CLINICAL TRIALS PROFILE FOR COARTEM

505(b)(2) Clinical Trials for Coartem

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 Combination	NCT00694694 ↗	Azithromycin + Artesunate v Artemether-lumefantrine in Uncomplicated Malaria.	Completed	National Institute for Medical Research, Tanzania	Phase 3	2008-06-01	This trial sets out to determine whether the combination of azithromycin and artesunate (AZ+AS) is as good as the current standard treatment for uncomplicated malaria in Tanzania, artemether-lumefantrine (AL). There are two reasons this is important 1. there are only a limited range of drug combinations which work against malaria in this area of Tanzania 2. azithromycin has antimalarial properties, but is also a broad-spectrum antibiotic, so if the combination is an effective antimalarial it might have a place where there are no diagnostic facilities as syndromic treatment for fever. Artesunate and azithromycin have both been used alone or in combination with other drugs in children in Tanzania for many years, and are considered safe. There is trial evidence for the effectiveness of this combination in adults in Asia, as well as in-vitro (laboratory) evidence that it works against the malaria parasite. The trial randomizes children with non-severe malaria to the new combination AZ+AS or the standard care arm AL. The primary outcome is the parasitological failure rate by day 28- meaning do malaria parasites get cleared, and stay cleared for at least 28 days. Secondary outcomes include safety.
New Combination	NCT00694694 ↗	Azithromycin + Artesunate v Artemether-lumefantrine in Uncomplicated Malaria.	Completed	London School of Hygiene and Tropical Medicine	Phase 3	2008-06-01	This trial sets out to determine whether the combination of azithromycin and artesunate (AZ+AS) is as good as the current standard treatment for uncomplicated malaria in Tanzania, artemether-lumefantrine (AL). There are two reasons this is important 1. there are only a limited range of drug combinations which work against malaria in this area of Tanzania 2. azithromycin has antimalarial properties, but is also a broad-spectrum antibiotic, so if the combination is an effective antimalarial it might have a place where there are no diagnostic facilities as syndromic treatment for fever. Artesunate and azithromycin have both been used alone or in combination with other drugs in children in Tanzania for many years, and are considered safe. There is trial evidence for the effectiveness of this combination in adults in Asia, as well as in-vitro (laboratory) evidence that it works against the malaria parasite. The trial randomizes children with non-severe malaria to the new combination AZ+AS or the standard care arm AL. The primary outcome is the parasitological failure rate by day 28- meaning do malaria parasites get cleared, and stay cleared for at least 28 days. Secondary outcomes include safety.
New Combination	NCT01899820 ↗	Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya	Unknown status	Kenya Medical Research Institute	Phase 3	2013-04-01	Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs. This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice. Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including - Working towards the standardization of methodologies and common protocols as a way of comparing data across sites - Pulling together datasets and conduct a multi-centre analysis - Sharing and coordinating quality assurance mechanisms
New Combination	NCT01899820 ↗	Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya	Unknown status	World Bank	Phase 3	2013-04-01	Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs. This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice. Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including - Working towards the standardization of methodologies and common protocols as a way of comparing data across sites - Pulling together datasets and conduct a multi-centre analysis - Sharing and coordinating quality assurance mechanisms
New Combination	NCT01899820 ↗	Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya	Unknown status	Sabah Ahmed Omar	Phase 3	2013-04-01	Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs. This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice. Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including - Working towards the standardization of methodologies and common protocols as a way of comparing data across sites - Pulling together datasets and conduct a multi-centre analysis - Sharing and coordinating quality assurance mechanisms

