CLINICAL TRIALS PROFILE FOR NALIDIXIC ACID

All Clinical Trials for Nalidixic Acid

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00741052 ↗	Ciprofloxacin Multiple Dose for Adult Cholera	Completed	International Centre for Diarrhoeal Disease Research, Bangladesh	Phase 3	2007-07-01	Cholera is an important diarrhoeal disease and an important cause of death, particularly during epidemic outbreaks, in Bangladesh and many other developing countries. Used as an adjunct to management of dehydration, antimicrobial therapy using an appropriate agent reduces diarrhoea duration and stool volume in severe cholera by about half. The usefulness of antimicrobials has, however, been greatly eroded by the increasing prevalence of resistant strains of V. cholerae O1. From October 2004 at the Matlab Hospital and from December 2004 at the Dhaka Hospital of ICDDR, B, V. cholerae strains became increasingly resistant to tetracycline and erythromycin- two drugs used in the treatment of severe cholera in adults and children respectively. Because of this high prevalence of resistance we resorted in early 2005 to using ciprofloxacin for treatment against multi drug resistant V. cholerae. Although all isolates were susceptible to ciprofloxacin when standard thresholds for disc-diffusion or E-test were used, but majority of the strains demonstrated a MIC value of 0.250 µg/ml, over hundred-folds greater than the V. cholerae strains tested in earlier years, which generally had a MIC of <0.003 µg/ml. In this randomized, double blind, controlled trial we will assess clinical and bacteriological response to 12 hourly oral dose of ciprofloxacin for 3 days in which the first two doses will be 1 g each and the later 4 doses will be 500 mg each, and compare them with a single 1 g oral dose of azithromycin. We are using azithromycin as the comparator drug because current circulating V. cholerae isolates are susceptible (MIC ≤ 0.125 µg/ml) to this azithromycin, and single-dose azithromycin has been evaluated earlier to be effective in the treatment of cholera.
NCT01335334 ↗	H. Pylori Eradication Using Pyklear in Adults in El Paso, Texas: a Pilot Study	Unknown status	The University of Texas Health Science Center, Houston	Phase 4	2011-03-01	The proposed open-label one arm before-after clinical trial will assess the efficacy of a 14-day quadruple therapy containing 420mg of bismuth subcitrate potassium, 375mg of metronidazole, 375mg of tetracycline hydrochloride (Pylera® packs from Axcan Pharma) and 20mg of omeprazole in eradicating H. pylori infection in 50 asymptomatic adults in El Paso, Texas. As part of the study we will obtain specimens for culture of H. pylori in a reference laboratory.
NCT01804634 ↗	Reduced Intensity Haploidentical BMT for High Risk Solid Tumors	Recruiting	Sidney Kimmel Comprehensive Cancer Center	Phase 2	2013-03-27	The purpose of this study is to see if giving reduced intensity chemotherapy, haploidentical bone marrow, post-transplant cyclophosphamide and shortened duration tacrolimus is safe and feasible for patients with very high-risk solid tumors.
NCT01804634 ↗	Reduced Intensity Haploidentical BMT for High Risk Solid Tumors	Recruiting	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Phase 2	2013-03-27	The purpose of this study is to see if giving reduced intensity chemotherapy, haploidentical bone marrow, post-transplant cyclophosphamide and shortened duration tacrolimus is safe and feasible for patients with very high-risk solid tumors.
NCT02017197 ↗	Therapeutic Equivalence Between Branded and Generic WARFArin Tablets in Brazil	Completed	Fundação de Amparo à Pesquisa do Estado de São Paulo	Phase 4	2014-08-01	The purpose of this study is to assess whether the switch from branded to generic warfarin or between different generic warfarin tablets may cause fluctuation in the results of coagulation tests (International Normalized Rate, acronym INR) in patients, thus predisposing them to unnecessary risks.

