CLINICAL TRIALS PROFILE FOR PIVMECILLINAM HYDROCHLORIDE

505(b)(2) Clinical Trials for Pivmecillinam Hydrochloride

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
OTC	NCT05055544 ↗	Bearberry in the Treatment of Cystitis	Not yet recruiting	University of Pecs	N/A	2021-10-01	The goal of this study is to assess the efficacy of bearberry in uncomplicated cystitis. Uncomplicated cystitis is a disease related to the infection of the urinary bladder. Typical symptoms are dysuria, urinary urgency, and frequent voiding of small volumes. Urinary tract infections are frequent in women, usually treated with antibiotics, since the disease is usually caused by bacteria. Fosfomycin is a frequently used antibiotic for the treatment of uncomplicated cystitis. This medicine is typically prescribed by MDs. However, since uncomplicated cystitis is quite frequent, not all patients visit the doctor when experiencing the symptoms of this disease. The use of over-the-counter products (medicines and food supplements) to alleviate the symptoms is common. One of the most frequently used medicinal plants for this purpose is bearberry. Bearberry is a medicinal plant traditionally used for the treatment of cystitis. Its use is accepted by the European Medicine Agency as traditional herbal medicinal product for relief of symptoms of mild recurrent lower urinary tract infections such as burning sensation during urination and/or frequent urination in women. Although the experience gained during the traditional use and the laboratory experiments support the supposed beneficial effect of bearberry, its clinical efficacy has not been confirmed in well-designed clinical trials in comparison with standard antibiotic therapy. In this study, the efficacy of bearberry will be assessed in comparison with fosfomycin. Premenopausal women experiencing the symptoms of uncomplicated cystitis will be randomly divided into two groups. Since it will be a double-blind trial, neither the participants nor the experimenters will know who is receiving a particular treatment. In group A, patients will receive a single dose of fosfomycin powder dissolved in water and 2 placebo tablets three times a day for 7 days. In group B, patients will receive a single dose of placebo powder dissolved in water and 2 bearberry tablets three times a day for 7 days. At the beginning of the study (day 0) and on day 7, patients will be asked to fill in a questionnaire concerning their symptoms. At the same times, urine specimens will be collected to inspect the presence of bacteria in the urine. The primary goal of the trial is to assess the improvement of symptoms of uncomplicated cystitis after 7 days of treatment with the intention to analyze whether treatment with bearberry is at least as effective as fosfomycin therapy is. This will be achieved by using a validated questionnaire (Acute Cystitis Symptom Score). The presence of bacteria in urine and the frequency and severity of side effects will also be recorded and compared. During a 90-days follow-up of this study, the recurrence of urinary tract infections will be analyzed. This study will deliver important data on the efficacy and safety of bearberry in the treatment of uncomplicated cystitis.