All Clinical Trials for Coartem

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00118794 ↗	Lapdap and Coartemether for Uncomplicated Malaria	Completed	Medical Research Council	Phase 3	2004-09-01	Lapdap (chlorproguanil-dapsone) is an affordable and effective drug, but patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap; therefore there is a need to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment. The investigators will evaluate, in operational settings, the safety and effectiveness of Lapdap and coartemether (lumefantrine-artemether) for treatment of uncomplicated malaria in patients 6 months to 10 years of age.
NCT00118794 ↗	Lapdap and Coartemether for Uncomplicated Malaria	Completed	National Malaria Control Programme, The Gambia	Phase 3	2004-09-01	Lapdap (chlorproguanil-dapsone) is an affordable and effective drug, but patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap; therefore there is a need to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment. The investigators will evaluate, in operational settings, the safety and effectiveness of Lapdap and coartemether (lumefantrine-artemether) for treatment of uncomplicated malaria in patients 6 months to 10 years of age.
NCT00118794 ↗	Lapdap and Coartemether for Uncomplicated Malaria	Completed	London School of Hygiene and Tropical Medicine	Phase 3	2004-09-01	Lapdap (chlorproguanil-dapsone) is an affordable and effective drug, but patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap; therefore there is a need to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment. The investigators will evaluate, in operational settings, the safety and effectiveness of Lapdap and coartemether (lumefantrine-artemether) for treatment of uncomplicated malaria in patients 6 months to 10 years of age.
NCT00119145 ↗	Kintampo Trial of Combination Therapy for Malaria	Completed	Kintampo Health Research Centre, Ghana	Phase 4	2005-06-01	Case management is one of the key strategies for malaria control in most endemic countries. Plasmodium falciparum malaria is becoming resistant to commonly used and cheap antimalarial drugs such as chloroquine, amodiaquine, and sulfadoxine-pyrimethamine (SP). Thus the safety and efficacy of new anti-malarial drugs need to be tested in sites with well-characterised malariometric indices in order to make appropriate treatment policies. Artemisinin-based combination chemotherapies have been documented to consistently produce faster relief of clinical symptoms and parasite clearance in uncomplicated falciparum malaria than any other currently used antimalarial drugs. So far, artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AR-LM) are the only two registered fixed-dose artemisinin combination chemotherapies produced at industrial scale, with good manufacturing practices and already used in Africa. Several African countries, including Ghana, are therefore introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the case for such a change. Clearly, a direct comparison of both the safety and efficacy profiles of the two combinations under different epidemiological conditions is urgently needed to guide informed decisions on the most appropriate antimalarial first-line treatment regimen. This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination therapy, artemether-lumefantrine, and artesunate-lapdap in an open-labelled, randomised, non-inferiority drug trial. The study results will inform future decisions on first- and second-line treatments for uncomplicated P. falciparum malaria with respect to efficacy and safety in Ghana.
NCT00119145 ↗	Kintampo Trial of Combination Therapy for Malaria	Completed	Gates Malaria Partnership	Phase 4	2005-06-01	Case management is one of the key strategies for malaria control in most endemic countries. Plasmodium falciparum malaria is becoming resistant to commonly used and cheap antimalarial drugs such as chloroquine, amodiaquine, and sulfadoxine-pyrimethamine (SP). Thus the safety and efficacy of new anti-malarial drugs need to be tested in sites with well-characterised malariometric indices in order to make appropriate treatment policies. Artemisinin-based combination chemotherapies have been documented to consistently produce faster relief of clinical symptoms and parasite clearance in uncomplicated falciparum malaria than any other currently used antimalarial drugs. So far, artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AR-LM) are the only two registered fixed-dose artemisinin combination chemotherapies produced at industrial scale, with good manufacturing practices and already used in Africa. Several African countries, including Ghana, are therefore introducing either AS-AQ or AR-LM as first-line antimalarials or evaluating the case for such a change. Clearly, a direct comparison of both the safety and efficacy profiles of the two combinations under different epidemiological conditions is urgently needed to guide informed decisions on the most appropriate antimalarial first-line treatment regimen. This study aims to evaluate the efficacy and safety of artesunate-amodiaquine combination therapy, artemether-lumefantrine, and artesunate-lapdap in an open-labelled, randomised, non-inferiority drug trial. The study results will inform future decisions on first- and second-line treatments for uncomplicated P. falciparum malaria with respect to efficacy and safety in Ghana.

