CLINICAL TRIALS PROFILE FOR AMLODIPINE BESYLATE; CELECOXIB

All Clinical Trials for amlodipine besylate; celecoxib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02172040 ↗	Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy	Completed	Kitov Pharmaceuticals, Ltd.	Phase 3	2014-06-26	The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety of amlodipine besylate in subjects with newly diagnosed hypertension requiring antihypertensive therapy. This study was conducted to support a future marketing application for KIT-302. Kitov Pharma Ltd. (Kitov) is developing KIT-302, an oral fixed combination drug product (FCDP) consisting of the calcium channel blocker amlodipine besylate and the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, as a "convenience reformulation" FCDP to facilitate and improve patient compliance with the once a day (qd) administration of its individual components, amlodipine and celecoxib. The formulation of KIT-302 consists of amlodipine besylate and celecoxib co-formulated in a single immediate release tablet. However, for this study, two separate capsules were utilized: one containing a commercial celecoxib capsule (Celebrex®) or matched placebo capsule and one containing a commercial amlodipine besylate tablet (Norvasc®) or matched placebo tablet. The study hypothesis was that treatment with the amlodipine besylate containing capsule plus the celecoxib containing capsule would reduce blood pressure (BP) in subjects with hypertension with an efficacy that is not substantially inferior to the effect of amlodipine besylate alone (i.e., the amlodipine containing capsule plus the matched placebo for the celecoxib capsule). The United States (US) Food and Drug Administration (FDA) recently approved KIT-302, under the brand name Consensi® (amlodipine and celecoxib) tablets [New Drug Application (NDA) 210045] for the following indication: "patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions."
NCT02979197 ↗	Evaluation of Celecoxib Effects on Amlodipine in Subjects With Existing Hypertension Requiring Antihypertensives	Completed	Kitov Pharma Ltd	Phase 3	2016-11-03	The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety of amlodipine besylate on renal and vascular function in subjects with existing hypertension requiring antihypertensive therapy. Kitov Pharma Ltd. (Kitov) is developing KIT-302, an oral fixed combination drug product (FCDP) consisting of the calcium channel blocker amlodipine besylate and the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, as a "convenience reformulation" FCDP to facilitate and improve patient compliance with the once a day (qd) administration of its individual components, amlodipine and celecoxib. The formulation of KIT-302 consists of amlodipine besylate and celecoxib co-formulated in a single immediate release tablet. However, for this study (KIT-302-03-02), commercial celecoxib capsules (Celebrex®) and commercial amlodipine besylate tablets (Norvasc®) were separately over-encapsulated (OE) and matched placebos were used to allow for blinding. Kitov completed a phase 3 pivotal trial in subjects with newly diagnosed hypertension (KIT-302-03-01) demonstrating that the amlodipine + celecoxib combination was statistically non-inferior to amlodipine monotherapy with regard to reduction of blood pressure. Further, trends towards superior blood pressure lowering effects and improved renal function were observed for the combination. This study (KIT-302-03-02) was conducted to quantify the beneficial renovascular effects noted in the prior study in subjects with existing hypertension requiring antihypertensive therapy. On May 31, 2018, the United States (US) Food and Drug Administration (FDA) approved KIT-302, under the brand name Consensi® (amlodipine and celecoxib) tablets [New Drug Application (NDA) 210045] for the following indication: "patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions."
NCT02979197 ↗	Evaluation of Celecoxib Effects on Amlodipine in Subjects With Existing Hypertension Requiring Antihypertensives	Completed	Kitov Pharmaceuticals, Ltd.	Phase 3	2016-11-03	The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety of amlodipine besylate on renal and vascular function in subjects with existing hypertension requiring antihypertensive therapy. Kitov Pharma Ltd. (Kitov) is developing KIT-302, an oral fixed combination drug product (FCDP) consisting of the calcium channel blocker amlodipine besylate and the nonsteroidal anti-inflammatory drug (NSAID) celecoxib, as a "convenience reformulation" FCDP to facilitate and improve patient compliance with the once a day (qd) administration of its individual components, amlodipine and celecoxib. The formulation of KIT-302 consists of amlodipine besylate and celecoxib co-formulated in a single immediate release tablet. However, for this study (KIT-302-03-02), commercial celecoxib capsules (Celebrex®) and commercial amlodipine besylate tablets (Norvasc®) were separately over-encapsulated (OE) and matched placebos were used to allow for blinding. Kitov completed a phase 3 pivotal trial in subjects with newly diagnosed hypertension (KIT-302-03-01) demonstrating that the amlodipine + celecoxib combination was statistically non-inferior to amlodipine monotherapy with regard to reduction of blood pressure. Further, trends towards superior blood pressure lowering effects and improved renal function were observed for the combination. This study (KIT-302-03-02) was conducted to quantify the beneficial renovascular effects noted in the prior study in subjects with existing hypertension requiring antihypertensive therapy. On May 31, 2018, the United States (US) Food and Drug Administration (FDA) approved KIT-302, under the brand name Consensi® (amlodipine and celecoxib) tablets [New Drug Application (NDA) 210045] for the following indication: "patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions."
NCT03299452 ↗	Clinical Studies by Using Alphacait to Screen Drugs for Advanced Solid Tumor	Unknown status	Alphacait, LLC	Phase 2	2017-01-01	This is a single-center, open-label, single-arm, non-randomized study designed to evaluate PFS, safety, overall survival (OS), objective response rate (OPR), disease control rate (DCR) and biomarkers of cancer therapy based on Alphacait screening system in subjects with advanced malignant tumor.
NCT03299452 ↗	Clinical Studies by Using Alphacait to Screen Drugs for Advanced Solid Tumor	Unknown status	Haining Health-Coming Biotech Co., Ltd.	Phase 2	2017-01-01	This is a single-center, open-label, single-arm, non-randomized study designed to evaluate PFS, safety, overall survival (OS), objective response rate (OPR), disease control rate (DCR) and biomarkers of cancer therapy based on Alphacait screening system in subjects with advanced malignant tumor.