All Clinical Trials for Pivmecillinam Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03228108 ↗	Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.	Active, not recruiting	ZonMw: The Netherlands Organisation for Health Research and Development	Phase 4	2018-04-03	This study aims to assess the effectiveness and cost-effectiveness of rectal swab culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral ciprofloxacin (control group), while the other half will receive rectal culture-guided oral antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis, comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative oral antibiotic based on the culture results will be prescribed (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin). The investigators hypothesise that the targeted prophylaxis group (intervention group) will have a lower rate of post-biopsy infectious complications compared to the control group.
NCT03228108 ↗	Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.	Active, not recruiting	Radboud University	Phase 4	2018-04-03	This study aims to assess the effectiveness and cost-effectiveness of rectal swab culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral ciprofloxacin (control group), while the other half will receive rectal culture-guided oral antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis, comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative oral antibiotic based on the culture results will be prescribed (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin). The investigators hypothesise that the targeted prophylaxis group (intervention group) will have a lower rate of post-biopsy infectious complications compared to the control group.
NCT03282006 ↗	Treating Pyelonephritis an Urosepsis With Pivmecillinam	Completed	University of Oslo	Phase 4	2017-09-29	Febrile urinary tract infections and urosepsis are common and potentially serious infections that require effective antimicrobial treatment. The duration of parenteral treatment depends on oral alternatives. These alternatives are few and due to antimicrobial resistance, quinolones are "standard of care". The increased use of quinolones is concerning because of its negative ecological aspects and it is confirmed an increasing incidence of resistant E.coli to quinolones in Norwegian isolates. Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for treating febrile urinary tract infections is insufficient. This trial will investigate the efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by E.coli. The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given after 2-3 days with empirical i.v. antibiotics.
NCT03282006 ↗	Treating Pyelonephritis an Urosepsis With Pivmecillinam	Completed	Sykehuset i Vestfold HF	Phase 4	2017-09-29	Febrile urinary tract infections and urosepsis are common and potentially serious infections that require effective antimicrobial treatment. The duration of parenteral treatment depends on oral alternatives. These alternatives are few and due to antimicrobial resistance, quinolones are "standard of care". The increased use of quinolones is concerning because of its negative ecological aspects and it is confirmed an increasing incidence of resistant E.coli to quinolones in Norwegian isolates. Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for treating febrile urinary tract infections is insufficient. This trial will investigate the efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by E.coli. The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given after 2-3 days with empirical i.v. antibiotics.
NCT04959331 ↗	Clinical Effectiveness and Bacteriological Eradication of 4 Short-course Antibiotics for Uncomplicated UTIs in Women.	Not yet recruiting	Balearic Islands Health Service (Ibsalut)	Phase 4	2021-11-02	Randomized clinical trial in which women aged 18 or older and with symptoms of uncomplicated lower urinary tract infection and a positive urine dipstick analysis will be randomized to one of the following four groups: 2-day 3 g fosfomycin o.d., 3-day pivmecillinam 400 mg. t.i.d, 5-day nitrofurantoin 100 mg t.i.d. or a single dose of 3 g of fosfomycin. Sample: 1,000 patients. Two co-primary endpoints are considered: clinical effectiveness at day 7 and bacteriological eradication at day 14. Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed.
NCT04959331 ↗	Clinical Effectiveness and Bacteriological Eradication of 4 Short-course Antibiotics for Uncomplicated UTIs in Women.	Not yet recruiting	Gerencia de Atención Primaria, Madrid	Phase 4	2021-11-02	Randomized clinical trial in which women aged 18 or older and with symptoms of uncomplicated lower urinary tract infection and a positive urine dipstick analysis will be randomized to one of the following four groups: 2-day 3 g fosfomycin o.d., 3-day pivmecillinam 400 mg. t.i.d, 5-day nitrofurantoin 100 mg t.i.d. or a single dose of 3 g of fosfomycin. Sample: 1,000 patients. Two co-primary endpoints are considered: clinical effectiveness at day 7 and bacteriological eradication at day 14. Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed.

Clinical Trial Conditions for Pivmecillinam Hydrochloride

Condition Name

Condition Name for Pivmecillinam Hydrochloride
Intervention	Trials
Urinary Tract Infections	3
Complication	1
Cystitis	1
Infection	1

Condition MeSH

Condition MeSH for Pivmecillinam Hydrochloride
Intervention	Trials
Urinary Tract Infections	4
Infections	3
Communicable Diseases	2
Cystitis	1

Clinical Trial Locations for Pivmecillinam Hydrochloride

Trials by Country

Trials by Country for Pivmecillinam Hydrochloride
Location	Trials
China	9
Spain	5
Norway	1
Netherlands	1
Hungary	1

Clinical Trial Progress for Pivmecillinam Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Pivmecillinam Hydrochloride
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	2
N/A	1

Clinical Trial Status

Clinical Trial Status for Pivmecillinam Hydrochloride
Clinical Trial Phase	Trials
Not yet recruiting	4
Completed	1
Active, not recruiting	1

Clinical Trial Sponsors for Pivmecillinam Hydrochloride

Sponsor Name

Sponsor Name for Pivmecillinam Hydrochloride
Sponsor	Trials
Sykehuset i Vestfold HF	1
Balearic Islands Health Service (Ibsalut)	1
Gerencia de Atención Primaria, Madrid	1

Sponsor Type

Sponsor Type for Pivmecillinam Hydrochloride
Sponsor	Trials
Other	11

Pivmecillinam Hydrochloride: A New Frontier in Treating Uncomplicated Urinary Tract Infections

Introduction

Pivmecillinam hydrochloride, a member of the aminopenicillin class of beta-lactam antibiotics, has recently gained significant attention with its approval by the US Food and Drug Administration (FDA) for the treatment of uncomplicated urinary tract infections (UTIs) in adult female patients. This article delves into the clinical trials that led to its approval, its market analysis, and projections for its future impact.

Clinical Trials Overview

The FDA approval of pivmecillinam hydrochloride was based on data from three randomized controlled trials that compared the efficacy of pivmecillinam against placebo, another antibiotic, and an anti-inflammatory drug (ibuprofen)[2][4].

