CLINICAL TRIALS PROFILE FOR MEFLOQUINE HYDROCHLORIDE

505(b)(2) Clinical Trials for mefloquine hydrochloride

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.

All Clinical Trials for mefloquine hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00127998 ↗	Antimalarial Drug Resistance in Mali	Completed	Malaria Research and Training Center, Bamako, Mali	N/A	2005-07-01	Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to: 1. Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested. 2. Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria 3. Measure drug levels at 3 days and correlate with efficacy results. 4. Examine early clinical, parasitologic, and clinical predictors of late treatment failure. 5. Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.
NCT00127998 ↗	Antimalarial Drug Resistance in Mali	Completed	Centers for Disease Control and Prevention	N/A	2005-07-01	Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to: 1. Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested. 2. Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria 3. Measure drug levels at 3 days and correlate with efficacy results. 4. Examine early clinical, parasitologic, and clinical predictors of late treatment failure. 5. Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.
NCT00082576 ↗	Azithromycin Plus Chloroquine Versus Mefloquine for the Treatment of Uncomplicated Malaria in Africa	Completed	Pfizer	Phase 2/Phase 3	2004-06-01	The primary objective is to confirm the hypothesis that azithromycin plus chloroquine is non-inferior to mefloquine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum.
NCT00146718 ↗	Anti-Malarial Drug Resistance in Cameroon	Completed	University of Yaounde	Phase 2/Phase 3	2003-08-01	The project is a three-armed study designed to evaluate the efficacy of amodiaquine(AQ), sulphadoxine-pyrimethamine(SP) and(AQ+SP) in three sites in Cameroon that differ in their baseline characteristics for malaria. In addition, drug resistance will be determined by measurement of blood drug levels,and identification of molecular markers of resistance.

Clinical Trial Conditions for mefloquine hydrochloride

Condition Name

Condition Name for mefloquine hydrochloride
Intervention	Trials
Malaria	31
HIV Infections	5
Falciparum Malaria	4
Pregnancy	3

Condition MeSH

Condition MeSH for mefloquine hydrochloride
Intervention	Trials
Malaria	59
Malaria, Falciparum	21
HIV Infections	5
Malaria, Vivax	3

Clinical Trial Locations for mefloquine hydrochloride

Trials by Country

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−

Trials by Country for mefloquine hydrochloride
Location	Trials
Thailand	12
Kenya	8
Myanmar	8
Tanzania	7
United States	7

Trials by US State

+

−

Trials by US State for mefloquine hydrochloride
Location	Trials
Maryland	2
Texas	1
New York	1
Missouri	1
Massachusetts	1

Clinical Trial Progress for mefloquine hydrochloride

Clinical Trial Phase

Clinical Trial Phase for mefloquine hydrochloride
Clinical Trial Phase	Trials
Phase 4	14
Phase 3	24
Phase 2/Phase 3	10

Clinical Trial Status

Clinical Trial Status for mefloquine hydrochloride
Clinical Trial Phase	Trials
Completed	54
Terminated	9
Recruiting	6

Clinical Trial Sponsors for mefloquine hydrochloride

Sponsor Name

Sponsor Name for mefloquine hydrochloride
Sponsor	Trials
University of Oxford	13
Centers for Disease Control and Prevention	8
London School of Hygiene and Tropical Medicine	7

Sponsor Type

Sponsor Type for mefloquine hydrochloride
Sponsor	Trials
Other	176
U.S. Fed	19
Industry	16

Mefloquine Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction to Mefloquine Hydrochloride

Mefloquine hydrochloride, commonly known by its brand name Lariam, is an antimalarial drug used for the prevention and treatment of malaria caused by Plasmodium falciparum and Plasmodium vivax. Here, we will delve into the clinical trials, market analysis, and future projections for this drug.

Clinical Trials and Efficacy

Early Clinical Trials

One of the significant clinical trials for mefloquine was a phase II study conducted between January 1980 and April 1981. This double-blind, randomized trial involved 147 adult male patients with acute, uncomplicated falciparum malaria. The patients were administered single oral doses of 500, 750, or 1000 mg of mefloquine hydrochloride. The results showed satisfactory clinical and parasitological responses, with cure rates of 100%, 92.5%, and 95% for the 1000-, 750-, and 500-mg doses, respectively, over an observation period of 63 days[4].

Side Effects and Tolerability

The trial also highlighted the side effects associated with mefloquine, which were generally mild and transient, including nausea, vomiting, and diarrhea. However, one patient experienced an acute brain syndrome 21 days after receiving a 1000-mg dose, and sinus bradycardia was observed in 10 patients, although it was symptomless and required no treatment[4].

Special Populations

Mefloquine has been found to be well-tolerated in patients with acute renal failure, moderately severe malaria with jaundice, glucose-6-phosphate dehydrogenase deficiency, and thalassemia. However, it did not affect gametocytes of Plasmodium falciparum or tissue forms of P. vivax[4].

Market Analysis

Global Market Size and Growth

The global mefloquine market has been valued at several million dollars in recent years and is projected to grow at a significant Compound Annual Growth Rate (CAGR) through 2030. For instance, the global mefloquine market was valued at US$ million in 2023 and is expected to reach US$ million by 2030[2].