Clinical Trial Conditions for amlodipine besylate; celecoxib

Condition Name

Condition Name for amlodipine besylate; celecoxib
Intervention	Trials
Hypertension	2
Metastatic Cancer	1

Condition MeSH

Condition MeSH for amlodipine besylate; celecoxib
Intervention	Trials
Hypertension	2
Neoplasm Metastasis	1

Clinical Trial Locations for amlodipine besylate; celecoxib

Trials by Country

Trials by Country for amlodipine besylate; celecoxib
Location	Trials
United Kingdom	8
China	1

Clinical Trial Progress for amlodipine besylate; celecoxib

Clinical Trial Phase

Clinical Trial Phase for amlodipine besylate; celecoxib
Clinical Trial Phase	Trials
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for amlodipine besylate; celecoxib
Clinical Trial Phase	Trials
Completed	2
Unknown status	1

Clinical Trial Sponsors for amlodipine besylate; celecoxib

Sponsor Name

Sponsor Name for amlodipine besylate; celecoxib
Sponsor	Trials
Kitov Pharmaceuticals, Ltd.	2
Kitov Pharma Ltd	1
Alphacait, LLC	1

Sponsor Type

Sponsor Type for amlodipine besylate; celecoxib
Sponsor	Trials
Other	3
Industry	2

Amlodipine besylate; celecoxib Market Analysis and Financial Projection

Amlodipine Besylate and Celecoxib: Clinical Trials, Market Analysis, and Projections

Introduction

Amlodipine besylate and celecoxib, combined in the fixed-dose formulation known as Consensi®, have been approved by the FDA for the treatment of comorbid hypertension and osteoarthritis. Here, we delve into the latest updates on clinical trials, market analysis, and future projections for this combination drug.

Clinical Trials Update

Phase 3 Clinical Trials

Although no clinical trials have been published in peer-reviewed literature, results from two phase 3 clinical trials reported to ClinicalTrials.gov indicate that the amlodipine-celecoxib combination has similar short-term efficacy to amlodipine alone in reducing blood pressure. Additionally, the combination shows a comparable adverse event profile to the individual components administered separately[1].

Efficacy and Safety

The trials suggest that the combination does not offer significant advantages in terms of efficacy over the individual drugs but does reduce the pill burden for patients. However, the lack of long-term data on safety and efficacy remains a concern. The PRECISION trial, which compared celecoxib to non-selective NSAIDs, found that celecoxib was non-inferior in terms of cardiovascular thrombotic risk, but it also highlighted potential liver enzyme elevations and other adverse effects associated with celecoxib[4].

Market Analysis

Current Market Size

The amlodipine besylate market was valued at USD 1867.0 million in 2023, while the broader amlodipine market stood at US$ 413.0 million. These markets are expected to grow, driven by the increasing prevalence of hypertension and the need for antihypertensive medications[3][5].

Growth Projections

The amlodipine besylate market is projected to grow at a CAGR of 3.98% from 2024 to 2031, reaching a significant market size by the end of the forecast period. The amlodipine market, in general, is expected to advance at a CAGR of 4.4% from 2024 to 2034, reaching US$ 670.3 million by 2034[3][5].

