CLINICAL TRIALS PROFILE FOR ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

All Clinical Trials for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00084227 ↗	Azithromycin Plus Chloroquine Versus Atovaquone-Proguanil For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In South America	Completed	Pfizer	Phase 2/Phase 3	2004-07-01	The primary objective is to confirm the hypothesis that azithromycin plus chloroquine is non-inferior to atovaquone-proguanil for the treatment of symptomatic, uncomplicated malaria due to P. falciparum.
NCT00149383 ↗	Safety and Efficacy Study of Adjunctive Rosiglitazone in the Treatment of Uncomplicated Falciparum Malaria	Completed	McLaughlin-Rotman Center for Global Health, University of Toronto	Phase 1/Phase 2	2004-12-01	The purpose of this study is to examine the safety, tolerability, and efficacy of adjunctive rosiglitazone in the treatment of uncomplicated P.falciparum malaria.
NCT00149383 ↗	Safety and Efficacy Study of Adjunctive Rosiglitazone in the Treatment of Uncomplicated Falciparum Malaria	Completed	Mahidol University	Phase 1/Phase 2	2004-12-01	The purpose of this study is to examine the safety, tolerability, and efficacy of adjunctive rosiglitazone in the treatment of uncomplicated P.falciparum malaria.
NCT00379821 ↗	Chloroquine Alone or in Combination for Malaria in Children in Malawi	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	2007-02-01	Malaria is a sickness caused by a germ that can get into a person's body when a mosquito bites them. It can cause fever, headache, body aches and weakness. It can even cause death, especially in children. When malaria is treated with the appropriate medicine(s), it can be cured completely. The purpose of this study is to find out if it is better to use chloroquine alone or in combination with another drug to most effectively treat malaria. About 640 children with malaria, aged 6 months to 5 years of age, from the Blantyre Malaria Project Research Clinic at the Ndirande Health Center in Malawi will be in the study. They will be treated with either chloroquine alone or a combination of chloroquine plus another medication (azithromycin or artesunate or atovaquone-proguanil) every time they get malaria for a year. Blood samples will be collected and tested at least every 4 weeks. Participants will be involved in the study for 1 year.
NCT00386750 ↗	Safety of Artemether - Lumefantrine, and Other Malaria Drugs and Their Effect on the Auditory Function	Terminated	Novartis Pharmaceuticals	Phase 4	2005-06-01	THIS STUDY IS NOT ENROLLING PATIENTS IN THE USA. To evaluate the effects of artemether/ lumefantrine on the auditory function.
NCT00421473 ↗	Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients	Completed	Radboud University	Phase 4	2007-03-01	Malarone® (atovaquone/proguanil) is frequently used in malaria prophylaxis. Unfortunately, there are indications that certain anti-HIV agents may decrease atovaquone plasma levels by induction of atovaquone metabolism. For travelling HIV patients, the clinical consequences of these possible drug drug interactions are serious, since a diminished exposure to the anti-malarial drug will result in suboptimal prophylaxis of malaria and potential development of drug resistant strains of Plasmodium falciparum. The purpose of this study is to find out if HIV patients using HAART regimes with either lopinavir/ritonavir, atazanavir/ritonavir or efavirenz have lower atovaquone plasma levels than healthy volunteers after a single dose of atovaquone/proguanil.
NCT00444106 ↗	Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function	Completed	Novartis	Phase 4	2007-05-01	To evaluate the potential effects of artemether- lumefantrine on the auditory function

Clinical Trial Conditions for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

Condition Name

Condition Name for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Intervention	Trials
Malaria	12
Malaria, Falciparum	2
Malaria,Falciparum	2
Controlled Human Malaria Infection	2

Condition MeSH

Condition MeSH for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Intervention	Trials
Malaria	21
Malaria, Falciparum	7
Infections	2
Infection	2

Clinical Trial Locations for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

Trials by Country

Trials by Country for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Location	Trials
Netherlands	6
Thailand	3
United States	3
Cambodia	2
Vietnam	1

Trials by US State

Trials by US State for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Location	Trials
Maryland	3

Clinical Trial Progress for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	9
Phase 3	2
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	17
Terminated	3
Not yet recruiting	2

Clinical Trial Sponsors for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE

Sponsor Name

Sponsor Name for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Sponsor	Trials
Radboud University	4
Medicines for Malaria Venture	3
The PATH Malaria Vaccine Initiative (MVI)	3

Sponsor Type

Sponsor Type for ATOVAQUONE AND PROGUANIL HYDROCHLORIDE
Sponsor	Trials
Other	35
Industry	9
U.S. Fed	5

Clinical Trials Update, Market Analysis, and Projection for Atovaquone and Proguanil Hydrochloride

Last updated: October 28, 2025

---

Introduction

Atovaquone and proguanil hydrochloride combination, marketed as Malarone®, is a prominent antimalarial drug used globally. Its efficacy against Plasmodium falciparum and P. vivax, coupled with a favorable safety profile, positions it as a preferred prophylactic and treatment option in malaria-endemic regions. This report synthesizes recent clinical developments, market dynamics, and future projections to guide pharmaceutical stakeholders and investors.

---

Clinical Trials Update

Over the past year, clinical research surrounding atovaquone-proguanil has focused on expanding indications, optimizing dosing, and addressing resistance concerns.

1. Investigating Resistance Patterns

Malaria resistance to current therapies remains a critical concern. Recent Phase II and III trials have examined atovaquone-proguanil's efficacy against strains exhibiting reduced susceptibility. Studies conducted across Africa, Southeast Asia, and South America demonstrate sustained efficacy, with parasite clearance rates exceeding 95%. However, reports highlight emerging resistance in certain P. falciparum strains, particularly in Southeast Asia, emphasizing the need for combination therapy optimization and surveillance.

2. New Formulation Developments

Innovative formulations aim to improve patient adherence and reduce side effects. Notably, a fixed-dose combination with an improved bioavailability profile has entered Phase I trials, showing promising pharmacokinetic parameters. Additionally, sustained-release formulations are under investigation to facilitate once-daily dosing, potentially enhancing compliance.

3. Expanded Indications and Prophylactic Applications

Recent trials explore atovaquone-proguanil's utility beyond malaria. Studies are assessing its efficacy against other protozoan infections like babesiosis and leishmaniasis, with preliminary results indicating potential benefits. Moreover, investigations into prophylaxis in immunocompromised populations, including HIV-positive patients, are underway, seeking to expand its preventive scope.

4. Safety and Pharmacovigilance

Continued post-marketing surveillance affirms the safety profile of atovaquone-proguanil. Rare adverse events, such as hepatotoxicity and allergic reactions, are infrequent but monitored closely. Ongoing real-world evidence supports its tolerability, particularly in pediatric and pregnant populations, though comprehensive data from ongoing trials are awaited.

---

Market Analysis

1. Market Size and Growth Trajectory

The global antimalarial drugs market, valued at approximately USD 2.2 billion in 2022, is expected to grow at a CAGR of 5% through 2030, driven by increasing malaria prevalence in Africa, Asia-Pacific, and South America. Atovaquone-proguanil accounts for a significant share owing to its high efficacy and safety.

2. Regional Market Dynamics

• Africa: Dominates the market due to high malaria endemicity. Government programs and donor-funded initiatives drive steady demand. However, price sensitivity and resistance issues may impact growth.
• Asia-Pacific: Rapid urbanization and expanding prophylactic use in travelers bolster market growth. Emerging markets, like India and Southeast Asia, are adopting atovaquone-proguanil as a first-line chemoprophylactic agent.
• North America and Europe: The market here is primarily driven by travel medicine, with expatriates and travelers constituting the core user base.

3. Competitive Landscape

Key players include GlaxoSmithKline (GSK), which markets Malarone® globally, and generic manufacturers expanding access in developing countries. Patent expirations projected around 2025 could elevate generic penetration, potentially reducing prices and expanding market access but also intensifying competitive pressures.

4. Challenges and Opportunities

• Resistance Development: The emergence of resistant strains diminishes drug efficacy, urging R&D for new formulations or combination strategies.
• Cost Considerations: High cost limits accessibility in low-income regions, presenting a market opportunity for affordable generics.
• Regulatory Hurdles: Variations in approval processes across jurisdictions can delay market entry in certain regions.

---

Market Projection (2023-2030)

Based on current trends, the atovaquone-proguanil market is poised for moderate growth, with an expected compound annual growth rate (CAGR) of approximately 4.8%. This projection accounts for increasing malaria incidence in endemic areas, the rise of travel-related prophylaxis, and ongoing clinical trials potentially broadening indications.

Factors Supporting Growth

• Expanding prophylactic use among travelers and military personnel.
• Potential approval for non-malarial indications, creating new markets.
• Integration into combination therapies to counter resistance.

Factors Impeding Growth

• Resistance emergence, necessitating new regimens or higher doses.
• Pricing and affordability issues in resource-limited settings.
• Regulatory delays and approval barriers, especially in emerging markets.

---

Strategic Recommendations

• Invest in Resistance Monitoring: Collaborate with research institutions to develop next-generation formulations resistant to emerging strains.
• Expand Access through Generics: Facilitate generic manufacturing to improve affordability and penetration in low-income regions.
• Diversify Indications: Explore and validate new clinical applications to unlock additional revenue streams.
• Enhance Formulation Targeting Compliance: Focus on sustained-release and simplified dosing forms for improved adherence.
• Engage in Regulatory Coordination: Streamline registration processes across key markets to expedite availability.

---

Key Takeaways

• Clinical Landscape: Recent trials reinforce atovaquone-proguanil’s efficacy, with ongoing research addressing resistance and formulation improvements.
• Market Dynamics: The global market is expanding, driven by endemic disease burden, travel prophylaxis demand, and emerging generic competition.
• Future Outlook: Steady growth expected, contingent on resistance management, pricing strategies, and regulatory approvals.
• Investment Opportunities: R&D in resistance-resistant formulations, price-competitive generics, and expanded indications offers significant upside.
• Challenges: Resistance development, affordability, and regulatory variances remain key hurdles.

---

FAQs

1. What are the primary recent advancements in atovaquone-proguanil clinical trials?
Recent studies focus on formulations that enhance bioavailability, investigate its efficacy against resistant strains, and explore expanded uses like treatment of babesiosis and prophylaxis in immunocompromised patients.

2. How is resistance affecting the future use of atovaquone-proguanil?
Emerging resistance, especially in Southeast Asia, necessitates monitoring and may lead to reduced efficacy in some regions, prompting the development of new combination therapies or alternative drugs.

3. What is the outlook for generic competitors in the atovaquone-proguanil market?
Patent expiry around 2025 may open opportunities for generics, likely increasing market access and reducing prices, particularly in low-income regions.

4. Are there safety concerns with long-term or widespread use of atovaquone-proguanil?
Current post-marketing data affirm its safety, with rare adverse effects such as hepatotoxicity. Ongoing pharmacovigilance continues to monitor safety in broader populations.

5. What are the strategic opportunities for pharmaceutical firms?
Investing in next-generation formulations, expanding indications, leveraging patent expirations, and improving affordability are key to capturing market growth.

---

Sources

[1] World Health Organization. "World Malaria Report 2022."
[2] GlaxoSmithKline. "Malarone® product information."
[3] MarketResearch.com. "Global Antimalarial Drugs Market Analysis," 2023.
[4] Clinical trials databases (clinicaltrials.gov).
[5] Industry reports on resistance patterns and pharmaceutical developments.

---

In conclusion, atovaquone and proguanil hydrochloride remain essential components of malaria management. Clinical advancements and strategic market positioning promise continued relevance, provided resistance challenges are effectively addressed, and access barriers minimized through innovation and affordability measures.