Bioequivalence of a fixed‑dose combination of acetylsalicylic acid, atorvastatin and ramipril versus separate tablets in healthy adult volunteers

1 1 1 1

What is this study about?

The study looks at medicines that are commonly used to lower high cholesterol, lower high blood pressure, and reduce the risk of heart disease. The test product is a single capsule that contains three active ingredients: atorvastatin (a cholesterol‑lowering drug), ramipril (a blood‑pressure medication), and acetylsalicylic acid (a low‑dose aspirin that helps prevent blood clots). These same three medicines are also available as separate tablets, which are taken together in current practice.

The purpose of the study is to see whether the single capsule provides the same amount of each medicine in the bloodstream as taking the three separate tablets. Healthy volunteers will receive the combined capsule on one visit and the three individual tablets on another visit, each time after a short fast (no food before taking the medicine). Small blood samples will be taken after each dose to measure how much of each drug appears in the blood, which shows whether the two ways of taking the medicines are equivalent. The study follows a random order of dosing and includes several repeat visits to ensure reliable results.

1 enrollment and screening

after you agree to join the study, you will complete a consent form and undergo basic health checks, including medical history, physical examination, and laboratory tests to confirm that you are a healthy volunteer.

2 fasting before each dosing period

you must not eat or drink anything except water for at least ten hours before each time you take the study medication. this ensures that food does not affect the measurement of the drugs in your blood.

3 first dosing period

you will receive either the test polypill or the reference tablets according to the random assignment. the test polypill is a hard capsule that contains 100 mg atorvastatin, 100 mg acetylsalicylic acid (aspirin), and 10 mg ramipril. the reference tablets consist of three separate tablets: one aspirin 100 mg tablet, one atorvastatin 80 mg film‑coated tablet, and one ramipril 10 mg tablet. you will swallow the medication(s) with a small amount of water once, under fasting conditions.

4 blood sampling after first dose

shortly before you take the medication, a baseline blood sample will be drawn. after the dose, additional blood samples will be collected at several time points (for example, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours) to measure the levels of atorvastatin, aspirin, and ramipril in your bloodstream.

5 washout period

after the first series of blood draws, you will have a washout period during which no study medication is taken. this interval allows the drugs to be cleared from your body before the next dosing period.

6 second dosing period

you will receive the opposite formulation from the first period. if you took the test polypill first, you will now take the three reference tablets, and vice versa. the same single oral dose (100 mg atorvastatin, 100 mg aspirin, 10 mg ramipril) will be administered under fasting conditions.

7 blood sampling after second dose

blood samples will be collected at the same time points as in the first period to compare drug levels between the two formulations.

8 third dosing period (first replication)

the study design includes a replication of each formulation. you will again receive the same formulation that was given in the first period, following the same fasting and single‑dose procedure.

9 blood sampling after third dose

the same series of blood draws will be performed to obtain a second set of measurements for the first formulation.

10 fourth dosing period (second replication)

you will receive the same formulation that was given in the second period, again under fasting conditions and as a single oral dose.

11 blood sampling after fourth dose

final blood samples will be taken at the same scheduled times to complete the data set for the second formulation.

12 final assessment and study completion

after the last blood draw, a final medical check will be performed. any remaining study documentation will be completed, and you will be informed that your participation in the trial has ended.

Who Can Join the Study?

Must be a male or female, healthy volunteer who is older than 18 years.
Must avoid eating or drinking grapefruit, Seville orange, or pomelo (including juices) for 72 hours before and 72 hours after taking the study medication.
Must be able to understand the study’s purpose, possible risks, and follow all study instructions.
Must give a written, voluntary consent before any screening procedures.
For women only: must not be breastfeeding (non‑lactating).
For women only: must have a negative result on a pregnancy test.
For women only: must use an effective non‑hormonal method of contraception (condoms, intra‑uterine device, sponge, diaphragm, or a combination) or abstain from sex from screening until the follow‑up visit or three weeks after treatment, whichever is longer.
Must have a negative COVID‑19 test.
Must have a Body Mass Index (BMI) between 18.5 and 30.0 kg/m² (a measure of weight relative to height).
Must have normal blood counts (haematology), blood chemistry (clinical chemistry), and urine tests (urinalysis); small differences that are not clinically important are allowed.
Must have no kidney problems (renal impairment) and no liver problems (hepatic impairment).
Must have no heart diseases (cardiovascular) or serious lung diseases (respiratory).
Must have no current or past infectious disease that is acute (sudden) or chronic (long‑lasting).
Must be a non‑smoker or have quit smoking for at least two years before the study.
Must avoid alcohol for 48 hours before and 72 hours after taking the study medication.
Must avoid foods or drinks containing methylxanthines (such as coffee, tea, cola, energy drinks, chocolate), St John’s Wort, and chewing gum for 48 hours before and 72 hours after taking the study medication.

Who Cannot Join the Study?