Clinical Trial Conditions for Nalidixic Acid

Condition Name

Condition Name for Nalidixic Acid
Intervention	Trials
Atrial Fibrillation	1
Cholera	1
H. Pylori Associated Phlegmonous Gastritis	1
H. Pylori Infection	1

Condition MeSH

Condition MeSH for Nalidixic Acid
Intervention	Trials
Neoplasms	1
Cholera	1
Gastrointestinal Diseases	1
Gastritis	1

Clinical Trial Locations for Nalidixic Acid

Trials by Country

Trials by Country for Nalidixic Acid
Location	Trials
United States	6
Bangladesh	1
Greece	1
Brazil	1

Trials by US State

Trials by US State for Nalidixic Acid
Location	Trials
New York	2
North Carolina	1
Maryland	1
Florida	1
Texas	1

Clinical Trial Progress for Nalidixic Acid

Clinical Trial Phase

Clinical Trial Phase for Nalidixic Acid
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Nalidixic Acid
Clinical Trial Phase	Trials
Completed	3
Recruiting	2
Unknown status	1

Clinical Trial Sponsors for Nalidixic Acid

Sponsor Name

Sponsor Name for Nalidixic Acid
Sponsor	Trials
International Centre for Diarrhoeal Disease Research, Bangladesh	1
The University of Texas Health Science Center, Houston	1
Sidney Kimmel Comprehensive Cancer Center	1

Sponsor Type

Sponsor Type for Nalidixic Acid
Sponsor	Trials
Other	9

Nalidixic Acid: Clinical Trials, Market Analysis, and Projections

Introduction to Nalidixic Acid

Nalidixic acid is a quinolone antibiotic that has been widely used for the treatment of urinary tract infections (UTIs) since its global approval in 1964. Developed by Sanofi, this small molecule drug targets bacterial Top II, an enzyme crucial for bacterial DNA replication and repair[3].

Clinical Trials and Approval

Nalidixic acid has successfully completed the highest phase of clinical trials and has been approved globally for the treatment of UTIs. The drug was first approved in the United States in March 1964 and has since been recognized for its efficacy in combating bacterial infections in the urinary system[3].

Mechanism of Action

Nalidixic acid works by inhibiting the activity of bacterial Top II, thereby disrupting the growth and survival of bacteria. Its active metabolite, hydroxynalidixic acid, binds strongly to DNA, interfering with RNA and protein synthesis. This mechanism makes it effective against a range of gram-negative bacteria, including Escherichia coli, Proteus mirabilis, and Morganella morganii[4].

Pharmacokinetics

Absorption and Metabolism

Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract, with a bioavailability of approximately 96%. It is partially metabolized in the liver to its active metabolite, hydroxynalidixic acid, which represents about 30% of the biologically active drug in the blood and up to 85% in the urine. The drug and its metabolites are rapidly excreted through the kidneys[1][4].

Protein Binding and Elimination

Nalidixic acid is 93% bound to protein in the blood, while its active metabolite is 63% bound. The half-life of nalidixic acid is about 90 minutes, with peak serum levels occurring one to two hours after administration. Peak urine levels are reached three to four hours after administration, with a half-life of about six hours[1].

Market Analysis

Global Market Size and Growth

The global market for nalidixic acid has shown steady growth over the years. As of 2021, the market size was valued at several million dollars, with a projected compound annual growth rate (CAGR) that is expected to drive the market to reach a significant value by 2028[2][5].

Market Segmentation

The nalidixic acid market is segmented by company, country, and application/type. Key players in the market include major pharmaceutical companies as well as smaller entities. The report provides detailed company profiles, including sales, revenue, price, gross margin, and market share. The market is also analyzed by region, with key countries such as the United States, China, Japan, India, and several European nations being significant contributors[2][5].

Competitive Landscape

The competitive landscape of the nalidixic acid market is characterized by a mix of global key players and smaller competitors. The report includes SWOT analyses, sales data, and market shares for each competitor. This analysis helps in understanding the market dynamics and growth opportunities for new and existing players[2][5].

