A Pharmacodynamic Study to Evaluate the Effect of a Fixed Dose Combination Pill on Low Density Lipoprotein (LDL) Cholesterol

Phase 2

Terminated

Conditions: Elevated LDL Cholesterol

Interventions: Drug: Cardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin and ramipril),
Drug: Simvastatin

Registration Number: NCT01004705

Lead Sponsor: Ferrer Internacional S.A.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 36

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fixed Dose Combination Pill	Cardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin and ramipril),	Once daily oral dose of combination of acetylsalicylic acid, simvastatin, and ramipril (containing 100 mg acetylsalicylic acid, 40 mg simvastatin, and 5 or 10 mg ramipril)
Simvastatin	Simvastatin	Once daily oral dose of Simvastatin 40 mg

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.