and between the Visit 11 (Day 126) and Visit 16 (Day 210) for Treatment Period 2.
Time frame: Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2
Population: Per Protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Pill | The Difference in LDL Cholesterol Levels Between the Basal and the Final Visit of Each Treatment Period. | -34.24 mg/dL | Standard Deviation 27.103 |
| Simvastatin | The Difference in LDL Cholesterol Levels Between the Basal and the Final Visit of Each Treatment Period. | -27.95 mg/dL | Standard Deviation 32.597 |
Secondary
The Difference in Mean Total Cholesterol Between the Basal and the Final Visit of Each Treatment Period.
Change from baseline in mean total cholesterol level following each Treatment Period was defined as the difference between the measurements from the baseline visit (Visit 4, Day 1) and Visit 9 (Day 84) for Treatment Period 1, and between the Visit 11 (Day 126) and Visit 16 (Day 210) for Treatment Period 2.
Time frame: Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2
Population: Per Protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combination Pill | The Difference in Mean Total Cholesterol Between the Basal and the Final Visit of Each Treatment Period. | -36.81 mg/dL | Standard Deviation 28.715 |
| Simvastatin | The Difference in Mean Total Cholesterol Between the Basal and the Final Visit of Each Treatment Period. | -29.81 mg/dL | Standard Deviation 38.407 |