A Pharmacodynamic Study to Evaluate the Effect of a Fixed Dose Combination Pill on Low Density Lipoprotein (LDL) Cholesterol
Condition: Elevated LDL Cholesterol
Intervention: Cardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin and ramipril),; Simvastatin
Intervention description: A once daily oral dose of the cardiovascular fixed dose combination pill ( acetylsalicylic acid, simvastatin, ramipril) for 12 weeks.; A once daily oral dose of simvastatin for 12 weeks.
Intervention MeSH terms: Aspirin; Ramipril; Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cardiovascular; fixed; dose; combination; pill; LDL; cholesterol

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.
    

Eligibility criteria:

        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.