Bioavailability Study of Rosuvastatin/Ezetimibe and Nilemdo Versus Nustendi and Crestor in Healthy Subjects Under Fasting Conditions
- Trial ID
- 2023-507048-35-00
- Protocol
- 950/23
- Sponsor
- Adamed Pharma S.A.
Trial statistics
Objectives
The primary objective of this study is to evaluate the **bioavailability** of test products Rosuvastatin/Ezetimibe, tablets, 20 mg/10 mg or Ezehron Duo, 20 mg + 10 mg, tablet, both administered in combination with Nilemdo 180 mg film-coated tablets, compared to reference products Nustendi 180 mg/10 mg film-coated tablets in combination with Crestor, 20 mg, film-coated tablets. This study is conducted in healthy male and female subjects under fasting conditions. The clinical relevance of this objective lies in determining the pharmacokinetic profile of the test formulations, which is crucial for ensuring therapeutic efficacy and safety in clinical use.
Participants
The clinical trial involves a study population comprising **healthy subjects** with an age range categorized as adults. Both male and female participants are included in the trial, and the population selection considers vulnerable groups. However, the sponsor has not provided the total number of participants involved in the study. The trial is a bioavailability study, and as such, it does not focus on a specific medical condition. The selection process for the trial population and any relevant lifestyle considerations, such as diet or physical activity, have not been disclosed by the sponsor. Key inclusion or exclusion criteria are also not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, single-dose, three-period, three-treatment cross-over **bioavailability** study. It aims to compare the test products Rosuvastatin/Ezetimibe tablets, 20 mg/10 mg, or Ezehron Duo, 20 mg + 10 mg, tablet, both administered in combination with Nilemdo 180 mg film-coated tablets, to the reference products Nustendi 180 mg/10 mg film-coated tablets in combination with Crestor, 20 mg, film-coated tablets. The study will be conducted in healthy male and female subjects under fasting conditions. The trial is categorized as a Phase 3 study and is expected to commence recruitment on October 11, 2023, with an estimated end date of November 26, 2023.
Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to assess eligibility based on predefined criteria. Following successful screening, participants will be randomized to receive the study treatments in a cross-over manner across three periods. Each treatment period will be separated by a washout phase to ensure no carryover effects. The study will include follow-up visits to monitor the participants' health and collect necessary data. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.
The expected length of participant involvement in the study is determined by the duration of the treatment periods and the washout phases, which are structured to ensure the integrity of the bioavailability assessments. Participants may be subject to early termination from the study if they experience adverse events, fail to comply with study procedures, or withdraw consent. The study is designed to ensure the safety and well-being of participants while achieving the scientific objectives of the trial.
Treatment
In this clinical trial, the experimental medication and non-experimental treatments have not been specified in the provided data. Therefore, a detailed description of the experimental medication, including its name, pharmaceutical form, dosage, route, and frequency of administration, cannot be provided. Similarly, information regarding any non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatment, is not available.
Due to the lack of specific information, additional relevant details about drug administration, dosing schedules, and participant compliance monitoring are also not included. The absence of data on the experimental and non-experimental treatments limits the ability to provide a comprehensive description of the treatments used in this clinical trial.
Efficacy
The clinical trial is in Phase 3, with an estimated recruitment start date of October 11, 2023, and an estimated end date of November 26, 2023. Efficacy will be assessed through a structured evaluation process, although specific parameters or endpoints for efficacy assessment are not detailed in the provided data. The trial will likely involve systematic data collection and analysis at predetermined timepoints, consistent with standard practices in Phase 3 trials. The methods and tools for measuring efficacy, such as validated scales or laboratory tests, are not specified in the available information. The trial's design and execution will adhere to rigorous scientific standards to ensure the reliability and validity of the efficacy assessments.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Healthy males and non-pregnant and non-breast-feeding females1, ≥18 and ≤ 60 years of age (on the day of Informed Consent Form signing). Caucasian race.
- Non-smoker or past smoker (who has stopped smoking at least 6 months before the first dosing).
- Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2, (on the day of screening).
- Subject is available for the whole study and has provided his/her written informed consent.
- Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (heart rate, systolic and diastolic blood pressure, and body temperature) and 12-lead ECG. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator
- All laboratory screening results within the normal range or deemed clinically insignificant by Investigator
- Acceptance of use of contraceptive measures during the whole study by both female and male subjects2.
