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

Cardiovascular Fixed Dose Combination Pill: A Pharmacodynamic Study of a Fixed Dose Combination of Acetylsalicylic Acid, Simvastatin, and Ramipril in Subjects With Elevated LDL Cholesterol

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.

Study Overview

• Status: Terminated
• Conditions: Elevated LDL Cholesterol
• Intervention / Treatment: Drug: Cardiovascular fixed dose combination pill (acetylsalicylic acid, simvastatin and ramipril),; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, NY 10029-6574
      • Mount Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed Dose Combination Pill; 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)	Drug: Cardiovascular 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.
Active Comparator: Simvastatin; Once daily oral dose of Simvastatin 40 mg	Drug: Simvastatin; A once daily oral dose of simvastatin for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 and Day 84 of the Period 1 and Day 126 and Day 210 of Period 2

Collaborators and Investigators

• Sponsor: Ferrer Internacional S.A.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: October 23, 2009
• First Submitted That Met QC Criteria: October 29, 2009
• First Posted (Estimate): October 30, 2009

Study Record Updates

• Last Update Posted (Estimate): August 31, 2012
• Last Update Submitted That Met QC Criteria: July 31, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: dose; cardiovascular; cholesterol; combination; LDL; fixed; pill
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Simvastatin; Ramipril
• Other Study ID Numbers: P-080647-01