Clinical Trial Conditions for Coartem

Condition Name

Condition Name for Coartem
Intervention	Trials
Malaria	54
Malaria, Falciparum	8
Plasmodium Falciparum Malaria	6
Malaria,Falciparum	4

Condition MeSH

Condition MeSH for Coartem
Intervention	Trials
Malaria	85
Malaria, Falciparum	36
HIV Infections	4
Infections	2

Clinical Trial Locations for Coartem

Trials by Country

Trials by Country for Coartem
Location	Trials
Congo, The Democratic Republic of the	25
Mozambique	19
Kenya	14
Mali	13
Uganda	10

Trials by US State

Trials by US State for Coartem
Location	Trials
California	2

Clinical Trial Progress for Coartem

Clinical Trial Phase

Clinical Trial Phase for Coartem
Clinical Trial Phase	Trials
Phase 4	41
Phase 3	18
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for Coartem
Clinical Trial Phase	Trials
Completed	70
Not yet recruiting	6
Unknown status	5

Clinical Trial Sponsors for Coartem

Sponsor Name

Sponsor Name for Coartem
Sponsor	Trials
London School of Hygiene and Tropical Medicine	19
Centers for Disease Control and Prevention	13
Kenya Medical Research Institute	6

Sponsor Type

Sponsor Type for Coartem
Sponsor	Trials
Other	192
U.S. Fed	18
Industry	16

Coartem (Artemether/Lumefantrine): Clinical Trials, Market Analysis, and Projections

Introduction to Coartem

Coartem, a fixed-dose combination of artemether and lumefantrine, is a pivotal antimalarial drug developed by Novartis. It has been a cornerstone in the treatment of malaria since its FDA approval in 2009. Here, we will delve into the recent clinical trials, market analysis, and future projections for this essential medication.

Recent Clinical Trials: The CALINA Study

A significant milestone in the clinical trials of Coartem is the CALINA Phase II/III study, conducted by Novartis and Medicines for Malaria Venture (MMV). This study focused on developing a new formulation of Coartem specifically designed for infants weighing less than 5 kg (approximately 11 lbs) with acute uncomplicated malaria[1][4].

Key Findings of the CALINA Study

• The new formulation of Coartem demonstrated good efficacy and safety in treating malaria in infants under 5 kg.
• The study, conducted across several African countries, was the first evidence-based trial to evaluate a new antimalarial dose and regimen for this vulnerable population.
• The data from the CALINA study have been submitted for regulatory review, marking a crucial step towards providing an effective treatment for newborn babies with malaria[1][4].

Market Analysis of Coartem

Market Size and Forecast

The global Coartem market is projected to grow significantly over the forecast period from 2024 to 2031. Here are some key points from the market analysis:

• Market Segmentation: The market is segmented by application (Hospital Pharmacy, Retail Pharmacy, Online Pharmacy) and by product (Artemether, Lumefantrine), as well as by geographical regions (North America, Europe, Asia-Pacific, South America, and Middle-East and Africa)[5].
• Forecast Period: The forecast period spans from 2024 to 2031, with 2023 as the base year. The historical period for analysis is from 2021 to 2023[5].
• Market Value: The market size is measured in USD million, and the report predicts substantial growth in the value of the Coartem market during the forecast period[5].

Regional Analysis

The Coartem market is expected to be dominated by regions with high malaria prevalence, particularly in Africa and Asia-Pacific.

• Africa: Given the high burden of malaria in Africa, this region is expected to be a significant market for Coartem. The CALINA study, conducted in several African countries, underscores the importance of this market[1][4].
• Asia-Pacific: This region also experiences a considerable burden of malaria and is expected to contribute substantially to the market growth of Coartem[5].