- The subject speaks and understands Czech fluently.
Exclusion Criteria
- Acute or chronic diseases and/or clinical finding which may interfere with the aims of the study or with the drug’s safety, tolerability, bioavailability and/or pharmacokinetics of the IMP.
- Use of systemic drugs known to alter hepatic metabolism within 90 days prior to the first dosing.
- Any systemic prescription treatment within 28 days before the first dosing, except hormonal contraceptives or substitution taken without significant changes in dose for 90 days prior to the first dosing.
- Any systemic over-the-counter (OTC) drug treatment and/or vitamins and/or herbal treatment (e.g. Saint John´s Wort) and/or food supplements within 14 days before the first dosing.
- Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or platelets within 14 days before the first dosing.
- Getting a tattoo, body piercing or any cosmetic treatment involving skin penetration within 90 days before the screening unless evaluated by Investigator as non-significant for inclusion in the study.
- Positive results of drugs of abuse in urine at screening and at check-in.
- Positive result of alcohol breath test at screening and at check-in.
- Positive result of urine cotinine test at screening.
- Body temperature is out of the range of 35.7-36.9 °C at screening and at check-in.
- Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 bpm during the screening procedure.
- Existing gastrointestinal diseases, renal or hepatic diseases and/or pathological findings, which might interfere with the drug’s safety, tolerability, absorption and/or pharmacokinetics.
- Any significant clinical abnormality, including a positive result of HBsAg and/or HCV and/or HIV test during screening procedure.
- Anaemia, haemoglobin below 120 g/L for women and 130 g/L for men at screening.
- Positive result of blood pregnancy test at screening or positive urine pregnancy test at check-in or breast-feeding or lack of results of pregnancy test.
- Less than 45 days between exit procedure in previous study and the first dosing in this study.
- History or presence of serious clinical illness that can impact the fate of drugs (their absorption and/or distribution and/or metabolism and/or elimination).
- History or severe allergy or allergic reactions to the study drugs or related drugs (e.g. ACE, dihydropyridine derivates) or any of the excipients.
- Clinically significant illness within 28 days before the first dosing, including major surgery.
- Serious mental disease and/or inability to cooperate with clinical team.
- Orthostatic hypotension in history or during the screening procedure.
- Drug, alcohol (≥ 40 g pure ethanol per day for men or ≥ 20 g pure ethanol per day for women), solvents or caffeine abuse.
- Use of organ-toxic drugs within 90 days before the first dosing (e.g. any drug with a well-defined potential for toxicity to a major organ or system such as chloramphenicol, which may cause bone marrow suppression).
- Active liver disease and/or level of ALT, AST or GGT ≥ 3 x ULN at the screening.
- Creatine kinase (CK) out of normal range unless evaluated by Investigator as non-significant for inclusion in the study.
- Impaired kidney function, clearance of creatinine (MDRD) < 1 mL/s.
- Current or history of skeletal muscles disorders (muscular toxicity, myopathy and rhabdomyolysis) or current skeletal muscles injuries, including a family history of hereditary muscular disorders.
- History or presence of lactose intolerance, galactose intolerance or glucose-galactose malabsorption syndrome.
- Current or history of hypothyreosis.
- Current or history of hyperuricemia or gout.
- Inability to swallow large tablet.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 11 Oct 2023 | 24 |
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 |
|---|---|---|---|---|---|---|
Ezehron Duo, 20 mg + 10 mg, tabletka | Test | TABLETKA | ORAL | 30 | 1 | PRD5995690 |
Nustendi 180 mg/10 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 190 | 1 | PRD8127280 |
Nilemdo 180 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 180 | 1 | PRD8158928 |
Rosuvastatin/Ezetimibe, tablets, 20 mg/10 mg | Test | TABLET | ORAL | 30 | 1 | PRD10568079 |
Crestor, 20 mg, tabletki powlekane | Comparator | TABLETKI POWLEKANE | ORAL | 20 | 1 | PRD397765 |
Heparin Léčiva Injekční roztok | Other | INJEKČNÍ ROZTOK | INTRAVENOUS | 2.1 | 1 | PRD6653638 |