Regional Dominance

North America, particularly the U.S., holds the largest share of the amlodipine besylate market due to a sizable population suffering from hypertension. This region is expected to continue leading the market during the forecast period[5].

Cost and Accessibility

Cost Considerations

One of the significant challenges for the amlodipine-celecoxib combination is its high cost relative to the generic components. This cost disparity, combined with limited flexibility for dose adjustment, makes the combination less appealing to some healthcare providers and patients[1].

Analytical Methods for Quantification

RP-HPLC Method

A recent study developed and validated a simple, precise, and accurate RP-HPLC method with UV detection for the quantification of amlodipine besylate and celecoxib in their fixed-dose formulation. This method uses a Thermosil C18 analytical column and a mobile phase composed of methanol and 0.1% orthophosphoric acid. The method was successfully applied to analyze commercial dosage forms, ensuring high recovery rates and robustness[2].

Expert Opinion and Clinical Use

Role in Management

Despite the reduction in pill burden, the role of amlodipine-celecoxib in managing patients with hypertension and osteoarthritis remains questionable. Experts highlight the need for long-term safety and efficacy data to fully endorse this combination as a standard treatment option[1].

Adverse Effects and Monitoring

Healthcare providers must be vigilant about potential adverse effects, particularly liver enzyme elevations and cardiovascular risks associated with celecoxib. Patients should be informed of the warning signs and symptoms of hepatotoxicity and other systemic manifestations, and the drug should be discontinued immediately if such signs appear[4].

Regulatory Considerations

FDA Approval

Consensi® is indicated for adult patients for whom treatment with both amlodipine for hypertension and celecoxib for osteoarthritis is appropriate. The FDA approval is based on the clinical trials and safety data available, but ongoing monitoring is necessary to address long-term safety concerns[4].

Future Projections and Challenges

Market Growth Drivers

The growing prevalence of hypertension and osteoarthritis, coupled with the need for convenient, single-pill solutions, will drive the market for amlodipine besylate and celecoxib combinations. However, the high cost and limited flexibility in dosing will need to be addressed to make this option more viable.

Research and Development

Future research should focus on long-term safety and efficacy studies to solidify the position of amlodipine-celecoxib combinations in clinical practice. Additionally, efforts to reduce the cost and improve dosing flexibility could enhance the market appeal of this combination.

Key Takeaways

• Clinical Trials: The amlodipine-celecoxib combination shows similar short-term efficacy to amlodipine alone but lacks long-term safety and efficacy data.
• Market Analysis: The market for amlodipine besylate and celecoxib is growing, driven by the prevalence of hypertension and osteoarthritis, but is hindered by high costs.
• Analytical Methods: RP-HPLC methods have been developed and validated for the quantification of amlodipine besylate and celecoxib in fixed-dose formulations.
• Clinical Use: The combination reduces pill burden but faces challenges due to cost and limited dosing flexibility.
• Regulatory Considerations: FDA approval is based on available data, but ongoing monitoring is necessary.

FAQs

Q: What is the current market size of the amlodipine besylate market?

The amlodipine besylate market was valued at USD 1867.0 million in 2023[3].

Q: What are the projected growth rates for the amlodipine besylate and amlodipine markets?

The amlodipine besylate market is expected to grow at a CAGR of 3.98% from 2024 to 2031, while the broader amlodipine market is projected to advance at a CAGR of 4.4% from 2024 to 2034[3][5].

Q: What are the main challenges for the amlodipine-celecoxib combination?

The main challenges include high cost relative to generic components, limited flexibility for dose adjustment, and the lack of long-term safety and efficacy data[1].

Q: How is the amlodipine-celecoxib combination quantified in commercial formulations?

The combination is quantified using a validated RP-HPLC method with UV detection, ensuring high recovery rates and robustness[2].

Q: What are the potential adverse effects of the amlodipine-celecoxib combination?

Potential adverse effects include liver enzyme elevations, cardiovascular risks, and other systemic manifestations associated with celecoxib[4].

Sources

1. PubMed: Fixed-dose combination amlodipine-celecoxib for treatment of comorbid hypertension and osteoarthritis.
2. IJBPAS: Estimation of amlodipine besylate and celecoxib in combined dosage form by RP-HPLC.
3. Kings Research: Amlodipine Besylate Market Size & Share Forecast [2031].
4. FDA: CONSENSI label.
5. Transparency Market Research: Amlodipine Market Size, Share, Growth, Current Analysis, 2034.