Pharmacodynamic Equivalence of Ramipril 10 mg and Atorvastatin 40 mg Administered as a Cardiovascular (CV) Polypill Acetylsalicylic Acid-Atorvastatin-Ramipril (AAR) as Compared to Monotherapy

Ferrer

Status and phase: Unknown; Phase 2

Conditions: Hypertension

Treatments: Drug: Atorvastatin 40 mg; Drug: Ramipril 10 mg; Drug: Cardiovascular Fixed Dose Combination Pill AAR

Study type: Interventional

Funder types: Industry

Identifiers

NCT02791958

FCD-PP-1501

Details and patient eligibility

About

This study is to compare the pharmacodynamics of a Fixed Dose Combination Pill AAR (acetylsalicylic acid 100 mg, atorvastatin 40 mg and ramipril 10 mg) and the respective reference products, atorvastatin (Lipitor®) 40 mg and ramipril (Altace®) 10 mg.

Enrollment: 528 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients aged ≥18 and <75 years.
• Patients with Stage 1 (SBP/DBP: 140-159/90-99 mmHg) or Stage 2 (SBP/DBP: ≥160/≥100 mmHg) hypertension, either untreated or after a wash out period.
• Patients with an LDL cholesterol level of ≥100 mg/dL and, either untreated or after the wash out period.
• Patients untreated with BP lowering and / or lipid lowering medication
• Patients treated with BP lowering and / or lipid lowering medication can be included if the medication can be safely withdrawn as per physician's judgment.
• Provide written informed consent.

Exclusion criteria

• Patients with a BMI of > 35

• SBP < 140 mmHg and DBP < 90 mmHg

• Severe hypertension defined as SBP > 180 mmHg and Diastolic Blood Pressure (DBP) > 110 mmHg

• LDL cholesterol level of <100 mg/dL, either untreated or after the wash out period.

• Serum triglyceride concentration ≥400 mg/dL, either untreated or after the wash out period.

• Patients with a medical condition requiring the chronic pharmacological treatments listed below:

  • Cytochrome P450 3A4 (CYP3A4) inhibitors (eg itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone).
  • Non-steroidal anti-inflammatory drugs (NSAIDs).
  • K-sparing diuretics.
  • Lithium.
  • Amiodarone and verapamil.
  • Oral anticoagulants (eg, warfarin).
  • Steroids.
  • Digoxin.
  • Gemfibrozil.
  • Niacin.
  • Potassium supplements.
  • Cyclosporine.
  • Danazol.
  • Rifampicin.

• Evidence of any known clinically significant chronic disease

• Patients with renal impairment with Creatinine Clearance (CrCl) < 40 mL/ min/ 1.73 m2

• Creatine phosphokinase (CPK) ≥5 x the upper limit of normal (ULN).

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x ULN.

• Total bilirubin ≥1.5 x ULN

• Medical history or evidence of drug or alcohol abuse.

• Medical history of gastrointestinal bleeding or gastroduodenal ulcer.

• Presence of secondary dyslipidemia.

• For patients on antihypertensive and/ or cholesterol lowering medication impossibility to withdraw it safely as per physician's judgment

• 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).

• Prior history of stroke, Transient Ischemic Attack (TIA), Myocardial Infarction (MI), and cardiomyopathy with systolic dysfunction (prior documented Left Ventricular Ejection Fraction (LVEF) < 40%)

• Aspirin induced asthma

• Previous intolerance and/or hypersensitivity to ACE inhibitors, statins and/or salicylates.

• Presence of unstable angina.

• Lab values other than specified out of the central laboratory normal range considered clinically significant.

• Patients and their partners not using effective contraception methods (i.e. intra uterine device (IUD) and condom or diaphragm with spermicide and condom) during the study and for at least one month thereafter, oral contraceptives are allowed.

• 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.

• 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.

• Any other medical condition that in the investigators opinion may interfere with the study procedures and/or evaluations.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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528 participants in 3 patient groups

CV Fixed Dose Combination Pill AAR

Experimental group

Description:

Cardiovascular Fixed Dose Combination Pill AAR (acetylsalicylic acid 100 mg, atorvastatin 40 mg and ramipril 10 mg).

Treatment:

Drug: Cardiovascular Fixed Dose Combination Pill AAR

Atorvastatin

Active Comparator group

Description:

Atorvastatin 40 mg (Lipitor®).

Treatment:

Drug: Atorvastatin 40 mg

Ramipril

Active Comparator group

Description:

Ramipril 10 mg (Altace®).

Treatment:

Drug: Ramipril 10 mg