Bioequivalence Study of Two Formulations of Tablets Aceclofenac 100 mg in Healthy Volunteers Under Fasting Conditions

NCT05339373 | Completed Phase 1

• 1 other identifier: ACFNC-2021
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Airtal ®, 100 mg film-coated tablets) or the test (Aceclofenac, 100 mg film-coated tablets) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (2)

• Cmax of aceclofenac in plasma after administration of the test and the reference products.

  Maximum observed concentration in plasma.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

• AUC0-t of aceclofenac in plasma after administration of the test and the reference.

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration using the linear trapezoidal method.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

Secondary Outcomes (8)

• Tmax of aceclofenac in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

• TLQC of aceclofenac in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

• AUC0-INF of aceclofenac in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

• Residual area of aceclofenac in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

• Time point where the log-linear elimination phase begins (TLIN) of aceclofenac in plasma after administration of the test and the reference. products.

  Time points 0.00 (prior to each drug administration) and 0.15, 0.30, 0.45, 1.00, 1.15, 1.30, 1.45, 2.00, 2.20, 2.40, 3.00, 3.30, 4.00, 5.00, 6.00, 8.00, 10.00, 12.00, 24.00 hours after each drug administration.

Study Arms (2)

Sequence TR

OTHER

18 subjects assigned to the sequence TR will receive a single 100 mg dose of the test product Aceclofenac (1 x 100 mg tablet), marked as T in the sequence, in Period 1 and a single 100 mg dose of the reference product Airtal ® (1 x 100 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Aceclofenac film-coated tablet 100 mg; Drug: Airtal® film-coated tablet 100 mg

Sequence RT

OTHER

18 subjects assigned to the sequence RT will receive a single 100 mg dose of the test product Airtal ® (1 x 100 mg tablet), marked as R in the sequence, in Period 1 and a single 100 mg dose of thetest product Aceclofenac (1 x 100 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Aceclofenac film-coated tablet 100 mg; Drug: Airtal® film-coated tablet 100 mg

Interventions

Aceclofenac film-coated tablet 100 mg DRUG

Aceclofenac is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 100 mg of aceclofenac.

Also known as: The test product

Sequence RT; Sequence TR

Airtal® film-coated tablet 100 mg DRUG

Airtal ® is manufactured by Gedeon Richter- RUS", Russia / Gedeon Richter, Hungary. Each tablet contains 100 mg of aceclofenac.

Also known as: The reference product

Sequence RT; Sequence TR

Eligibility Criteria

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

You may qualify if:

• Healthy european men or women aged between 18 to 45 years
• The written consent of the volunteer to be included in the study
• Verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination
• The results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided)
• Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
• For female:
• the results of the examination of the mammary glands (palpation or mammography) within the normal range according to the data obtained within 12 months before the start of the study;
• non-breastfeeding women;
• negative pregnancy test;
• adherence to reliable methods of contraception for female of childbearing potential: sexual continence, or condom + spermicide, or diaphragm + spermicide, started at least 14 days before the first dose of the study drug; intrauterine contraception is also a reliable method of contraception, installed at least 4 weeks before taking the study drugs in the first period;
• сonsent to use these methods of contraception within 30 days after taking the drug in the second period;
• women who do not use acceptable methods of contraception, if they are considered incapable of childbearing, will also be able to participate in the study: women who have undergone a hysterectomy or tubal ligation, women with a clinical diagnosis of infertility, and women who are in menopause (at least a year without menstruation in the absence of alternative pathologies that may cause the cessation of menstruation);
• in case of using contraceptives (injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems), the latter should be canceled at least 60 days before taking the drug in the first period;
• For male: consent to use a double barrier method of contraception (condom + spermicide) or complete sexual abstinence, as well as consent not to participate in sperm donation during the entire study and 30 days after taking the drug in the second period.
• Subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations.

You may not qualify if:

• burdened allergic history, hypersensitivity to any ACE inhibitors, including aceclofenac or excipients that are part of any of the investigational drugs, or intolerance to these components;
• bronchospasm, urticaria, rhinitis after taking acetylsalicylic acid or other NSAIDs in history (complete or incomplete acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma);
• bleeding or perforation of the gastrointestinal tract associated with the use of NSAIDs in history;
• acute bleeding or diseases accompanied by bleeding in the last 2 months;
• clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood;
• other diseases that, in the opinion of the researcher, may affect the absorption, distribution, metabolism or excretion of both drugs, or increase the risk of negative consequences for the volunteer;
• the presence of mental disorders, including a history;
• surgical interventions on the gastrointestinal tract, with the exception of appendectomy;
• acute infectious diseases that ended less than 4 weeks before taking the drug in the first period;
• dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study;
• clinically significant abnormalities on the ECG, the level of systolic blood pressure (SBP) measured in the sitting position at the time of screening ≤ 100 mm Hg or ≥ 139 mm Hg and / or diastolic blood pressure (DBP) ≤ 70 mm Hg or ≥ 89 mm Hg;
• heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 12 or more than 18 per minute at the time of screening, body temperature below 36.0 ° C or above 37.0 °C at the time of screening;
• the use of injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems and other hormonal contraceptives for 60 days before taking the drug in the first period;
• use of any drugs including herbs and food additives, vitamins that can have a significant effect on the PK of lisinopril or data on the effect of which on the pharmacokinetics of lisinopril are unknown, as well as question the characterization of the volunteer as healthy, less than 14 days before taking the drug in the first period;
• taking known inhibitors or inducers of microsomal liver enzymes (barbiturates, omeprazole, cimetidine, etc.) or antiviral drugs less than 2 months before taking the drug in the first study period;

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• X7 Clinical Research LLC: collaborator

Study Sites (1)

X7 Clinical Research

Saint Petersburg, 194156, Russia

Location

Study Officials

• Evgenia Simonova

  CRO X7 Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 21, 2022
• Study Start: April 15, 2022
• Primary Completion: April 30, 2022
• Study Completion: August 15, 2022
• Last Updated: June 28, 2023

Record last verified: 2022-04

Locations

RU (1)