Clinical trial NCT02791958: 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
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hypertension
Lead sponsor: Ferrer Internacional S.A.
Sponsor class: INDUSTRY
First posted: 2016-06-07
Enrollment: 528
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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* Patients treated with BP lowering and / or lipid lowering medication can be included if the medication can be safely withdrawn as per physician's judgment.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

Primary outcomes:
measure: Difference in the adjusted mean 24-h systolic blood pressure results using ABPM between the baseline (week 0) and the final visit (week 8).
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in LDL cholesterol levels between the baseline (week 4) and the final visit (week 8).
timeFrame: Measures at baseline visit (week 4) and final visit (week 8).
Secondary outcomes:
measure: Difference in the adjusted mean 24-h diastolic blood pressure results (using ABPM) between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in the adjusted mean 24-h mean arterial pressure results (using ABPM) between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in the adjusted mean 24-h heart rate results (using ABPM) between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in Very Low-Density Lipoprotein (VLDL) cholesterol levels between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in HDL cholesterol levels between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in total cholesterol levels between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Difference in triglyceride levels between the basal and the final visits.
timeFrame: Measures at baseline visit (week 0) and final visit (week 8).
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Through study completion, an average of 3 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: Tustin
country: United States
facility: Clinical Trials Investigators, Inc
state: California
city: West Hills
country: United States
facility: Infoshpere Clinical Research, Inc
state: California
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Doral
country: United States
facility: Moonshine Research Center, Inc
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Nova Clinical Research Center inc
state: Florida
city: Homestead
country: United States
facility: Dr. John C. Gutleber Weight Loss, Beauty, and Family Practice
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jupitor
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Kissimmee
country: United States
facility: The Chappel Group Research
state: Florida
city: Lauderdale Lakes
country: United States
facility: Sunrise Medical Center
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: St. Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research
state: Kentucky
city: Monroe
country: United States
facility: Clinical Trials of America LA, LLC
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Watertown
country: United States
facility: Bay State Clinical Trials, Inc
state: Massachusetts
city: Perrysburg
country: United States
facility: Clinical Research Source
state: Ohio
city: Lancaster
country: United States
facility: Einstein Clinical Research
state: South Carolina
city: Carrollton
country: United States
facility: Punzi Medical Center
state: Texas
city: Houston
country: United States
facility: Cullen Research, LLC
state: Texas
city: Humble
country: United States
facility: Research Trials Worldwide LLC
state: Texas
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: Plano
country: United States
facility: Deleon Research, PLLC
state: Texas
city: San Antonio
country: United States
facility: Physician PrimeCare Research Institute, PLLC dba H
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research
state: Texas
city: St. George
country: United States
facility: Chysalis Clinical Research
state: Utah
Study officials:
affiliation: Health Awareness, Inc
name: Ronald Surowitz
role: PRINCIPAL_INVESTIGATOR
References: