CLINICAL TRIALS PROFILE FOR PRIMAQUINE

505(b)(2) Clinical Trials for PRIMAQUINE

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 Formulation	NCT05788094 ↗	DHA-PPQ vs CHQ With Tafenoquine for P. Vivax Mono-infection	Not yet recruiting	Mahidol Oxford Tropical Medicine Research Unit	Phase 4	2023-04-01	In this area of Greater Mekong Subregion (GMS), vivax malaria is the most common kind of malaria. It can stay very long in the liver, and come out later to make another episode of illness. This can happen many times even without a mosquito bite. Only 8-aminoquinoline drugs can kill the liver forms of the malaria parasite. One of these drugs is called primaquine, and it has been used all over the world for a long time. There is now a new formulation of this 8-aminoquinoline drug called tafenoquine that can also treat the malaria in the liver. The main benefit of this drug is that it is a single dose, which makes much convenient for the patients as well as for the malaria control program than conventional 14 days of primaquine. Recent research suggests that ACT (Artemisinin Combination Therapy) may antagonise the efficacy of tafenoquine (Baird et al. 2020) . This could prevent the use of tafenoquine in areas with chloroquine resistant P. vivax parasites where national malaria programmes recommend ACTs for vivax malaria. Also, currently recommended tafenoquine dose is sub-optimal: 300 mg dose proved significantly inferior to low dose primaquine in a meta-analysis of the phase 3 studies when restricted to the Southeast Asian region (Llanos-Cuentas et al. 2019; Watson et al. 2022). A tafenoquine dose of 450mg is predicted to provide >90% of the maximal effect. The objective of this research is to find out whether 450 mg dose of tafenoquine can be combined effectively with ACT providing a short course treatment for P. vivax malaria.
New Formulation	NCT05788094 ↗	DHA-PPQ vs CHQ With Tafenoquine for P. Vivax Mono-infection	Not yet recruiting	Shoklo Malaria Research Unit	Phase 4	2023-04-01	In this area of Greater Mekong Subregion (GMS), vivax malaria is the most common kind of malaria. It can stay very long in the liver, and come out later to make another episode of illness. This can happen many times even without a mosquito bite. Only 8-aminoquinoline drugs can kill the liver forms of the malaria parasite. One of these drugs is called primaquine, and it has been used all over the world for a long time. There is now a new formulation of this 8-aminoquinoline drug called tafenoquine that can also treat the malaria in the liver. The main benefit of this drug is that it is a single dose, which makes much convenient for the patients as well as for the malaria control program than conventional 14 days of primaquine. Recent research suggests that ACT (Artemisinin Combination Therapy) may antagonise the efficacy of tafenoquine (Baird et al. 2020) . This could prevent the use of tafenoquine in areas with chloroquine resistant P. vivax parasites where national malaria programmes recommend ACTs for vivax malaria. Also, currently recommended tafenoquine dose is sub-optimal: 300 mg dose proved significantly inferior to low dose primaquine in a meta-analysis of the phase 3 studies when restricted to the Southeast Asian region (Llanos-Cuentas et al. 2019; Watson et al. 2022). A tafenoquine dose of 450mg is predicted to provide >90% of the maximal effect. The objective of this research is to find out whether 450 mg dose of tafenoquine can be combined effectively with ACT providing a short course treatment for P. vivax malaria.

All Clinical Trials for PRIMAQUINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	Glaxo Wellcome	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	Jacobus Pharmaceutical	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000640 ↗	A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.
NCT00000717 ↗	The Safety and Efficacy of Clindamycin and Primaquine in the Treatment of Mild - Moderate Pneumocystis Carinii Pneumonia in Patients With AIDS	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To determine the safety and effectiveness of clindamycin and primaquine in the treatment of mild Pneumocystis carinii pneumonia (PCP) in AIDS patients. As many as 80 percent of AIDS patients experience at least one episode of PCP and about one-third of these patients have a recurrence of the disease. Drugs currently used for treatment of acute PCP are toxic to the majority of AIDS patients. The combination of clindamycin and primaquine reduces the numbers of PCP organisms in laboratory tests and in animal studies. Both drugs can be given orally, concentrate in lung tissue, and have been used safely in humans for treatment of other diseases. It is possible that the combination may prove to be as good or better than standard therapy for PCP and side effects may be less.
NCT00076323 ↗	A Test to Predict the Hemolytic Potential of Drugs in G6PD Deficiency	Completed	Walter Reed Army Institute of Research (WRAIR)	N/A	2003-12-01	This study will evaluate a new and safe testing method for identifying medicines that can cause problems in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. We are looking for volunteers with G6PD deficiency who would be willing to donate blood samples.
NCT00158548 ↗	ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan	Completed	HealthNet TPO	Phase 3	2001-06-01	Chloroquine resistant falciparum malaria in Pakistan is prevalent in every malarious area examined. Resistance to the favoured second-line treatment, sulphadoxine-pyrimethamine S/P is rising fast. To avert a repetition of the resistance catastrophe that occurred in SE Asia it is critical to preserve the effective life of SP by using it in combination with artesunate. Efficacy of ACT with artesunate in combination with chloroquine, SP or amodiaquine for treatment of malaria (falciparum or vivax) will be examined in malaria patients in Pakistan.
NCT00158548 ↗	ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan	Completed	Malaria Control Program, Directorate of Malaria Control, Pakistan	Phase 3	2001-06-01	Chloroquine resistant falciparum malaria in Pakistan is prevalent in every malarious area examined. Resistance to the favoured second-line treatment, sulphadoxine-pyrimethamine S/P is rising fast. To avert a repetition of the resistance catastrophe that occurred in SE Asia it is critical to preserve the effective life of SP by using it in combination with artesunate. Efficacy of ACT with artesunate in combination with chloroquine, SP or amodiaquine for treatment of malaria (falciparum or vivax) will be examined in malaria patients in Pakistan.

Clinical Trial Conditions for PRIMAQUINE

Condition Name

Condition Name for PRIMAQUINE
Intervention	Trials
Malaria	48
Vivax Malaria	20
Malaria, Vivax	16
Malaria,Falciparum	8

Condition MeSH

Condition MeSH for PRIMAQUINE
Intervention	Trials
Malaria	109
Malaria, Vivax	44
Malaria, Falciparum	30
Glucosephosphate Dehydrogenase Deficiency	8

Clinical Trial Locations for PRIMAQUINE

Trials by Country

Trials by Country for PRIMAQUINE
Location	Trials
Thailand	35
United States	27
Cambodia	17
Brazil	15
Indonesia	13

Trials by US State

Trials by US State for PRIMAQUINE
Location	Trials
Mississippi	3
Maryland	3
California	3
Washington	2
Ohio	2

Clinical Trial Progress for PRIMAQUINE

Clinical Trial Phase

Clinical Trial Phase for PRIMAQUINE
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	1
PHASE2	1

Clinical Trial Status

Clinical Trial Status for PRIMAQUINE
Clinical Trial Phase	Trials
Completed	88
Not yet recruiting	12
Recruiting	12

Clinical Trial Sponsors for PRIMAQUINE

Sponsor Name

Sponsor Name for PRIMAQUINE
Sponsor	Trials
University of Oxford	35
Menzies School of Health Research	17
Mahidol Oxford Tropical Medicine Research Unit	16

Sponsor Type

Sponsor Type for PRIMAQUINE
Sponsor	Trials
Other	358
Industry	28
U.S. Fed	19

Primaquine clinical trials update, market analysis and exclusivity outlook (R&D, generic and regulatory risk)

Last updated: July 28, 2026

What is the current clinical trial landscape for primaquine (any sponsor, phase, and key endpoints)?

Primaquine is an established antimalarial used for P. vivax and P. ovale relapse prevention (radical cure) and for P. falciparum gametocytocidal activity. Current “primaquine” clinical activity is dominated by (1) safety/tolerability work tied to G6PD deficiency risk, and (2) regimen comparisons meant to improve real-world adherence and reduce total dosing burden.

What trial types most commonly appear for primaquine

• G6PD-stratified safety: incidence of hemolysis and clinically significant anemia by baseline G6PD status.
• Pharmacokinetics (PK) and food effect: absorption, exposure variability, and dose normalization.
• Adherence-oriented regimens: single-dose vs multi-dose course comparisons; fixed adherence pathways in endemic settings.
• Alternative dosing strategies: dose fractionation, extended-course approaches, and attempts to preserve efficacy while reducing hematologic events.

What “current update” means in practice for primaquine Because primaquine is older and widely used, the clinical pipeline tends to be incremental rather than new-combination phase programs. The most commercially relevant trials are those that can support:

• updated labeling aligned to point-of-care G6PD testing workflows,
• dosing regimens that are easier to administer at scale,
• and safety evidence adequate for broad deployment in public programs.

Clinical trial endpoints that drive label expansion and purchasing decisions

• hemolysis markers and anemia incidence
• hospitalization rates related to adverse hematologic outcomes
• treatment completion rates and days on therapy
• PK exposure metrics tied to efficacy and safety proxies
• efficacy against liver-stage relapse (measured by confirmed radical cure rates over follow-up periods)

What market size and demand drivers exist for primaquine (where revenue concentrates)?

Primaquine demand is driven by:

• malaria epidemiology with significant vivax burden,
• national malaria program procurement practices,
• and the ability to implement G6PD testing (or to manage risk without reliable testing).

Primary demand segments

1. Radical cure programs for P. vivax and P. ovale
2. Transmission reduction programs using gametocytocidal dosing for P. falciparum (as a component of broader combination strategies)
3. Private-sector supply in endemic markets where testing adoption varies

Market levers that increase or suppress unit consumption

• adoption rate of G6PD testing and point-of-care kits
• procurement guideline changes from WHO and national programs
• drug availability and price stability for older generic inventory
• distribution constraints for small, tablet-based dosing regimens

When do primaquine patents expire and when does exclusivity end (timeline by regulatory exclusivity type)?

Primaquine is a long-circulating generic molecule, so the “exclusivity” story is largely about:

• new fixed-dose combinations (if any),
• new salt/formulation patents (if present),
• and regulatory exclusivity in the US tied to new NDA/505(b)(2) products (if any exist).

Practical exclusivity framing for an established active

• If the marketed product is an Abbreviated New Drug Application (ANDA) without a reference-product exclusivity stack, the commercial timeline typically follows patent-by-patent expiration rather than a single end date.
• If a company pursued a 505(b)(2) pathway for a new formulation or labeled dosing approach, exclusivity may come from the underlying regulatory pathway and data exclusivity periods, but these are product-specific.

Which patents protect primaquine (active ingredient, formulation, method-of-use, and manufacturing)?

For an older small-molecule like primaquine, the protected landscape is usually fragmented into:

• formulation patents (coatings, excipients, particle size, stability),
• method-of-use patents (specific dosing strategies, G6PD testing-aligned regimens),
• and manufacturing process patents (granulation, solid-state control, dissolution specs).

Patent estate structure that matters for enforcement

• Method-of-use claims tied to vivax radical cure relapse prevention or gametocytocidal use
• Dosing algorithms contingent on G6PD status or testing thresholds
• Solid oral dosage patents (immediate release formulation specs)
• Process patents aimed at controlling impurity profiles and stability

What is the Orange Book status of primaquine (listed patents, exclusivity, and label-relevant claims)?

Orange Book status is the decisive registry for US market exclusivity because it lists:

• approved drug products,
• patents that claim the drug substance, drug product, or method of use,
• and patent expiration dates.

How to interpret Orange Book for primaquine

• If multiple ANDAs exist, the Orange Book entry list becomes a map of which companies’ products and patent thickets control generic launch timing.
• If patents are listed, the key question is whether they are:
  • substance/product patents (hard barriers to generic substitution), or
  • method-of-use patents (potential design-around via labeling carve-outs or different dosing indications).

What patent litigation affects primaquine (generic risks, Paragraph IV, settlements)?

For long-established actives, US patent litigation tends to be:

• sporadic,
• focused on formulation or method-of-use remnants,
• or resolved via settlements that control launch timing for specific generic label scopes.

Paragraph IV risk profile for an established drug

• If any Orange Book-listed patents still have active terms, a generic filing may trigger:
  • notice letters and counterclaims on listed method-of-use indications,
  • potential “carve-out” labels,
  • and settlement-driven launch dates.

Commercially relevant litigation signals

• settlement dates and agreed entry triggers for specific ANDA applicants
• court rulings narrowing method-of-use coverage
• stipulations that effectively alter label content or dosing language

How does primaquine compare with tafenoquine and other relapse-prevention alternatives (market substitution risk)?

Tafenoquine is the closest market substitute for vivax relapse prevention because it can be positioned as:

• single-dose convenience relative to multi-dose primaquine courses,
• and sometimes simplified adherence.

Competitive substitution dynamics

• Where health systems can deploy G6PD testing reliably, tafenoquine adoption can accelerate because of simplified dosing.
• Where testing is limited, adoption depends on the feasibility of safe screening pathways and guideline language.

Implication for primaquine market projections

• Primaquine remains an anchor therapy, but growth is capped by:
  • shifting guideline preferences,
  • unit cost and procurement competitiveness,
  • and the relative administrative burden versus alternatives.

What formulation and dosing strategies are protected (what could block generic design-around)?

The main design-around constraints for primaquine generics are not the active itself but:

• formulation patents governing stability or dissolution characteristics,
• excipient systems controlling release and impurity formation,
• and method-of-use patents tied to specific dosing regimens.

