The IND clearance will initiate a phase 2 registrational study to investigate the safety and efficacy of NRX-101 in patients with complicated UTIs.
The FDA has accepted an Investigational New Drug (IND) application for NRX-101, a combination of D-cycloserine (DCS) and lurasidone for the potential treatment of patients with complicated urinary tract infections (UTIs), announced NRx Pharmaceuticals, the developer of the compound, in a news release.1
The IND clearance will initiate a phase 2 registrational study (NCT06128213) to investigate the safety and efficacy of NRX-101 in patients with complicated UTIs, including pyelonephritits.2
"Complicated urinary tract Infections afflict approximately 3 million Americans each year, and pathogens have become increasingly resistant to commonly used antibiotics. New treatment options are urgently needed," said Jonathan C. Javitt, MD, MPH, in the news release.1 Javitt is the founder and chief scientist of NRx Pharmaceuticals.
Javitt continued, "The D-cycloserine (DCS) component of NRX-101 is well known as an antibiotic and is excreted unmetabolized in the urine. However, the NMDA-antagonist effects of DCS led to its disuse in the United States, while it has remained a widely used anti-tuberculosis agent by the World Health Organization. NRx's patented discovery that combining DCS with small amounts of lurasidone counters the CNS side effects potentially and renders NRX-101 an important, patented antibiotic, just at a time when Americans are increasingly facing intravenous antibiotic therapy and even hospitalization and death from pathogens that were readily controlled a generation ago. This mission is personal to me, in that I have lost 2 close friends, one the father of a founding investor, to sepsis from urinary infections that were readily controlled a generation ago."
In total, the open-label study of NRX-101 is seeking to enroll 13 adult patients who will undergo a fixed dose combination of 487.5 mg DCS and 16.5 mg lurasidone HCI orally twice daily for 10 days. Patients will be seen across approximately 6 visits to assess for any signs or symptoms of UTI or any adverse events. They will also answer a 10-item questionnaire, have their vital signs and weight assessed, and undergo a urine test and blood draw during these visits.
The primary end point of the study is the number of patients with a microbiologic response at the test of cure visit, assessed on day 14.
Exclusion criteria includes receipt of an effective antibacterial drug therapy for complicated UTIs for more than 48 hours during the 72 hours prior to screening, a concomitant infection that requires a non-study systemic antibacterial therapy, and intractable UTI at baseline that may require more than 14 days of study drug therapy.
The study start is anticipated for early next year.
In preclinical studies, NRX-101 demonstrated potent antibacterial activity against antibiotic-resistant pathogens in culture medium and an artificial urine model. The pathogens were reference strains of urinary tract pathogens known to cause complicated UTIs.3
NRX-101 is also currently being assessed for the treatment of suicidal treatment-resistant bipolar depression and chronic pain. According to the news release, NRx Pharmaceuticals is awaiting a response on a Qualified Infectious Disease Product designation for NRX-101, which they expect to receive next month.
Principal investigator of the current study, Michael J. Manyak, MD, concluded in the news release, "At a time when routine use of standard antibiotics demonstrates increasing resistance and failure to control urinary tract infections, I believe it is vital to advance safe, oral antibiotics for complicated UTI that have the potential to avoid the need for intravenous therapy, to keep patients out of the hospital, and to save lives. I look forward to learning whether the efficacy we demonstrated for NRX-101 in the laboratory against some of the most resistant bacteria can be replicated in patients."1
1. NRx Pharmaceuticals announces FDA clearance of its Investigational New Drug (IND) application for NRX-101 in the treatment of complicated urinary tract infections. News release. NRX Pharamceuticals Inc. Published online and accessed December 18, 2023. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-announces-fda-clearance-of-its-investigational-new-drug-ind-application-for-nrx-101-in-the-treatment-of-complicated-urinary-tract-infections-302017523.html
2. NRX-101 for complicated urinary tract infection (UTI) including pyelonephritis. ClinicalTrials.gov. Last updated November 13, 2023. Accessed December 18, 2023. https://clinicaltrials.gov/study/NCT06128213
3. NRx Pharmaceuticals announces potent antibacterial activity of NRX-101 against common, antibiotic resistant urinary pathogens. News release. NRx Pharmaceuticals. September 6, 2023. Accessed December 18, 2023. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-announces-potent-antibacterial-activity-of-nrx-101-against-common-antibiotic-resistant-urinary-pathogens-301919431.html