Market Projections

Future Trends and Growth Opportunities

The market for nalidixic acid is expected to continue growing, driven by increasing demand for effective treatments for UTIs. The report estimates market development trends from 2022 to 2028, including analysis of upstream raw materials, downstream demand, and current market dynamics. It also provides proposals for new projects in the nalidixic acid industry, evaluating their feasibility based on market conditions[2][5].

Regional Analysis

The market is analyzed at the regional level, including North America, South America, Asia & Pacific, Europe, and the Middle East and Africa. The report highlights the demand and supply forces influencing the growth of the market in each region, providing valuable insights for companies and individuals interested in the industry[2][5].

Safety and Efficacy Considerations

Susceptibility and Resistance

Nalidixic acid is effective against a range of gram-negative bacteria, but it is generally ineffective against Pseudomonas species. The minimum inhibitory concentration (MIC) is used to determine susceptibility, with MIC values of ≤16 mcg/mL indicating susceptibility and ≥32 mcg/mL indicating resistance[1].

Side Effects and Contraindications

Nalidixic acid can cause several side effects, including QTc interval prolongation, peripheral neuropathies, and cartilage erosions in weight-bearing joints. It should be avoided in patients receiving certain antiarrhythmic agents and used with caution in those receiving drugs that affect the QTc interval. The drug is contraindicated during lactation and should be used with caution during pregnancy due to its teratogenic and embryocidal effects in animal studies[1].

Conclusion

Nalidixic acid remains a significant therapeutic option for the treatment of urinary tract infections, with a long history of global approval and clinical use. Its mechanism of action, targeting bacterial Top II, makes it effective against a range of bacterial pathogens. The market for nalidixic acid is projected to grow, driven by increasing demand for effective UTI treatments, although it faces competition from newer antibiotics and must be used cautiously due to potential side effects.

Key Takeaways

• Clinical Approval: Nalidixic acid has been approved globally since 1964 for treating UTIs.
• Mechanism of Action: It inhibits bacterial Top II, disrupting bacterial DNA replication and repair.
• Pharmacokinetics: Rapidly absorbed, partially metabolized, and excreted through the kidneys.
• Market Growth: Projected to grow with a significant CAGR from 2022 to 2028.
• Safety Considerations: Potential side effects include QTc interval prolongation and peripheral neuropathies.

FAQs

Q: What is the primary use of nalidixic acid?

A: Nalidixic acid is primarily used for the treatment of urinary tract infections (UTIs).

Q: How does nalidixic acid work?

A: Nalidixic acid works by inhibiting the activity of bacterial Top II, disrupting bacterial DNA replication and repair.

Q: What are the potential side effects of nalidixic acid?

A: Potential side effects include QTc interval prolongation, peripheral neuropathies, and cartilage erosions in weight-bearing joints.

Q: Is nalidixic acid safe during pregnancy and lactation?

A: Nalidixic acid should be used with caution during pregnancy due to its teratogenic and embryocidal effects in animal studies. It is contraindicated during lactation.

Q: How is the susceptibility of bacteria to nalidixic acid determined?

A: Susceptibility is determined by the minimum inhibitory concentration (MIC), with MIC values of ≤16 mcg/mL indicating susceptibility and ≥32 mcg/mL indicating resistance.

Sources

1. Drugs.com: NegGram: Package Insert / Prescribing Information.
2. 24MarketReports: Global Nalidixic Acid Market | Size, share, status 2022 forecast to 2030.
3. Patsnap Synapse: Nalidixic Acid Unveiled: A Detailed Overview of its Revolutionary R&D Breakthroughs.
4. DrugBank: Nalidixic acid: Uses, Interactions, Mechanism of Action.
5. 24MarketReports: Nalidixic Acid Market | Size, share, status 2022 forecast to 2030.