Bioequivalence Study of Azilsartan Medoxomil 80 mg Tablets (Gedeon Richter Plc., Hungary) and Edarbi® 80 mg Tablets (JSC Nizhpharm, Russia)

NCT06990204 | Not Yet Recruiting Phase 1

• 1 other identifier: EAEU-GCO-AZL-01-2024
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

ACEis are among the most widely used classes of antihypertensive drugs. ARBs have a similar antihypertensive efficacy and protective effect as ACEis, albeit with a somewhat different mechanism for RAS inhibition and a smaller randomized clinical trials' database. A difference between ACEis and ARBs is their tolerability profile, with ARBs having a rate of side effects similar to placebo. Most importantly, the clinical evidence supports a relevant protective role of ARBs toward the CV and renal damage development, as well as the occurrence of major adverse CV events, in hypertensive patients. Moreover, a neutral metabolic effect has been reported upon ARBs administration, in contrast to other antihypertensive agents, such as BBs and diuretics. These properties highlight the use of ARBs as an excellent pharmacological strategy to manage hypertension and its dangerous consequences The purpose of this study is to compare pharmacokinetics (PK), safety, and tolerability of the IMPs Azilsartan medoxomil 80 mg tablets and of Edarbi® 80 mg tablets in healthy adult subjects of both sexes under fasting conditions. Dose proportionality in exposure was established for azilsartan in the azilsartan medoxomil dose range of 20 mg to 320 mg after single or multiple dosing. In the present study the highest available strength of Azilsartan medoxomil 80 mg tablets will be investigated. Administration of this dose is expected to provide accurate and reliable determination of azilsartan plasma concentrations. This is a single center, open label, randomized, four-period, two-sequence, fully replicate, cross-over bioequivalence study in healthy adult subjects of both sexes after single dose administration under fasting conditions. A single oral dose of the IMP (Test IMP: Azilsartan Medoxomil 80 mg tablets or Reference IMP: Edarbi® 80 mg tablets )will be administered under fasting conditions in each of the 4 study periods.

Conditions

Hypertension

Keywords

Hypertension; High Blood Pressure; Azilsartan

Outcome Measures

Primary Outcomes (2)

• Bioequivalence of Azilsartan medoxomil 80 mg tablets and Edarbi® 80 mg tablets by measuring the AUC from time 0 to last collection time t (AUC0-t)

  The primary purpose of the study is to assess the bioequiavelence of Azilsartan medoxomil 80 mg tablets (Gedeon Richter Plc., Hungary) and Edarbi® 80 mg tablets (JSC Nizhpharm, Russia) in healthy adult subjects of both sexes under fasting conditions. The 90% CI for the ratio of geometric means (T/R) based on least-squares means from the ANOVA of the ln-transformed AUC0-t for azilsartan must be within 80.00% to 125.00%.

  The duration of sampling period of 72 hours is sufficient to adequately describe the plasma concentration-time profile of azilsartan. The expected total study duration for each subject will be 26-42 days (considering 1-7 days for Screening).

• Bioequivalence of Azilsartan medoxomil 80 mg tablets and Edarbi® 80 mg tablets by measuring the maximum concentration in plasma (Cmax)

  The primary purpose of the study is to assess the bioequiavelence of Azilsartan medoxomil 80 mg tablets (Gedeon Richter Plc., Hungary) and Edarbi® 80 mg tablets (JSC Nizhpharm, Russia) in healthy adult subjects of both sexes under fasting conditions. 90% CI for the ratio of geometric means (T/R) based on least-squares means from the ANOVA of the ln-transformed Cmax must be within 80.00% to 125.00%.

  The duration of sampling period of 72 hours is sufficient to adequately describe the plasma concentration-time profile of azilsartan. The expected total study duration for each subject will be 26-42 days (considering 1-7 days for Screening).

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From enrollment up to 6 weeks.

Study Arms (2)

Azilsartan medoxomil 80 mg tablets

EXPERIMENTAL

1 Azilsartan medoxomil 80 mg tablet (85.36 mg Azilsartan medoxomil potassium (Azilsartan Kamedoxomil) equivalent to 80 mg Azilsartan medoxomil)

Drug: Azilsartan medoxomil 80 mg tablet

Edarbi® 80 mg tablets

ACTIVE COMPARATOR

1 Edarbi® 80 mg tablet (85.36 mg Azilsartan medoxomil potassium (Azilsartan Kamedoxomil) equivalent to 80 mg Azilsartan medoxomil)

Drug: Edarbi® 80 mg tablets

Interventions

Azilsartan medoxomil 80 mg tablet DRUG

1 tablet of 80 mg of azilsartan medoxomil

Azilsartan medoxomil 80 mg tablets

Edarbi® 80 mg tablets DRUG

1 tablet of 80 mg of azilsartan medoxomil.

