Bioequivalence Study of Polypill AAR 100/80/10 mg Versus Aspirin 100 mg, Cardyl 80 mg, and Acovil 10 mg in Healthy Volunteers Under Fasting Conditions
- Trial ID
- 2023-505572-30-00
- Protocol
- ARA-BESD-14-FRI/23
- Sponsor
- Ferrer Internacional S.A.
Trial statistics
Objectives
The primary objective of this study is to evaluate the **bioequivalence** of Polypill AAR 100/80/10 mg capsules, a fixed-dose combination, compared to the coadministered reference formulations of Aspirin® N 100 mg tablets, Cardyl® 80 mg film-coated tablets, and Acovil® 10 mg tablets. This assessment is conducted in healthy male and female volunteers under fasting conditions. Establishing bioequivalence is clinically relevant as it ensures that the test formulation has similar bioavailability to the reference formulations, which is crucial for ensuring therapeutic efficacy and safety in patients.
Participants
The clinical trial involves a study population of **healthy volunteers** comprising both male and female participants. The age range of the participants falls between 18 to 65 years, indicating a focus on adult individuals. The trial does not include a vulnerable population, ensuring that the participants are not at increased risk due to their health status. The sponsor has not provided information regarding the total number of participants involved in the study. The selection of the trial population is based on the inclusion of healthy individuals, without specific lifestyle considerations such as diet or physical activity being highlighted. The absence of detailed inclusion or exclusion criteria suggests a broad approach to participant selection within the defined age and health parameters.
Plans and Procedures
The clinical trial is designed as an **open-label**, four-period, two-sequence, fully-replicated, randomized, single-dose comparative study. The primary objective is to assess the bioequivalence of Polypill AAR 100/80/10 mg capsules, a fixed-dose combination, compared to equal doses of coadministered Aspirin® 100 mg tablets, Cardyl® 80 mg film-coated tablets, and Acovil® 10 mg tablets in healthy male and female volunteers under fasting conditions. The trial is categorized as a Phase 2 study and is expected to run from September 15, 2023, with an estimated end date of December 31, 2023.
Participants will undergo a sequence of study visits, beginning with an inclusion visit, which serves as the screening phase to determine eligibility based on predefined criteria. Following successful screening, participants will be randomized into one of the two sequences for the administration of the test and reference formulations. The study involves four periods, during which participants will receive single doses of the test and reference formulations in a crossover manner. Each period will be separated by a washout phase to ensure no carryover effects between treatments. Follow-up visits will be scheduled to monitor the participants' health and collect necessary data for bioequivalence analysis. The end-of-study visit will conclude the trial, where final assessments will be conducted to ensure participant safety and gather any remaining data.
The expected length of participant involvement is approximately three and a half months, encompassing the screening, treatment, and follow-up phases. Conditions that may lead to early termination from the study include adverse events, non-compliance with study procedures, or withdrawal of consent by the participant. The study is conducted on healthy volunteers, and the inclusion and exclusion criteria are designed to ensure the safety and integrity of the trial outcomes.
Treatment
The clinical trial documentation does not provide specific details regarding the **experimental medication** used in the study. Information such as the name, pharmaceutical form, dosage, route, and frequency of administration is not available. Additionally, there is no data on whether the medication is a **paediatric formulation** or if it is classified as an **orphan drug**. The maximum daily dose, total dose, and treatment period are also unspecified.
Details about any **non-experimental treatments** used in the study, such as standard-of-care therapy, placebo, or comparator treatment, are not provided. There is no information on the administration of other medicinal products or their role in the trial.
Furthermore, the documentation lacks information on the **participant compliance monitoring** procedures, dosing schedules, and any additional relevant information about drug administration. The absence of these details limits the ability to provide a comprehensive description of the treatments involved in the clinical trial.
Efficacy
The clinical trial is designed to assess efficacy through a structured evaluation process. As the trial is in Phase 2, it focuses on determining the effectiveness of the intervention in a specific patient population. The trial is scheduled to commence recruitment on September 15, 2023, with an estimated end date of December 31, 2023. Although specific efficacy parameters such as primary and secondary endpoints are not detailed, typical Phase 2 trials often involve measuring symptom improvement, biomarker levels, or disease remission rates. The methods for measuring and analyzing these parameters are typically standardized and may include validated scales, laboratory tests, or patient-reported outcomes. The trial will likely involve periodic assessments at predetermined timepoints to monitor changes and gather data for analysis. The results will contribute to understanding the intervention's efficacy and inform subsequent trial phases.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female, healthy volunteers, older than 18 years of age
- Subject with a Body Mass Index ≥18.5 and ≤ 30.0 Kg/m2
- Normal haematology, clinical chemistry and urinalysis (small deviations outside the normal limits are acceptable providing the values are not considered clinically significant)
- Absence of renal and hepatic impairment
- Absence of cardiovascular and severe respiratory diseases
- Absence of any acute or chronic infectious disease
- Non-smokers or ex-smokers that gave up smoking for at least two years prior to the study
- The subject agrees to abstain from alcohol for 48 hours prior to study drug administration and during the experimental period (72 hours after the IMP administration)
- The subject agrees to abstain from beverages or food containing methylxanthines (coffee, tea, cola, energy drinks, chocolate etc.), St John’s Wort and chewing-gum for 48 hours prior to study drug administration and during the experimental period (72 hours after the IMP administration)
- The subject agrees to abstain from beverages or food containing grapefruit, seville oranges, and pomelo fruits or juices for 72 hours prior to study drug administration and during the experimental period (72 hours after the IMP administration)
- Ability to understand the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the Clinical Investigator and to comply with the requirements of the entire study
- Informed written consent given voluntarily before the initiation of the study screening
- For female subjects only: non-lactating status
- For female subjects only: negative results to the pregnancy test
- For female subjects only: use of effective non-hormonal method of contraception (condoms, intra-uterine device, sponge, diaphragm or a combination of these) or abstinence starting from screening and until follow-up examination or 3 weeks after treatment, whichever is longer
- Negative result to the COVID19 test
Exclusion Criteria
- History of hypersensitivity to the test drugs or to drugs belonging to the same pharmacological and chemical classes or to the inactive ingredients of the formulations
- Subjects with rare hereditary problems of glucose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, gluten intolerance
- Participation in a clinical study with a new investigational product in the preceding three months or in a clinical study with a generic product in the preceding two months
- Hospitalization for any reason within eight weeks prior to the study initiation
- Subjects intends to be hospitalized within 3 months after last study drug administration
- Donation of 450 ml or more of blood, within eight weeks prior to the study initiation or donation of plasma within 14 days prior to study initiation
- Intake of any prescription or non-prescription drugs during the two weeks preceding the study or throughout the study
- History or presence of any relevant medical condition including cancer, significant disease of the renal, hepatic, gastrointestinal, respiratory, cardiovascular, endocrine or locomotor systems, and any metabolic, haematological (see also exclusion criteria 9 and 10) or neurological disorder
- History or actual presence of coagulation disorders such as thromboembolic diseases (e.g. arterial or venous thrombophlebitis, pulmonary embolism or coagulation factors deficiency), cerebrovascular diseases, angina pectoralis, myocardial infarction or coronary arterial disease, porphyria
- Haemophilia (A or B or C)
- History of gastrointestinal bleeding or perforation; history of partial or total gastrectomy
- Subjects with history of achlorhydria or who have had surgery that bypasses or excludes the duodenum
- History of significant gallbladder/ biliary tract disease, liver tumors or any liver function disorders
- Chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
- Subject with heart rate outside the range of 60-100 beats per minute or a body temperature outside the normal range of 35.5-37.4 °C or a respiratory rate outside the normal range of 14-20 breaths per minute or a sitting blood pressure less than 90/50 mmHg or more than 140/90 mmHg at the screening examination
- ECG evidence of clinically significant abnormalities at the screening examination
- Creatine phosphokinase levels elevated >5 times upper normal limit at screening
- AST and ALT levels elevated >3 times upper normal limit at screening
- Potassium levels higher than normal values at screening
- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney
- Active virus infection during previous 4 weeks
- Immunization during previous 2 weeks
- Any recent history (within the last two years) of drug or alcohol abuse, recent psychiatric disorder or use of psychotropic medicines
- History or any current condition or other disease known to interfere with the absorption, distribution, metabolism or excretion of investigational medicines
- Presence of any acute or chronic infectious disease
- Positive results to the HIV, hepatitis C or hepatitis B tests
- Subject is vegetarian or follows particular diets (especially diets requiring prolonged fasting)
- A history of difficulty with donating blood
- Difficulty in swallowing solids like tablets/capsules
- Subject who is known or suspected not to comply, not reliable, not capable of understanding the information related to risks and discomfort or in such a precarious financial situation that this may influence the decision to participate
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Romania | Not Recruiting | 15 Sept 2023 | 56 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Cardyl 80 mg comprimidos recubiertos con película | Comparator | COMPRIMIDOS RECUBIERTOS CON PELÍCULA | ORAL | 100 | 2 | PRD9994596 |
Aspirin® N 100 mg Tablette AcetylsalicylsäurePh.Eur. | Comparator | TABLETTE | ORAL | 100 | 1 | PRD413851 |
Cardiovascular Pill AAR | Test | HARD CAPSULES | ORAL | 100 | 2 | PRD9192304 |
Acovil 10 mg comprimidos | Comparator | COMPRIMIDOS | ORAL | 10 | 1 | PRD485274 |