Key Players

The market for Coartem is led by several key players, including:

• Novartis: As the developer and primary manufacturer of Coartem, Novartis plays a dominant role in the market.
• Other Players: Other companies such as Sanofi-aventis, Kpc Pharmaceuticals Inc, Guangxi Xiancaotang Pharmaceutical Co. Ltd, and Guilin Pharmaceutical Co. Ltd also participate in the market, though to a lesser extent[5].

Market Trends and Drivers

Increasing Malaria Prevalence

Despite global efforts to control malaria, the disease remains a significant public health challenge, particularly in tropical and subtropical regions. This ongoing need for effective antimalarial treatments drives the demand for Coartem[1].

Regulatory Support

The submission of the CALINA study data for regulatory review and potential approval will further boost the market for Coartem, especially for the new formulation designed for infants under 5 kg[1][4].

Technological Advancements

Continuous research and development in antimalarial therapies, including the optimization of existing treatments like Coartem, contribute to market growth. The new formulation of Coartem for infants is a prime example of such advancements[1].

Challenges and Restraints

Drug Interactions and Side Effects

Coartem, like other antimalarial drugs, can have interactions with other medications and may cause side effects. For instance, coadministration with CYP3A4 inhibitors or inducers can affect the efficacy and safety of Coartem[3].

Access and Affordability

In many regions where malaria is prevalent, access to and affordability of Coartem can be significant challenges. Efforts by Novartis and MMV to make the treatment available as soon as possible to vulnerable populations are crucial in addressing these issues[1].

Future Projections

Market Growth

The Coartem market is expected to grow at a good pace, driven by increasing demand, regulatory approvals, and ongoing research to improve treatment options. The market size is projected to increase substantially over the forecast period from 2024 to 2031[5].

Expanding Treatment Options

The success of the CALINA study and the potential approval of the new Coartem formulation for infants under 5 kg will expand the treatment options for malaria, particularly for vulnerable newborn babies. This expansion is expected to further drive market growth[1][4].

Key Takeaways

• Clinical Trials: The CALINA Phase II/III study has shown promising results for a new Coartem formulation designed for infants under 5 kg with malaria.
• Market Analysis: The global Coartem market is projected to grow significantly, driven by increasing demand and regulatory approvals.
• Market Segmentation: The market is segmented by application, product, and geographical regions, with Africa and Asia-Pacific expected to be key markets.
• Challenges: Despite the positive outlook, challenges such as drug interactions, side effects, and access/affordability issues need to be addressed.

FAQs

What is the significance of the CALINA study for Coartem?

The CALINA study is the first evidence-based trial to evaluate a new antimalarial dose and regimen for infants weighing under 5 kg with acute uncomplicated malaria, demonstrating good efficacy and safety for this vulnerable population[1][4].

How does the new Coartem formulation differ from the existing one?

The new formulation uses a new ratio and dose of artemether-lumefantrine to account for metabolic differences in babies under 5 kg, making it suitable for treating malaria in infants[1].

What are the key drivers of the Coartem market?

The key drivers include increasing malaria prevalence, regulatory support, and technological advancements in antimalarial therapies[1][5].

Which regions are expected to dominate the Coartem market?

Africa and Asia-Pacific are expected to dominate the market due to the high burden of malaria in these regions[5].

What are the potential challenges for the Coartem market?

Challenges include drug interactions, side effects, and issues related to access and affordability in regions where malaria is prevalent[3].

Sources

1. Novartis and Medicines for Malaria Venture announce positive efficacy and safety data from novel treatment for babies with malaria. Novartis, April 24, 2024.
2. Global Coartem Artemether Lumefantrine Market Report 2024. Cognitivemarketresearch.com.
3. COARTEM® (artemether and lumefantrine) Tablets. Novartis.
4. Novartis, Medicines for Malaria Venture Release Positive Results from Phase II/III Trial of Coartem for Infants with Malaria. Pharmexec.com, April 25, 2024.
5. Coartem (Artemether/Lumefantrine) Market Size, Share and Forecast. Marketresearchintellect.com, January 2025.