Bioequivalence Study of Anplag® 90mg (Ticagrelor) Tablet & Brilinta® 90 mg (Ticagrelor) Tablet in Healthy Adult Male Pakistani Subjects Under Fasting Condition (BE)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Individuals
• Intervention / Treatment: Drug: Anplag (Ticagrelor 90 mg); Drug: Brilinta (Ticagrelor 90 mg)

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 Blood samples will be withdrawn at pre-determined time points for estimation of plasma drug concentration upto 48 hours post dose.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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75270
      • Center for Bioequivalence Studies and clinical research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Oral administration of Anplag® 90mg (Ticagrelor) whole Tablet, manufactured by PharmEvo Private Laboratories (Pak) Ltd., after at least 10 hours fast together with 240 mL of ambient temperature water at their scheduled dosing time-point.	Drug: Anplag (Ticagrelor 90 mg); Ticagrelor 90 mg Immediate Release tablet
Active Comparator: Reference Group; Oral administration of Brilinta® 90mg (Ticagrelor) Whole Tablet, manufactured by AstraZeneca Pharmaceuticals., after at least 10 hours fast together with 240 mL of ambient temperature water at their scheduled dosing time-point.	Drug: Brilinta (Ticagrelor 90 mg); Ticagrelor 90 mg Immediate Release tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Plasma Drug concentration	0-48 hours post dose
Tmax	Time required to reach maximum plasma Ticagrelor concentration	0-48 hours post dose
AUC	Area under the plsama drug concentration versus time curve	0-48 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	monitoring of blood pressure at specified time intervals	0-48 hours post dose
Heart rate	Monitoring of Heart rate at pre-specified time intervals	0-48 hours post dose
Body temprature	measurement of body temperature at pre-determined time intervals	0-48 hours post dose

Collaborators and Investigators

• Sponsor: University of Karachi
• Collaborators: PharmEvo Private Limited., Pakistan
• Investigators: Principal Investigator: Prof. Dr. Muhammad R Shah, PhD, Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi, Pakistan; Principal Investigator: Dr. Naghma Hashmi (Co-PI), PhD, Center for bio-equivalence studies and clinical research, ICCBS, University of Karachi, Pakistan

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Actual): October 26, 2020
• Study Completion (Actual): November 25, 2020

Study Registration Dates

• First Submitted: June 19, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Bioequivalence Study; Bioavailability comparison; Pakistani Population
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: CB-030-TIC-2019/Protocol/2.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data can be obtained upon proper request to principal investigator unless the volunteer's confidentiality is not compromised.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No