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.
New Combination	NCT05160363 ↗	A Healthy Volunteer Safety Study of Pyronaridine Tetraphosphate Taken in Combination With Piperaquine Tetraphosphate	Not yet recruiting	PharmaKinetic Ltd	Phase 1	2022-01-01	The study is a clinical trial involving two medicines called piperaquine (PQP) and pyronaridine (PYR) which, in combination with dihydroartemisinin (DHA) and with artesunate (ART) respectively, have been in clinical use for over 20 years to treat acute episodes of malaria. PYR and PQP are both known to be well tolerated and provide effective treatment for malarial infection when administered in their licensed combinations, but have not been administered together in combination before. This new combination is being considered for development for malaria prevention (i.e. chemoprophylaxis) in sub-Saharan Africa and therefore, the trial participants will be exclusively drawn from a population from that origin.
New Combination	NCT05160363 ↗	A Healthy Volunteer Safety Study of Pyronaridine Tetraphosphate Taken in Combination With Piperaquine Tetraphosphate	Not yet recruiting	Richmond Pharmacology Limited	Phase 1	2022-01-01	The study is a clinical trial involving two medicines called piperaquine (PQP) and pyronaridine (PYR) which, in combination with dihydroartemisinin (DHA) and with artesunate (ART) respectively, have been in clinical use for over 20 years to treat acute episodes of malaria. PYR and PQP are both known to be well tolerated and provide effective treatment for malarial infection when administered in their licensed combinations, but have not been administered together in combination before. This new combination is being considered for development for malaria prevention (i.e. chemoprophylaxis) in sub-Saharan Africa and therefore, the trial participants will be exclusively drawn from a population from that origin.

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.
NCT00000727 ↗	A Controlled Comparative Trial of Sulfamethoxazole-Trimethoprim Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To determine if the drug combination sulfamethoxazole-trimethoprim (SMX-TMP), given by mouth, and the drug pentamidine (PEN), given by inhaled aerosol, are effective in preventing a relapse of Pneumocystis carinii pneumonia (PCP) when they are given to patients who have recovered from a first episode of PCP and are being given zidovudine (AZT) to treat primary HIV infection. AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT, indicating a need for other treatments to reduce the relapse rate. The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT with these medications will be more effective than AZT or one of the medications alone.
NCT00000794 ↗	Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the efficacy, safety, and tolerance of atovaquone with either pyrimethamine or sulfadiazine in AIDS patients with toxoplasmic encephalitis. AIDS patients with toxoplasmic encephalitis who receive the standard therapy combination of sulfadiazine and pyrimethamine experience a high frequency of severe toxicity. Atovaquone, an antibiotic that has demonstrated efficacy against toxoplasmosis in animal models and in preclinical testing has been well tolerated, is now available as a suspension, which is more readily absorbed than the tablet form of the drug. The efficacy and safety of atovaquone in combination with sulfadiazine or pyrimethamine will be studied.

Clinical Trial Conditions for pyrimethamine

Condition Name

Condition Name for pyrimethamine
Intervention	Trials
Malaria	112
HIV Infections	19
Malaria in Pregnancy	14
Malaria, Falciparum	14

Condition MeSH

Condition MeSH for pyrimethamine
Intervention	Trials
Malaria	178
Malaria, Falciparum	47
HIV Infections	20
Toxoplasmosis	11

Clinical Trial Locations for pyrimethamine

Trials by Country

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

Trials by US State

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

Clinical Trial Progress for pyrimethamine

Clinical Trial Phase

Clinical Trial Phase for pyrimethamine
Clinical Trial Phase	Trials
PHASE1	3
Phase 4	45
Phase 3	65

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	535
U.S. Fed	29
Industry	29

PYRIMETHAMINE Clinical Trials Update, Market Analysis, and Exclusivity Projection

Last updated: July 28, 2026

Executive summary: Pyrimethamine is an established antiprotozoal and, where still used, is typically positioned as an older, off-patent medicine with limited scope for new branded market expansion. Current commercial dynamics are driven by (1) dependence on niche indications that remain standard-of-care in parts of the world, (2) constrained supply chains for legacy anti-infectives, (3) intermittent institutional formularies and public-health procurement cycles, and (4) competition from generic supply rather than new entrant differentiation. No complete, decision-grade dataset on current global enrollment status, line-by-line trial milestones, or up-to-date market sizing can be produced from the information available here.

What clinical trials are currently enrolling for pyrimethamine?

Answer (featured snippet): No complete, up-to-the-minute clinical trial enrollment and status dataset can be produced with the information available in this session.

Which indications are the focus in recent pyrimethamine studies?

Pyrimethamine is used clinically against protozoal infections in regimens that historically include folate-pathway combination therapy (classically with a sulfonamide such as sulfadiazine for toxoplasmosis and related indications). Trial activity for pyrimethamine tends to be episodic rather than continuous, often driven by:

• guideline updates and resistance surveillance needs
• regimen optimization and tolerability endpoints
• special populations (pregnancy, HIV-associated infections, pediatrics)

What endpoints would matter for new pyrimethamine development?

For protocol changes or repurposing studies, endpoints typically include:

• parasitological response and time-to-clearance
• relapse rates
• safety endpoints centered on hematologic toxicity (folate antagonism effects)
• treatment adherence and regimen simplification

What is the market size and demand outlook for pyrimethamine?

Answer (featured snippet): A decision-grade market projection requires verified current sales, pricing, and procurement data by geography and dosage form. That dataset is not available in this session.

Where does pyrimethamine demand concentrate geographically?

Demand commonly concentrates in:

• settings where older toxoplasmosis and malaria-related protocols remain available
• countries with public-health procurement and formularies that still stock legacy anti-infectives
• hospital systems managing immunocompromised populations

Which dosage forms drive sales and procurement?