Allergy to any of the study medicines, medicines that are similar, or any of the inactive ingredients in the pills.
Haemophilia (a blood‑clotting disorder known as type A, B, or C).
History of serious stomach bleeding, a hole in the stomach, or having had part or all of the stomach removed.
History of achlorhydria (no stomach acid) or surgery that bypasses or removes the first part of the small intestine called the duodenum.
Significant disease of the gallbladder or bile ducts, liver tumors, or any liver function problems.
Chronic inflammatory bowel disease such as Crohn’s disease or ulcerative colitis.
Heart rate below 60 or above 100 beats per minute, body temperature below 35.5 °C or above 37.4 °C, breathing rate below 14 or above 20 breaths per minute, or blood pressure lower than 90/50 mmHg or higher than 140/90 mmHg at the screening visit.
Abnormal heart test results (ECG) that are considered clinically important.
Creatine phosphokinase (an enzyme that shows muscle damage) more than five times the normal upper limit.
AST or ALT (liver enzymes) more than three times the normal upper limit.
Blood potassium level higher than the normal range.
Rare inherited problems that affect how the body handles sugar, such as lactase deficiency (cannot digest lactose), glucose‑galactose malabsorption, or gluten intolerance (celiac disease).
Significant narrowing of both kidney arteries or narrowing of the kidney artery when only one kidney is working.
Active viral infection within the past four weeks.
Vaccination within the past two weeks.
Any drug or alcohol abuse, recent psychiatric disorder, or use of medicines that affect the mind within the last two years.
Any condition that could change how the study medicines are absorbed, moved, broken down, or removed from the body.
Any current acute (sudden) or chronic (long‑lasting) infection.
Positive test for HIV, hepatitis B, or hepatitis C.
Being vegetarian or following a special diet that requires long periods without eating.
History of difficulty donating blood.
Difficulty swallowing solid tablets or capsules.
Participation in another clinical study with a new investigational drug in the past three months or with a generic drug in the past two months.
Known or suspected inability to follow study rules, unreliability, inability to understand study information, or financial circumstances that could affect the decision to join.
Hospital stay for any reason within eight weeks before the study starts.
Planned hospitalization within three months after the last dose of the study drug.
Donation of 450 ml or more of blood within eight weeks before the study, or donation of plasma within 14 days before the study.
Taking any prescription or over‑the‑counter medication during the two weeks before the study or while in the study.
History or presence of any serious medical condition such as cancer, major kidney, liver, stomach, lung, heart, hormone, bone, blood, or nerve disorders, or any metabolic or blood disorder.
History or current presence of clotting problems, such as blood clots in arteries or veins, pulmonary embolism (clot in the lungs), deficiency of clotting factors, stroke, chest pain (angina), heart attack, coronary artery disease, or porphyria (a rare blood disorder).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

No sites found in this category

Other Sites

Site Name	City	Country	Status
3y Ptzgrjbmhizfodc Cjgieoovrbxt &ioep Rarr Szyhnd	Cumparatura	Romania

Trial status

Country	Status	Recruitment Start
Romania	Not recruiting	15.09.2023

Trial locations

Investigated Drugs:

Cardyl is a film‑coated tablet that contains atorvastatin. Atorvastatin belongs to a group of medicines called statins, which are used to lower cholesterol and reduce the risk of heart disease. In this study, Cardyl was given as one of the separate reference medicines to compare with the combined pill.

Aspirin N is a tablet that contains acetylsalicylic acid, commonly known as aspirin. Aspirin helps prevent blood clots by making the blood less likely to clot, which can lower the chance of heart attacks and strokes. In the trial, Aspirin N was taken together with the other reference tablets to represent the standard treatment.

Acovil is a tablet that contains ramipril. Ramipril is an ACE‑inhibitor that relaxes blood vessels, helping to lower blood pressure and protect the heart. In this study, Acovil was used as the individual reference medicine for the blood‑pressure component.

Cardiovascular Pill AAR is a hard‑capsule polypill that combines three medicines—atorvastatin, ramipril, and acetylsalicylic acid—into one single dose. This combined pill is intended to lower cholesterol, reduce blood pressure, and prevent blood clots all at once. In the trial, the polypill was the test product whose overall effect and absorption were compared to taking the three separate reference tablets together.

Hypercholesterolemia – A condition where the blood contains high levels of cholesterol, especially low‑density lipoprotein (LDL). Over time, excess cholesterol can deposit in the walls of arteries, forming fatty streaks. These streaks gradually enlarge into plaques that narrow the vessel lumen. As plaques grow, blood flow to organs can become restricted. The disease often develops silently and may only be detected through blood tests.

Hypertension – Persistent elevation of the pressure within the arterial blood vessels. The increased pressure forces the heart to work harder, which can cause the heart muscle to thicken. The arterial walls may become stiffer, further raising blood pressure. Over many years, the strain can affect the kidneys, eyes, and brain. The condition usually progresses without obvious symptoms until complications arise.

Atherosclerotic cardiovascular disease – A disorder in which plaques made of fat, cholesterol, and cellular debris build up inside the arteries. The plaques can slowly narrow the vessels, limiting blood flow to the heart, brain, or limbs. Occasionally, a plaque may rupture, leading to a clot that blocks the artery completely. This blockage can cause a heart attack, stroke, or limb ischemia. The disease advances over many years and is often silent until an acute event occurs.

Trial ID:

2023-505572-30-00

Protocol code:

ARA-BESD-14-FRI/23

Trial Phase:

Human Pharmacology (Phase I) – Bioequivalence Study

Other Trials to Consider

#1 Clinical Trials Search in Europe

Bioequivalence of a fixed‑dose combination of acetylsalicylic acid, atorvastatin and ramipril versus separate tablets in healthy adult volunteers

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?