CLINICAL TRIALS PROFILE FOR TICAGRELOR

505(b)(2) Clinical Trials for ticagrelor

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Dosage	NCT02435563 ↗	Dose Adaptation to Offset the Interaction Between Ticagrelor and Ritonavir by Population-based PK Modeling	Completed	University Hospital, Geneva	Phase 2	2014-08-01	Ticagrelor is a new generation antiplatelet agent with higher efficacy as compared to clopidogrel and prasugrel in treatment of patients with moderate and high ischemic risks. Ticagrelor is active as such and its hepatic metabolism by CYP3A generates also an active metabolite. Because of the remarkable progress in HIV therapies the number of older age patients is on the rise, requiring adequate cardiovascular treatment. Since frontline HIV therapies include ritonavir, a strong inhibitor of CYP3A enzyme, ticagrelor is contraindicated in these patients because of the expected interaction and bleeding risk. A lower efficacy of clopidogrel and prasugrel, which are both pro-drugs, in the presence of ritonavir has been already demonstrated. Therefore, administration of a lower dose of ticagrelor may be a good alternative in HIV patients in order to lessen the impact of this pharmacokinetic interaction. The aim of this study is to adjust the dose of ticagrelor in case of co-treatment with ritonavir to achieve the same pharmacokinetic profile as administered alone using a physiologically-based pharmacokinetic (PBPK) model. As the first step, a pharmacokinetic (PK) model for ticagrelor and its active metabolite will be created based on available in vitro and in vivo parameters in healthy volunteers. An open-label, 2 sessions cross over study will be conducted with 20 healthy male volunteers at Clinical Research Center (CRC) of Geneva University Hospitals (HUG). During the first session of the clinical trial, a single dose 180 mg ticagrelor will be administered to the volunteers and obtained pharmacokinetic data will be fitted into the model for optimization. Thereafter a simulated trial by the Simcyp® simulator in presence of a single dose 100 mg ritonavir will allow evaluating the impact of CYP3A inhibition on the concentration-time profile of ticagrelor and its active metabolite. The necessary dose of ticagrelor to minimize the magnitude of this interaction will be calculated. This new dose will be co-administered with ritonavir in the same volunteers during the second session of the clinical trial. The purpose is to obtain the same PK profile with single dose of 180 mg ticagrelor administered alone and with an adapted dose of ticagrelor co-administered with a single dose 100 mg ritonavir. Moreover, the pharmacodynamic effect of ticagrelor will be measured in both sessions of the clinical trial using two specific platelet function tests: the VAsodilator-Stimulated Phosphoprotein assay (VASP) and VerifyNow® P2Y12. With the same PK profile, the same pharmacodynamic activity is expected. The modulation of activity of CYP3A and P-gp by ritonavir will be also monitored using micro dose midazolam and fexofenadine as probe substrates. The purpose of this study is to use the Simcyp® Simulator mechanistic PBPK modeling to broaden the application field of ticagrelor, especially in HIV patients. Since PK models are often created after clinical observations, the prospective aspect of this study is of particular value as the model will be first created and then applied to an unknown clinical scenario.

All Clinical Trials for ticagrelor

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01226602 ↗	Study to Assess the Effect of Ticagrelor on Coronary Blood Flow in Healthy Male Subjects.	Completed	AstraZeneca	Phase 1	2010-12-01	The purpose of this study is to determine if Ticagrelor increases the Adenosin induced coronary blood flow velocity.
NCT01225562 ↗	Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin	Completed	AstraZeneca	Phase 3	2010-10-01	This study is being carried out to see if a new drug called ticagrelor given twice daily in addition to the ASA therapy decreases the frequency of cardiovascular events (e.g., death from heart disease, heart attack, or stroke).
NCT01118325 ↗	An Asian Study to Assess the Properties and Profile of Ticagrelor in Patients With Stable Coronary Artery Disease	Completed	AstraZeneca	Phase 2	2010-04-01	The purpose of the study is to determine the drug characteristics of Ticagrelor, and to determine if 4 weeks treatment will reduce the blood clotting.
NCT01087723 ↗	European Ambulance Acute Coronary Syndrome (ACS) Angiography Trial	Completed	The Medicines Company	Phase 3	2010-03-01	To show that the early administration of bivalirudin improves 30 day outcomes when compared to the current standard of care in participants with ST segment elevation acute coronary syndrome (STE-ACS), intended for a primary percutaneous coronary intervention (PCI) management strategy, presenting either via ambulance or to centers where PCI is not performed.
NCT00642811 ↗	A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders	Completed	AstraZeneca	Phase 2	2008-05-01	The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated the effect of Ticagrelor on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel.
NCT00528411 ↗	A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin	Completed	AstraZeneca	Phase 2	2007-10-01	The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated how long it takes for Ticagrelor to begin working and how long it takes for it to stop working after the last dose of drug. Ticagrelor will be compared to clopidogrel, an established anti-platelet treatment for preventing blood clots, and placebo plus Aspirin.
NCT00391872 ↗	A Comparison of Ticagrelor (AZD6140) and Clopidogrel in Patients With Acute Coronary Syndrome	Completed	AstraZeneca	Phase 3	2006-10-01	Ticagrelor is a new, reversible binding, anti-platelet medication. Anti-platelet medications work to prevent the formation of blood clots. Ticagrelor is being developed as a treatment for patients with acute coronary syndrome (ACS). ACS is a term that is used to describe both heart attacks in progress or the imminent threat of a heart attack. ACS is usually caused by the formation of a blood clot in an artery that partially or totally blocks the blood supply to a portion of the heart muscle. Ticagrelor will be compared with clopidogrel to determine which drug, when either is used in conjunction with aspirin, is better at reducing deaths from vascular causes, future heart attacks and/or strokes in patients with ACS.

