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

Hypertension Clinical Trial

Official title:

Pharmacodynamic Equivalence Study of Ramipril 10 mg and Atorvastatin 40 mg Administered as a Cardiovascular Fixed Dose Combination Pill AAR as Compared to Monotherapy With the Reference Products Altace® 10 mg and Lipitor® 40 mg

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02791958
• Other study ID #: FCD-PP-1501
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 15, 2016
• Last updated: April 7, 2017
• Start date: March 2016
• Est. completion date: October 2017

Study information

• Verified date: April 2017
• Source: Ferrer Internacional S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 528
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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• Patients treated with BP lowering and / or lipid lowering medication can be included if the medication can be safely withdrawn as per physician's judgment.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.

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Cardiovascular Fixed Dose Combination Pill AAR
A once daily oral dose of the Cardiovascular Fixed Dose Combination Pill AAR (acetylsalicylic acid 100 mg, atorvastatin 40 mg and ramipril 10 mg) for 4 weeks.
• Atorvastatin 40 mg
A once daily oral dose of atorvastatin 40 mg (Lipitor®) for 4 weeks
• Ramipril 10 mg
A once daily oral dose of ramipril 10 mg (Altace®) for 4 weeks

Locations

Country	Name	City	State
United States	Central Alabama Research	Birmingham	Alabama
United States	Meridien Research	Bradenton	Florida
United States	PAB Clinical Research	Brandon	Florida
United States	Punzi Medical Center	Carrollton	Texas
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Clinical Therapeutics Corporation	Coral Gables	Florida
United States	Moonshine Research Center, Inc	Doral	Florida
United States	Riverside Clinical Research	Edgewater	Florida
United States	Nova Clinical Research Center inc	Hialeah	Florida
United States	Dr. John C. Gutleber Weight Loss, Beauty, and Family Practice	Homestead	Florida
United States	Cullen Research, LLC	Houston	Texas
United States	Research Trials Worldwide LLC	Humble	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Westside Center for Clinical Research	Jacksonville	Florida
United States	Health Awareness, Inc.	Jupitor	Florida
United States	The Chappel Group Research	Kissimmee	Florida
United States	Einstein Clinical Research	Lancaster	South Carolina
United States	Sunrise Medical Center	Lauderdale Lakes	Florida
United States	National Research Institute	Los Angeles	California
United States	Louisville Metabolic and Atherosclerosis Research	Louisville	Kentucky
United States	Clinical Trials of America LA, LLC	Monroe	Louisiana
United States	Central Texas Health Research	New Braunfels	Texas
United States	DelRicht Research	New Orleans	Louisiana
United States	Clinical Research Source	Perrysburg	Ohio
United States	Deleon Research, PLLC	Plano	Texas
United States	Progressive Medical Research	Port Orange	Florida
United States	Clinical Trials Research	Sacramento	California
United States	Diagnostics Research Group	San Antonio	Texas
United States	Physician PrimeCare Research Institute, PLLC dba H	San Antonio	Texas
United States	Sylvana Research	San Antonio	Texas
United States	Chysalis Clinical Research	St. George	Utah
United States	Meridien Research	St. Petersburg	Florida
United States	Clinical Trials Investigators, Inc	Tustin	California
United States	Bay State Clinical Trials, Inc	Watertown	Massachusetts
United States	Infoshpere Clinical Research, Inc	West Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Ferrer Internacional S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in the adjusted mean 24-h systolic blood pressure results using ABPM between the baseline (week 0) and the final visit (week 8).		Measures at baseline visit (week 0) and final visit (week 8).
Primary	Difference in LDL cholesterol levels between the baseline (week 4) and the final visit (week 8).		Measures at baseline visit (week 4) and final visit (week 8).
Secondary	Difference in the adjusted mean 24-h diastolic blood pressure results (using ABPM) between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in the adjusted mean 24-h mean arterial pressure results (using ABPM) between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in the adjusted mean 24-h heart rate results (using ABPM) between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in Very Low-Density Lipoprotein (VLDL) cholesterol levels between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in HDL cholesterol levels between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in total cholesterol levels between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Difference in triglyceride levels between the basal and the final visits.		Measures at baseline visit (week 0) and final visit (week 8).
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	AEs, clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), vital signs, electrocardiogram (ECG), and physical examination.; The total number of patients with at least one AE and the number of AEs will be included in listings and tabulations. AEs will be coded using MedDRA, classified by system organ class (SOC) and preferred term and tabulated by intensity and causal relationship for each treatment.	Through study completion, an average of 3 months.