Open-label Randomized Crossover Two Period Single Dose Bioequivalence Study of Two Formulations Aceclofenac Tablets 100 mg (Pharmtechnology LLC, Republic of Belarus) and Airtal® Tablets 100 mg (Gedeon Richter- RUS", Russia / Gedeon Richter, Hungary; MA Holder: Almiral S.A., Spain) in Healthy Volunteers Under Fasting Conditions
Overview
- Phase
- Phase 1
- Intervention
- Aceclofenac film-coated tablet 100 mg
- Conditions
- Bioequivalence
- Sponsor
- Pharmtechnology LLC
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- AUC0-t of aceclofenac in plasma after administration of the test and the reference.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Detailed Description
This is an open-labeled, randomized, two period, crossover, a single-center, comparative, single-dose study, in which 36 healthy adult subjects will receive one of the study treatments during each study period. The objective of this study is to determine the bioequivalence of two different formulations of aceclofenac after a single oral dose administration under fasting conditions. Subject eligibility for this study will be determined at the screening visit and eligible subjects will be admitted to the clinical research unit at least 12 hours prior to drug administration for each study period. Hospitalization in the first period of the study will last no more than 37 hours, after which, in the absence of indications for an extension of hospitalization, each subject will be released home; after that, the first period of the study will be completed. The procedures of the second study period will be identical to the first period. After completing all the procedures of the second study period, each subject will undergo a final examination, after which, in case of the absence of adverse events and indications for prolonging hospitalization, the study for the subjects will be considered completed. The total duration of the study for the subject will be no more than 22 days. Eligible subjects will be randomized to one of two treatment sequences. There will be two sequences in the study: TR and RT, where T = the test product, R = the reference product. For each study period, subjects will receive a single 100 mg oral dose of aceclofenac (the test or the reference formulation). Study participants will be aware they will receive different formulations of the same drug, without being informed which product (Test or Reference) is being administered. For each subject, all scheduled postdose activities and assessments will be performed relative to the time of study drug administration. Fasting will continue for at least 4 hours following drug administration, after which a standardized lunch will be served. Next meals will be provided for subjects in 6 hours, 9 hours and 12 hours after drug administration. Water will be provided as needed until 1 hour predose. Water will be allowed beginning 2 hours after the administration of the drug. A total of 20 blood samples will be collected (one tube of 6 mL each) in each study period for pharmacokinetic (PK) assessments. The first blood sample will be collected prior to drug administration while the others will be collected up to 24 hours after drug administration. Aceclofenac plasma concentrations will be measured according to a validated bioanalytical method. Statistical analysis of all PK parameters will be based on an ANOVA model. Two-sided 90% confidence interval of the ratio of geometric LSmeans obtained from the ln-transformed PK parameters will be calculated. Statistical inference of aceclofenac will be based on a bioequivalence approach using the following standards: the ratio of geometric LSmeans with corresponding 90% confidence interval calculated from the exponential of the difference between the Test and the Reference for the ln-transformed parameters Cmax and AUC0-t should all be within the 80.00 to 125.00% bioequivalence range.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
Sequence TR
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.
Intervention: Aceclofenac film-coated tablet 100 mg
Sequence TR
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.
Intervention: Airtal® film-coated tablet 100 mg
Sequence RT
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.
Intervention: Aceclofenac film-coated tablet 100 mg
Sequence RT
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.
Intervention: Airtal® film-coated tablet 100 mg
Outcomes
Primary Outcomes
AUC0-t of aceclofenac in plasma after administration of the test and the reference.
Time Frame: 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.
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration using the linear trapezoidal method.
Cmax of aceclofenac in plasma after administration of the test and the reference products.
Time Frame: 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.
Maximum observed concentration in plasma.
Secondary Outcomes
- 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.)
- λZ 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.)
- Terminal elimination half-life (Thalf) 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.)
- Number of treatment-emergent adverse events for 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.)