Clinical trial NCT04941196: Bioequivalence Study of Anplag® 90mg (Ticagrelor) Tablet & Brilinta® 90 mg (Ticagrelor) Tablet in Healthy Adult Male Pakistani Subjects Under Fasting Condition
Official title: A Single Centre, Cross-over, Single Dose, Two Period, Randomized, Open Label Bioequivalence Study of Anplag® 90mg (Ticagrelor) Tablet With Brilinta® 90 mg (Ticagrelor) Tablet in Healthy Adult Male Pakistani Subjects Under Fasting Condition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Individuals
Keywords: Bioequivalence Study
Pakistani Population
Bioavailability comparison
Lead sponsor: University of Karachi
Sponsor class: OTHER
Collaborators: name: PharmEvo Private Limited., Pakistan
First posted: 2021-06-28
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: single centre, cross over, single dose, two period, randomized, open label Bioequivalence Study
Primary purpose: OTHER

Brief summary: Single oral administration of study drugs (i.e. Anplag® \& Brilinta®) in Two periods after at least 10 hours fasting. The periods will be separated by a washout period of 7 days. The purpose of this study is to compare the bioavailability of Anplag® 90mg (Ticagrelor) Tablet with Brilinta® 90 mg (Ticagrelor) Tablet under fasting conditions in healthy Pakistani male subjects.

Detailed description: The subjects will be randomly assigned in period 1 to T or R sequence and will be administered the study drugs T (Anplag® 90 mg) or R (Brilinta® 90 mg) with 240 mL ambient temperature water following at least 10 hours fasting. Blood samples will be withdrawn at pre-determined time points for estimation of plasma drug concentration upto 48 hours post dose. the subjects will be crossed over in Period 2 separated by a washout period of 7 days and administered RT sequence in period 2. Similar procedure of blood sampling will be applied for estimation of plasma drug concentration upto 48 hours post dose.

Eligibility criteria: Inclusion Criteria:

* Healthy male aged 18 to 55 years inclusive.
* Subjects with a body mass index from 18.5 to 30.0 kg/m2.
* Subjects who are healthy as determined by routine physical examination, including vital sign monitoring (i.e., blood pressure, heart rate, and temperature), 12-lead ECG and laboratory analysis (i.e., hematology, blood biochemistry, Serology and urinalysis), or as determined by the investigator.
* Subjects should have negative urine test for drugs of abuse (Opiates and cannabinoids will be tested) and negative result for alcohol breath test at screening and prior to each check-in
* Tested negative for COVID-19 (through COVID-19 antibody testing).
* Subjects and their partners are willing to use reliable non-hormonal contraceptive methods (condoms, diaphragm, non-hormonal intra-uterine device (IUD), female or male sterilization or sexual abstinence) throughout the study and up to 30 days after the last administration of the study drug.
* All subjects should be free from any epidemic or contagious disease (e.g. Malaria, Dengue, COVID-19).
* Subjects are able to, understand and sign the Informed Consent Form for Medical Screening during their screening visit and Participation Informed Consent Form on study Check-In day
* Subject agreed not to consume food or beverages like tea, coffee, cola drinks, chocolates containing Xanthene derivatives (including caffeine, theobromines, etc.) and/or poppy seeds (Khashkhash) within 48-hours prior to drug administration until last blood draw in each study period.
* Subject agreed not to intake prescription medicine within 14 days or 5 half-lives (whichever is longer) prior to first dose of study medicine.
* Subject agreed not to intake non-prescription drugs (OTC such as aspirin, ibuprofen, naproxen, non-steroidal anti-inflammatory drugs (NSAIDs), or any other drug known to increase the tendency for bleeding within 14 days prior to first dose of study medicine.
* Subject agreed to discontinue vitamins, dietary and herbal supplements within 14 days prior to the first dose of study medication.
* Subject agreed not to consume grapefruit and/or its products within 14 days prior to the start of study.

Exclusion Criteria:

* Refused to sign Informed Consent Form.
* Inability to take oral medication.
* Tested positive for COVID-19 (through COVID-19 antibody testing).
* History of smoking (\> 5 cigarette/day), alcoholism, and positive test for drug of abuse.
* Heavy pan or gutka user as judged by teeth/mouth inspection.
* Subjects with clinically relevant evidence of cardiovascular, gastrointestinal/hepatic, renal, psychiatric, respiratory, urogenital, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, drug hypersensitivity, allergy, endocrine, major surgery or other relevant diseases as revealed by medical history, physical examination, and laboratory assessments which may interfere with the absorption, distribution, metabolism or elimination of drugs or constitute a risk factor when taking study medication.
* Donation or loss of more than 450 mL of blood within 3 months prior to the screening.
* History of intake of any prescribed medicine during a period of 30 days, prior to drug administration day of study.
* Subject is allergic to Ticagrelor and/or other antiplatelet medications/platelet aggregation inhibitors.
* Subject has received any investigational drug within four weeks prior to screening.
* Subjects whose heart rate is abnormally low (usually lower than 60 beats per minute) and subject already have in place a device that paces the heart (pacemaker).
* Subjects with a history of hemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding.
* A personal history of vascular abnormalities including aneurysms; a personal history of severe hemorrhage, non-traumatic bleeding, bleeding risks, hematemesis, melena, hemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage; or rectal bleeding within 1 year prior to screening; or history suggestive of peptic ulcer disease; or at the discretion of the investigator.
* Platelet count is less than 150 x 10\^9/L.
* Subject has had a blood test that showed more than the usual amount of uric acid.
* Subjects receiving oral anticoagulants often referred to as "blood thinners" which include warfarin.
* History of any significant illness in the last four weeks .
* Consumption of grapefruit and/or its products within 14 days prior to the start of study.
* Subjects who test positive for syphilis (VDRL) or who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs Ag) or are carriers of antibodies to hepatitis C virus (anti-HCV), human immunodeficiency virus (HIV-1 or HIV-2) or COVID-19.
* Individuals having undergone any major surgery (including dental work) within 3 months prior to the start of the study, unless deemed eligible, otherwise by the Principal Investigator or whomever he/she may designate.
* Subject has a history of any illness that, in the opinion of investigator might confound the result of the study or pose any risk in administrating Ticagrelor to the subject.
* Subjects with any condition, which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or elimination of drugs.

Primary outcomes:
measure: Cmax
timeFrame: 0-48 hours post dose
measure: Tmax
timeFrame: 0-48 hours post dose
measure: AUC
timeFrame: 0-48 hours post dose
Secondary outcomes:
measure: Blood pressure
timeFrame: 0-48 hours post dose
measure: Heart rate
timeFrame: 0-48 hours post dose
measure: Body temprature
timeFrame: 0-48 hours post dose
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Center for Bioequivalence Studies and clinical research
state: Sindh
Study officials:
affiliation: Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi, Pakistan
name: Prof. Dr. Muhammad R Shah, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi, Pakistan
name: Dr. Naghma Hashmi (Co-PI), PhD
role: PRINCIPAL_INVESTIGATOR
References: