CLINICAL TRIALS PROFILE FOR PYRIMETHAMINE

505(b)(2) Clinical Trials for Pyrimethamine

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	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	Global Fund	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	Medical Research Council, South Africa	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	World Health Organization	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	University of Cape Town	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT03431168 ↗	A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV	Active, not recruiting	University of Alabama at Birmingham	Phase 2	2018-03-07	More than 3 billion people worldwide are at risk of acquiring malaria and pregnant women living with HIV in Africa are at particular risk. An effective prophylaxis regimen capable of preventing malaria and other common perinatal infections would have great potential to improve adverse birth outcomes. The purpose of this randomized controlled trial is to evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to determine its efficacy and safety.

All Clinical Trials for Pyrimethamine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000643 ↗	Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in HIV-infected patients. Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients.
NCT00000666 ↗	A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii. Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine. Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	Glaxo Wellcome	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	Upjohn	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Clinical Trial Conditions for Pyrimethamine

Condition Name

Condition Name for Pyrimethamine
Intervention	Trials
Malaria	112
HIV Infections	18
Malaria in Pregnancy	14
Malaria, Falciparum	14

Condition MeSH

Condition MeSH for Pyrimethamine
Intervention	Trials
Malaria	178
Malaria, Falciparum	47
HIV Infections	19
Toxoplasmosis	11

Clinical Trial Locations for Pyrimethamine

Trials by Country

Trials by Country for Pyrimethamine
Location	Trials
United States	87
Tanzania	20
Malawi	19
Mali	16
Uganda	16

Trials by US State

Trials by US State for Pyrimethamine
Location	Trials
New York	11
California	9
Maryland	8
Florida	5
Ohio	4

Clinical Trial Progress for Pyrimethamine

Clinical Trial Phase

Clinical Trial Phase for Pyrimethamine
Clinical Trial Phase	Trials
Phase 4	45
Phase 3	65
Phase 2/Phase 3	13

Clinical Trial Status

Clinical Trial Status for Pyrimethamine
Clinical Trial Phase	Trials
Completed	157
Not yet recruiting	16
Unknown status	14

Clinical Trial Sponsors for Pyrimethamine

Sponsor Name

Sponsor Name for Pyrimethamine
Sponsor	Trials
London School of Hygiene and Tropical Medicine	66
Centers for Disease Control and Prevention	25
Gates Malaria Partnership	23

Sponsor Type

Sponsor Type for Pyrimethamine
Sponsor	Trials
Other	531
U.S. Fed	29
Industry	28

Pyrimethamine: Clinical Trials, Market Analysis, and Projections

Introduction to Pyrimethamine

Pyrimethamine is an antiparasitic drug that has been widely used to treat and prevent protozoan and toxoplasma infections. Recently, it has also been explored for its potential in treating other conditions, including certain types of cancer.

Clinical Trials Update

STAT3 Inhibition in CLL

One of the notable clinical trials involving pyrimethamine is its use as a STAT3 inhibitor in patients with chronic lymphocytic leukemia (CLL). STAT3 is an oncogenic transcription factor that is constitutively activated in CLL cells. The trial aimed to determine whether pyrimethamine, known for its safety in humans, could inhibit STAT3-dependent gene expression and confer clinical benefit in CLL patients.

• Trial Design: The phase I clinical trial involved 16 heavily pretreated CLL patients who received continuous daily pyrimethamine in doses of 12.5, 25, and 50 mg per day. The trial used a 3+3 dose escalation design[1].
• Outcomes: While no dose-limiting toxicities or significant drug-related toxicities were observed, there were no objective responses by IW-CLL 2008 criteria. However, half of the patients achieved stable disease, with one patient on 50 mg/day remaining on therapy for 12 months and two patients on 25 mg/day for 4 and 6 months, respectively[1].
• Pharmacodynamics: The study found that plasma concentrations of pyrimethamine correlated closely with dose levels, but only the highest dose cohort approached the threshold necessary for consistent STAT3 inhibition in vitro. The expression of STAT3-dependent genes in CLL cells was also monitored, suggesting that higher doses might be necessary to achieve an on-target therapeutic effect[1].

Other Clinical Trials

In addition to its use in CLL, pyrimethamine is being explored in other clinical trials, such as those involving human papillomavirus (HPV)-related diseases. These trials are in the early phases and are testing the safety, side effects, and biological activity of pyrimethamine in various patient populations[4].

Market Analysis

Current Market Size and Growth

The global pyrimethamine market was valued at USD 1,106.8 million in 2021 and is projected to grow to USD 1,792.0 million by 2030, at a Compound Annual Growth Rate (CAGR) of 5.5% during the forecast period[2][3].

Regional Market Segmentation

• North America: This region currently holds the largest market share, driven by the presence of major pharmaceutical companies, high levels of research and development investment, and significant healthcare spending. North America accounted for around 37% of the market share in 2021[2][3][5].
• Asia-Pacific: This region is expected to grow at the fastest CAGR during the forecast period due to increasing government awareness campaigns, rising income levels, and a growing patient population. Countries like China and India are key drivers of this growth[2][3][5].

Application and Indication

• Hospitals and Clinics: Hospitals dominate the market with the largest share, primarily because pyrimethamine is often used to treat protozoan and toxoplasma infections in a hospital setting[3].
• Malaria: The malaria segment contributes the highest share among therapeutic indications, driven by the widespread endemicity of malaria globally. According to the WHO, malaria imposes a significant disease burden, particularly in developing tropical countries[5].

Market Projections

Drivers of Growth

• Increasing Prevalence of Malaria and HIV: The rising number of people living with HIV and the increasing prevalence of malaria are significant drivers of the pyrimethamine market. Immunocompromised individuals are more susceptible to infections, which increases the demand for pyrimethamine[2][3][5].
• Research and Development: Continuous investments in research and development by major pharmaceutical companies, especially in regions like North America, are expected to enhance the market growth[5].

Challenges

• Stringent Regulatory Guidelines: One of the primary challenges facing the pyrimethamine market is the stringent regulatory guidelines that govern drug approval processes. These regulations can delay clinical research and hinder timely market entry for new formulations or indications[5].
• Parasite Resistance: The development of parasite resistance to existing drugs is another challenge that could hamper market growth[5].

Opportunities

• New Therapeutic Applications: Ongoing research is exploring the efficacy of pyrimethamine in treating other parasitic infections and as an adjunct therapy for certain cancers. Successful outcomes in these areas could expand its therapeutic scope and demand[5].

Key Takeaways

• Clinical Trials: Pyrimethamine shows promise as a STAT3 inhibitor in CLL, though higher doses may be necessary for optimal therapeutic effect.
• Market Growth: The global pyrimethamine market is expected to grow at a CAGR of 5.5% from 2021 to 2030, driven by increasing prevalence of malaria and HIV, and significant research and development investments.
• Regional Dominance: North America currently holds the largest market share, while the Asia-Pacific region is expected to grow the fastest.
• Challenges and Opportunities: The market faces challenges such as stringent regulatory guidelines and parasite resistance, but also presents opportunities for new therapeutic applications.

FAQs

What is the primary use of pyrimethamine?

Pyrimethamine is primarily used to treat and prevent protozoan and toxoplasma infections.

What is the current market size of pyrimethamine?

The global pyrimethamine market was valued at USD 1,106.8 million in 2021.

What is the projected growth rate of the pyrimethamine market?

The market is expected to grow at a CAGR of 5.5% from 2021 to 2030.

Which region dominates the pyrimethamine market?

North America currently holds the largest market share, driven by significant pharmaceutical companies and high healthcare spending.

What are the main drivers of the pyrimethamine market growth?

The increasing prevalence of malaria and HIV, along with significant research and development investments, are key drivers of the market growth.

What challenges does the pyrimethamine market face?

The market faces challenges such as stringent regulatory guidelines and the development of parasite resistance to existing drugs.

Sources

1. A Clinical Trial of the STAT3 Inhibitor Pyrimethamine in Chronic Lymphocytic Leukemia. Blood, 2018.
2. Global Pyrimethamine Market Size to grow USD 1792 Million by 2030 | CAGR of 5.5%. GlobeNewswire, 2022.
3. Pyrimethamine Market Size, Trend during Forecast 2030. Spherical Insights, 2023.
4. Clinical Trials Using Pyrimethamine. National Cancer Institute, 2023.
5. Pyrimethamine Market - Report, Trends, Share & Insights. Coherent Market Insights, 2023.

Last updated: 2024-12-31