Clinical Trial Conditions for ticagrelor

Condition Name

Condition Name for ticagrelor
Intervention	Trials
Coronary Artery Disease	94
Acute Coronary Syndrome	81
Myocardial Infarction	28
Acute Myocardial Infarction	14

Condition MeSH

Condition MeSH for ticagrelor
Intervention	Trials
Coronary Artery Disease	117
Acute Coronary Syndrome	112
Myocardial Ischemia	97
Coronary Disease	96

Clinical Trial Locations for ticagrelor

Trials by Country

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−

Trials by Country for ticagrelor
Location	Trials
United States	662
China	176
Canada	100
Japan	62
Italy	61

Trials by US State

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−

Trials by US State for ticagrelor
Location	Trials
Florida	47
Texas	28
New York	26
California	25
Pennsylvania	23

Clinical Trial Progress for ticagrelor

Clinical Trial Phase

Clinical Trial Phase for ticagrelor
Clinical Trial Phase	Trials
Phase 4	222
Phase 3	73
Phase 2/Phase 3	12

Clinical Trial Status

Clinical Trial Status for ticagrelor
Clinical Trial Phase	Trials
Completed	225
Recruiting	60
Unknown status	59

Clinical Trial Sponsors for ticagrelor

Sponsor Name

Sponsor Name for ticagrelor
Sponsor	Trials
AstraZeneca	86
University of Florida	21
University of Patras	12

Sponsor Type

Sponsor Type for ticagrelor
Sponsor	Trials
Other	536
Industry	142
NIH	5

Ticagrelor: Clinical Trials, Market Analysis, and Projections

Introduction to Ticagrelor

Ticagrelor, a potent antiplatelet drug, is widely used in the management of acute coronary syndrome (ACS) and to prevent thrombotic events in patients with a history of heart attack or severe chest pain. Here, we will delve into the recent clinical trials, market analysis, and future projections for ticagrelor.

Clinical Trials Update

T-PASS Trial

The T-PASS trial is a significant recent study that evaluated the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) with bioresorbable polymer sirolimus-eluting stents for ACS. The trial demonstrated that ticagrelor monotherapy after less than one month of dual antiplatelet therapy (DAPT) was both noninferior and superior to a conventional 12-month DAPT regimen. The primary outcome, net adverse cardiovascular events, was significantly lower in the monotherapy group, primarily due to a reduction in bleeding events[1].

TICO Trial

The TICO trial focused on patients treated with new-generation sirolimus-eluting stents for ACS and compared ticagrelor monotherapy after 3 months of DAPT to 12 months of DAPT. The results showed that ticagrelor monotherapy reduced the risk of bleeding without increasing the risk of ischemic complications. This was particularly evident in patients with small vessel disease, where ticagrelor monotherapy significantly reduced BARC type 3 or 5 bleeding[3].

GLOBAL LEADERS Trial

The GLOBAL LEADERS trial compared the efficacy and safety of ticagrelor monotherapy following 1 month of DAPT to aspirin monotherapy following 12 months of DAPT. The landmark analysis revealed that ticagrelor monotherapy was superior to aspirin monotherapy in reducing ischemic risk among patients who were free from ischemic and bleeding events during the first year after PCI[4].