Regional Market Trends

The market for mefloquine is segmented by region, with notable growth expected in the USA, China, and Europe. In the USA, the market is estimated to increase from USD million in 2023 to USD million by 2030. Similarly, the China and Europe markets are also projected to see significant growth during the forecast period[2].

Key Players and Competitor Analysis

The global mefloquine hydrochloride market includes several key players, both major and minor. These companies are analyzed based on their company profiles, main business information, SWOT analysis, sales, revenue, price, and gross margin. The report also provides market share data for these competitors, helping to understand the competitive landscape[3].

Market Segmentation

Product Type Segment

The mefloquine hydrochloride market is segmented by product type, which includes different formulations and preparations of the drug. This segmentation helps in understanding the demand and supply dynamics of various product types[3].

End Use/Application Segment

The market is also segmented by end use or application, focusing on the status and outlook for key applications such as prophylaxis and treatment of malaria. Understanding these segments is crucial for identifying market opportunities and challenges[3].

Pharmacology and Pharmacokinetics

Absorption and Bioavailability

Mefloquine is readily absorbed from the gastrointestinal tract, with food significantly increasing its absorption and bioavailability by 40%. The bioavailability of tablets compared to the oral solution is over 85%. Peak plasma concentrations are achieved in 6 to 24 hours after a single dose[1].

Distribution and Protein Binding

The apparent volume of distribution in healthy adults is about 20 L/kg, with wide tissue distribution. Mefloquine can accumulate in erythrocytes infected with malaria parasites. The drug is highly bound to plasma proteins, with a binding rate of over 98%[1].

Metabolism and Elimination

The terminal elimination half-life of mefloquine ranges from 2 to 4 weeks, with a mean half-life of approximately 21 days. The systemic clearance ranges from 0.022 to 0.073 L/h/kg, with increased clearance during pregnancy[1].

Adverse Effects and Safety Concerns

Neuropsychiatric Effects

Mefloquine is associated with rare but potentially severe neuropsychiatric reactions, including acute brain syndrome, which has been observed in clinical trials. These effects are a significant concern and have led to black box warnings and precautions in the product information[1][5].

Other Adverse Effects

Common side effects include nausea, vomiting, diarrhea, and sinus bradycardia. Despite these side effects, mefloquine has been well-tolerated in various patient populations, including those with renal failure and glucose-6-phosphate dehydrogenase deficiency[4].

Market Projections and Outlook

Future Growth Drivers

The growth of the mefloquine market is driven by the increasing incidence of malaria, particularly in regions where chloroquine-resistant strains of Plasmodium falciparum are prevalent. The need for effective antimalarial drugs and the expanding healthcare infrastructure in developing countries are also key drivers[2].

Challenges and Limitations

Despite the growth potential, the mefloquine market faces challenges such as drug resistance in certain regions and the availability of alternative antimalarial drugs. The FDA's announcement of a temporary shortage of mefloquine hydrochloride also poses a challenge for its widespread use[5].

Key Takeaways

• Clinical Efficacy: Mefloquine hydrochloride has shown high efficacy in treating and preventing malaria caused by Plasmodium falciparum and Plasmodium vivax.
• Market Growth: The global mefloquine market is projected to grow significantly through 2030, driven by increasing demand in various regions.
• Pharmacology: Mefloquine has favorable pharmacokinetic properties, including high bioavailability and extensive tissue distribution.
• Safety Concerns: The drug is associated with rare but severe neuropsychiatric effects, necessitating careful patient monitoring.
• Market Segmentation: The market is segmented by product type, end use, and geography, providing insights into market dynamics.

FAQs

What is mefloquine hydrochloride used for?

Mefloquine hydrochloride is used for the treatment and prophylaxis of malaria caused by Plasmodium falciparum and Plasmodium vivax, including chloroquine-resistant forms of Plasmodium falciparum[1].

What are the common side effects of mefloquine?

Common side effects include nausea, vomiting, diarrhea, and sinus bradycardia. Rare but severe neuropsychiatric reactions can also occur[1][4].

How is mefloquine absorbed and metabolized?

Mefloquine is readily absorbed from the gastrointestinal tract, with peak plasma concentrations achieved in 6 to 24 hours. It has a high bioavailability and is extensively bound to plasma proteins. The drug has a terminal elimination half-life ranging from 2 to 4 weeks[1].

What are the market projections for mefloquine hydrochloride?

The global mefloquine market is projected to grow significantly through 2030, driven by increasing demand in regions such as the USA, China, and Europe[2].

Are there any safety concerns associated with mefloquine?

Yes, mefloquine is associated with rare but potentially severe neuropsychiatric reactions, which have led to black box warnings and precautions in the product information[1][5].

Sources

1. DrugBank: Mefloquine: Uses, Interactions, Mechanism of Action.
2. Hashnode: Global Mefloquine Market Research Report 2024(Status and Outlook).
3. 24ChemicalResearch: Mefloquine Hydrochloride Market.
4. PubMed: A phase II clinical trial of mefloquine in patients with chloroquine-resistant falciparum malaria.
5. CDC: Treatment of Uncomplicated Malaria.