Edarbi® 80 mg tablets

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or nonpregnant, nonlactating female volunteers, assessed as healthy by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs (blood pressure, pulse rate, respiratory rate, body temperature) assessment, laboratory tests results (clinical chemistry, hematology, serology, and urinalysis), and cardiac monitoring (12-lead ECG).
• Capable of voluntary, non-coerced provision of signed and dated informed consent form (ICF) prior to any study-specific procedures, which includes compliance with the requirements and restrictions listed in the ICF.
• Aged 18-45 years inclusive at the time of signing the ICF.
• Non-smokers (last episode of smoking or last use of tobacco- or nicotine-containing products more than 6 months prior to Screening, if any).
• Body Mass Index (BMI) 18,5-30 kg/m2 inclusive and weight ≥50 kg and ≤ 120kg.
• A valid (performed in accordance with the Clinical investigational site's standard operating procedures \[SOPs\]) negative SARS CoV 2 test result at Screening and upon each admission to the clinical unit.
• Male volunteers (with the exception of vasectomised males) must be willing and able to use one of the following adequate methods of contraception from the first administration of the IMP until at least 30 days after the last administration of the IMP:
• abstinence from penile-vaginal intercourse;
• barrier contraception, i.e., a male condom plus spermicide (foam, gel, cream) when having penile-vaginal intercourse with a woman of childbearing potential.
• Male volunteers must be willing to refrain from donating sperm from the first administration of the IMP until at least 30 days after the last administration of the IMP.
• Female volunteers of childbearing potential (a woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile) who are using one of the adequate methods of contraception listed below consistently and correctly, must be willing and able to continue the use of the chosen adequate birth control method from 28 days prior to the first administration of the IMP until 28 days or 5 half-lives, whichever takes longer, after the last administration of the IMP in this study:
• barrier contraception i.e., a male condom or female cervical cap plus spermicide (foam, gel, cream);
• vasectomised partner;
• abstinence from penile-vaginal intercourse;
• bilateral tubal occlusion;

You may not qualify if:

• History of, or ongoing allergy/hypersensitivity to any of the study IMPs, or components thereof, or drug or any other allergy.
• Known history or presence of malignant disease.
• History or presence of angioedema, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neuromuscular, psychiatric, auto-immune, or neurological disorders; history or presence of cerebrovascular diseases (including cerebral circulation failure), or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
• Conditions associated with circulating blood volume decrease (including vomiting and diarrhea).
• Any abnormalities in laboratory or instrumental test results which are outside the reference range of the Clinical investigational site.
• Creatinine clearance \<80 mL/min based on the Cockcroft-Gault equation.
• Systolic blood pressure \< 100 mmHg or \> 130 mmHg; diastolic blood pressure \< 70 mmHg or \> 90 mmHg; pulse \< 60 bpm or \> 90 bpm.
• Medical history of surgery on gastrointestinal tract and hepatobiliary system (excluding appendectomy).
• Adherence to special types of diets (such as vegetarian, vegan, with salt restriction within 30 days prior to the first administration of the IMP) and lifestyle (work at night, extreme physical activity).
• Difficulty fasting or consuming standard meals.
• No suitable veins for cannulation or repeated venepuncture.
• Any other condition that is capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the IMP; or interfering with the interpretation of data, as judged by the Investigator.
• Use of any prescribed or nonprescribed medication including herbal remedies, vitamins, and minerals within 14 days prior to the first administration of the IMP or longer if the medication has a long half-life.
• Use of drugs interacting with the IMP (for detailed list of concerned drugs, see Section 8.3.4) within 30 days prior to the first administration of the IMP.
• Females who:

Sponsors & Collaborators

• Gedeon Richter Plc.: lead

Study Sites (1)

LLC Professorskaya klinika

Perm, Perm Krai, 614101, Russia

Location

MeSH Terms

Conditions

Hypertension

Interventions

azilsartan medoxomil; Tablets; azilsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Balázs Lázár, M.D

CONTACT

+36204162804; RA.ctaRichter@richter.hu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 25, 2025
• Study Start: June 6, 2025
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: May 25, 2025

Record last verified: 2025-05

Locations

RU (1)