Common formulation features that can be claim targets

• controlled-release vs immediate-release (if claimed separately, though primaquine is typically immediate release)
• particle size distribution and dissolution rate windows
• impurity control methods validated through stability studies
• packaging/stability requirements that align with shelf-life specifications

Which companies compete in primaquine (US and high-burden markets)?

Primaquine is typically supplied by multiple generics in endemic countries. The most actionable competitive view is:

• which suppliers dominate tender awards,
• whether procurement agencies prefer specific dosing formats,
• and which firms have the most favorable price and supply stability.

Market structure pattern

• US: multiple ANDAs and generic competition
• Endemic procurement: fewer suppliers per tender, with price and supply certainty driving selection

What generic entry risks exist for primaquine (launch scenarios and timing drivers)?

Generic entry timing is governed by:

• Orange Book patent term expirations (product and method-of-use),
• any listed patents still enforceable in relevant jurisdictions,
• ANDA filing status and litigation outcomes.

Scenario-based timing that matters to investors

• Unblocked launch: no active enforceable patents, or patents expire before market entry.
• Label carve-out entry: launch with narrowed method-of-use indication that avoids infringement theories.
• Settlement-triggered entry: launch permitted after agreed date.
• Injunction risk: launch delayed where method-of-use coverage remains disputed and not narrowed.

How strong is the patent estate for primaquine (freedom-to-operate lens)?

For an older active, patent strength usually compresses to:

• a small number of still-active formulation/method-of-use patents, or none
• and broad generic freedom when no enforceable Orange Book-listed patents survive.

Freedom-to-operate depends on jurisdiction and specific product

• US: Orange Book controls “listed patent” risk for market entry
• Key export markets: national filings and enforcement vary widely, and litigation intensity tends to be lower than in the US unless a premium product differentiates itself

How does FDA regulatory status shape commercialization for primaquine?

Primaquine’s FDA status matters mainly for:

• whether products are approved under ANDA or 505(b)(2),
• the exact labeled indication language (radical cure and gametocytocidal use),
• and any label updates tied to G6PD testing or warnings.

Regulatory factors that influence purchasing and adoption

• label alignment with WHO-recommended safety handling
• clarity on G6PD test requirements
• dosing schedules supported by safety and efficacy evidence

What is the commercialization projection for primaquine through 2030 (base-case and downside)?

A defensible projection for primaquine depends on:

• malaria case trends and vivax relapse prevalence,
• procurement budgets and access programs,
• adoption of single-dose alternatives (notably tafenoquine),
• and the degree to which G6PD testing penetration expands safe use.

Base-case projection logic

• Unit demand stays resilient because radical cure for vivax/ovale remains standard of care.
• Growth is largely volume-driven rather than price-driven because generics compress margins.

Downside drivers

• faster-than-expected substitution toward single-dose alternatives
• failure to scale safe G6PD testing access, reducing the fraction of treated patients eligible for primaquine
• supply disruptions or tender preference changes

Upside drivers

• improved point-of-care G6PD testing adoption
• guideline updates reinforcing primaquine where alternatives are constrained by cost or supply
• expanded use in transmission reduction programs where primaquine dosing is compatible with local protocols

Key takeaways

• Primaquine clinical activity is mostly incremental: safety in G6PD-stratified populations, dosing/regimen refinements, and PK work supporting label-relevant improvements.
• Market demand is anchored in vivax/ovale relapse prevention and is shaped by the ability to implement G6PD testing safely.
• Exclusivity timing is not driven by a single “primaquine patent end date” as much as by any still-active product- or method-of-use patents tied to specific approved formulations and labeled regimens.
• Generic entry risk in the US is determined by Orange Book-listed patents for individual approved products and by any Paragraph IV litigation/settlement history.
• Competitive pressure comes from single-dose alternatives (notably tafenoquine), with substitution speed dependent on testing availability, guideline language, and procurement economics.

FAQs

1. Do primaquine dosing regimens differ by G6PD status in current labeling and clinical evidence?
2. Are there US FDA exclusivities tied to any primaquine product reformulation or new dosing approach?
3. Which Orange Book patents are most likely to block generic entry for primaquine products?
4. How does tafenoquine adoption affect primaquine procurement volumes in high-vivax countries?
5. What formulation or manufacturing changes are most likely to support generics without altering labeled method-of-use risk?

References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (Drug entries for primaquine-containing products). U.S. Food and Drug Administration.
2. WHO. Guidelines for malaria treatment and related anti-relapse therapy recommendations (primaquine/treatment of P. vivax and P. ovale). World Health Organization.
3. ClinicalTrials.gov. Primaquine clinical trials registry (sponsor, phase, recruitment status, endpoints). National Library of Medicine.