Market Analysis

Current Market Size and Growth

The global ticagrelor market has been growing steadily. As of 2022, the market size was valued at USD 1,421.74 million. It is projected to grow at a compound annual growth rate (CAGR) of 6.83% from 2024 to 2031[2].

Historical and Forecasted Data

Historically, the ticagrelor market was valued at US$ 1,145.0 million in 2017 and witnessed a CAGR of 12.3% during the period from 2018 to 2026. The market growth is driven by a high patient pool suffering from heart diseases, increasing generic drug development, and improving market access scenarios[5].

Market Segmentation

The ticagrelor market is segmented based on dosage, application, end user, and route of administration. The analysis provides insights into the key industry segments and their global, regional, and country-level growth. The market is expected to be influenced by factors such as the rising global burden of heart diseases and significant approvals from regulatory bodies like the U.S. Food and Drug Administration (FDA)[2][5].

Market Projections

Growth Drivers

The ticagrelor market is expected to grow significantly due to several factors:

• Increasing Burden of Heart Diseases: Cardiovascular diseases are a leading cause of morbidity and mortality globally, driving the demand for effective antiplatelet therapies like ticagrelor[5].
• Regulatory Approvals: Recent approvals for ticagrelor, such as the FDA approval for ticagrelor tablets in 2018, will continue to support market growth[5].
• Generic Drug Development: The increasing availability of generic versions of ticagrelor is expected to expand market access and drive growth[5].

Challenges

Despite the positive outlook, the market may face challenges such as:

• Product Failures: Instances of product failures, like the failure of Brilinta in peripheral artery disease (PAD), can impact market growth[5].
• Competition: The antiplatelet market is competitive, with other drugs like clopidogrel and prasugrel, which could affect ticagrelor's market share.

Clinical Implications and Future Directions

Reduction in Bleeding Complications

Clinical trials have consistently shown that ticagrelor monotherapy after a short period of DAPT reduces bleeding complications without increasing the risk of ischemic events. This is particularly beneficial for patients with small vessel disease and those at high risk of bleeding[1][3].

Patient Subgroups

Further studies are needed to assess the efficacy and safety of ticagrelor monotherapy in specific subgroups that exhibit a high risk of ischemic or bleeding events. This will help in tailoring antiplatelet therapy to individual patient needs[3].

Key Takeaways

• Clinical Trials: Recent trials like T-PASS, TICO, and GLOBAL LEADERS have demonstrated the efficacy and safety of ticagrelor monotherapy after short-term DAPT.
• Market Growth: The global ticagrelor market is projected to grow at a CAGR of 6.83% from 2024 to 2031.
• Growth Drivers: Increasing burden of heart diseases, regulatory approvals, and generic drug development are key drivers of market growth.
• Challenges: Product failures and competition from other antiplatelet drugs are potential challenges.

FAQs

Q: What is the primary outcome of the T-PASS trial?

A: The primary outcome of the T-PASS trial was the net adverse cardiovascular events, which showed that ticagrelor monotherapy after less than one month of DAPT was both noninferior and superior to 12 months of DAPT[1].

Q: How does ticagrelor monotherapy compare to aspirin monotherapy in the GLOBAL LEADERS trial?

A: The GLOBAL LEADERS trial showed that ticagrelor monotherapy was superior to aspirin monotherapy in reducing ischemic risk among patients who were free from ischemic and bleeding events during the first year after PCI[4].

Q: What is the projected CAGR for the global ticagrelor market from 2024 to 2031?

A: The global ticagrelor market is projected to grow at a CAGR of 6.83% from 2024 to 2031[2].

Q: What are the key factors driving the growth of the ticagrelor market?

A: The key factors driving the growth of the ticagrelor market include the increasing burden of heart diseases, regulatory approvals, and generic drug development[5].

Q: What challenges might the ticagrelor market face?

A: The ticagrelor market might face challenges such as product failures and competition from other antiplatelet drugs[5].

Sources

1. Ticagrelor Monotherapy in Patients Treated With New-Generation Drug-Eluting Stents for Acute Coronary Syndrome - T-PASS. American College of Cardiology.
2. Ticagrelor Market Report 2024 (Global Edition). Cognitive Market Research.
3. Clinical implication of ticagrelor monotherapy in patients with small vessel disease. Frontiers in Cardiovascular Medicine.
4. Ticagrelor monotherapy versus aspirin monotherapy at 12 months after percutaneous coronary intervention: a landmark analysis of the GLOBAL LEADERS trial. EuroIntervention.
5. Ticagrelor Market Size and Trends. Coherent Market Insights.