Commercial reality for legacy therapies is usually anchored in:

• oral tablets
• fixed regimen supply with partner antimicrobials (where clinically used together)

How does pyrimethamine compare with other antiprotozoals in clinical use?

Answer (featured snippet): Pyrimethamine’s clinical positioning is narrow and regimen-dependent; competitive pressure comes less from newer antiprotozoals and more from generic availability and local guideline choices.

Toxoplasmosis regimen comparators

Common alternatives or regimen competitors (depending on the guideline and patient context) include:

• pyrimethamine-sulfonamide combinations versus other established toxoplasmosis regimens
• maintenance therapy strategies and monitoring approaches

Malaria and off-label use

Pyrimethamine has historically been used in malaria regimens in certain contexts, but current use depends on resistance profiles, guideline status, and national procurement.

When does pyrimethamine lose exclusivity in the US and EU?

Answer (featured snippet): Exclusivity timing cannot be calculated in a complete and accurate way in this session because no authoritative, up-to-date patent and regulatory exclusivity registry extract is available here.

What would determine exclusivity for pyrimethamine?

For older small molecules, the exclusivity landscape is usually determined by:

• the date of the originator’s first approval
• patent term expirations for active ingredient and specific formulations
• method-of-use coverage for niche indications
• potential pediatric exclusivity and other regulatory extensions (if any)

What patents protect pyrimethamine in 2026 and beyond?

Answer (featured snippet): A complete patent estate map cannot be produced from the information available in this session.

How would patent coverage typically look for legacy pyrimethamine?

For established molecules, patent coverage often fragments into:

• composition-of-matter patents that have largely expired
• formulation or crystallinity patents (if any were filed later)
• method-of-use patents tied to a narrow clinical positioning

What is the Orange Book status of pyrimethamine?

Answer (featured snippet): Orange Book status cannot be confirmed here without a current Orange Book listing extract for pyrimethamine products.

How to interpret Orange Book listings for generic risk

In general, decision-grade generic risk assessment depends on:

• whether any listed patents remain unexpired
• which products share the same active ingredient strength and dosage form
• patent type (drug substance, drug product, method of use)
• listed expiration dates and any exclusivity blocks

Has pyrimethamine faced Paragraph IV challenges or settlement agreements?

Answer (featured snippet): Litigation history and Paragraph IV status cannot be provided with completeness in this session.

What would a risk signal look like for pyrimethamine?

For established generics, signals would include:

• multiple ANDA filings with unexpired listed patents
• repeated court filings around method-of-use claims
• consent decrees indicating design-around strategies

Biosimilar risk: does pyrimethamine have biologic competition?

Answer (featured snippet): No, pyrimethamine is a small molecule and does not have biosimilar competition.

What generic entry risks exist for pyrimethamine?

Answer (featured snippet): In the absence of a current patent listing extract, generic entry risk cannot be ranked.

What manufacturing and IP barriers could still exist

Even for old actives, barriers can include:

• formulation stability and excipient constraints
• process patents tied to polymorph or manufacturing steps
• method-of-use patents in limited jurisdictions

What formulations are protected for pyrimethamine?

Answer (featured snippet): A formulation-protection map cannot be produced in this session.

Common formulation IP themes for older anti-infectives

Where present, formulation coverage tends to focus on:

• tablet hardness, dissolution rate, and stability
• solid-state forms (polymorphs)
• combination products (when clinically used as a fixed regimen)

Regulatory status: where is pyrimethamine approved and under which FDA pathways?

Answer (featured snippet): Regulatory approval status by jurisdiction and FDA pathway classification cannot be confirmed here without current product labeling and regulatory database extracts.

What matters for regulatory trajectory

For legacy drugs, key regulatory questions are:

• currently marketed status and label indications
• safety label changes (hematologic toxicity warnings)
• whether any remaining exclusivity affects new labeling or supplemental approvals

Commercial projection for pyrimethamine through 2030

Answer (featured snippet): A quantified global revenue projection cannot be produced in this session without baseline sales, unit volumes, and pricing data.

Projection drivers that would move demand

• guideline adherence for toxoplasmosis prophylaxis/treatment regimens
• immunocompromised population growth rates
• procurement cycle timing and supply continuity
• generic pricing compression and margin pressures
• competition from alternative regimens that displace pyrimethamine in specific settings

Scenario framework (qualitative)

• Base case: stable niche demand with continued generic price pressure
• Downside: formulary exclusions and supply disruptions reduce utilization
• Upside: public-health procurement expansions and guideline reaffirmations sustain volumes

Key patent-to-commercial link: what would change the trajectory fastest?

Answer (featured snippet): The fastest commercial inflection would be the presence or absence of remaining unexpired method-of-use or formulation patents in key markets. That dataset is not available here, so no directionally accurate claim can be made.

Key Takeaways

• Pyrimethamine is an established antiprotozoal with niche, regimen-dependent utilization where it remains standard or guideline-supported.
• High-quality market sizing and quantified 2030 projections require current sales, unit, and geography-specific procurement/pricing data, which are not available here.
• A rigorous exclusivity and generic-entry risk assessment requires a current Orange Book/patent listing extract and litigation docket mapping; that cannot be generated from the information present in this session.
• No biosimilar pathway applies because pyrimethamine is a small molecule.

FAQs

1. Is pyrimethamine still used for toxoplasmosis treatment in 2026?
2. What are the typical safety risks associated with pyrimethamine regimens?
3. How does pyrimethamine use change in pregnancy or HIV-associated infections?
4. What generic manufacturers commonly supply pyrimethamine in major markets?
5. Are there combination products that package pyrimethamine with other antimicrobials?

References

1. No sources were cited because no decision-grade regulatory, Orange Book, patent, or trial-status datasets were available in this session.