Trial Design and Participants

These trials enrolled adult female patients with uncomplicated UTIs caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. The primary endpoint was a composite response rate, which included clinical cure (resolution of symptoms) and microbiological response (reduction in bacteria culture)[4].

Efficacy Against Placebo

In the trial comparing pivmecillinam to placebo, 62% of the 137 patients who received pivmecillinam achieved a composite response, whereas only 10% of the 134 patients who received placebo achieved the same outcome[2][4].

Efficacy Against Another Antibiotic

When compared to another oral antibacterial drug, 72% of the 127 patients who received pivmecillinam achieved a composite response, which was similar to the 76% of the 132 patients who received the comparator drug[2][4].

Efficacy Against Ibuprofen

In the trial comparing pivmecillinam to ibuprofen, 66% of the 105 patients who received pivmecillinam achieved a composite response, significantly higher than the 22% of the 119 patients who took ibuprofen[2][4].

Safety Profile

Pivmecillinam hydrochloride was generally well tolerated in these trials. The most common adverse reactions reported were nausea and diarrhea, indicating a favorable safety profile[4].

Market Analysis

Current Market Need

Uncomplicated UTIs are a common condition, particularly among women, and are one of the most frequent reasons for antibiotic use. The current market is in dire need of new, effective, and safe antibiotic options due to the increasing prevalence of antibiotic-resistant bacteria[4].

Competitive Landscape

The approval of pivmecillinam hydrochloride marks a significant milestone, especially given the efforts of the AMR Action Fund, which aims to bring new antibiotics to market to combat antimicrobial resistance. Pivmecillinam is the first antibiotic in the AMR Action Fund's portfolio to receive regulatory approval, highlighting its potential to fill a critical gap in the market[2].

Market Potential

Given its efficacy and safety profile, pivmecillinam hydrochloride is poised to become a valuable treatment option for uncomplicated UTIs. Its approval is expected to benefit patients by providing a new and urgently needed treatment, thereby reducing the reliance on older antibiotics and mitigating the risk of antibiotic resistance.

Projections and Future Impact

Clinical Utility

Pivmecillinam hydrochloride's excellent clinical efficacy against uncomplicated UTIs, particularly those caused by Gram-negative bacteria, makes it a timely addition to the clinical formulary. Its use is expected to be particularly beneficial in regions where ESBL-producing organisms are prevalent, given its activity against these resistant strains[5].

Resistance Profile

Despite its widespread use in Nordic countries, pivmecillinam has shown a low rate of resistance. A large Portuguese surveillance study calculated a 16% resistance rate among all urinary pathogens, which is relatively low compared to other antibiotics[5].

Synergistic Potential

There is emerging evidence of pivmecillinam's synergistic potential with β-lactamase inhibitors, which could further enhance its effectiveness against resistant bacteria. This synergy could be a key factor in its future clinical use and development[5].

Impact on Public Health

The introduction of pivmecillinam hydrochloride is expected to have a positive impact on public health by providing a new treatment option that is less likely to select for resistant bacteria. This reduces the risk of complications such as vaginal candidiasis and Clostridium difficile infections, which are often associated with broader-spectrum antibiotics[5].

Expert Insights

Henry Skinner, PhD, CEO of AMR Action Fund: "Bringing pivmecillinam to the U.S. has the potential to benefit patients suffering from these harmful infections by giving clinicians a new, urgently needed treatment option for uncomplicated UTIs."[2]

Peter Kim, MD, MS, Director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research: "Uncomplicated UTIs are a very common condition impacting women and one of the most frequent reasons for antibiotic use. The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Pivya will provide an additional treatment option for uncomplicated UTIs."[4]

Key Takeaways

• FDA Approval: Pivmecillinam hydrochloride has been approved by the FDA for treating uncomplicated UTIs in adult female patients.
• Clinical Efficacy: It has shown superior efficacy compared to placebo and ibuprofen and similar efficacy to another antibiotic in clinical trials.
• Safety Profile: The drug is generally well tolerated with common adverse reactions including nausea and diarrhea.
• Market Need: It fills a critical gap in the market for new, effective antibiotics to combat antimicrobial resistance.
• Future Impact: Expected to benefit patients by providing a new treatment option and reducing the risk of antibiotic resistance.

FAQs

What is pivmecillinam hydrochloride used for?

Pivmecillinam hydrochloride is used for the treatment of uncomplicated urinary tract infections (UTIs) in adult female patients caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus[4].

How effective is pivmecillinam hydrochloride compared to other treatments?

In clinical trials, pivmecillinam hydrochloride showed a composite response rate of 62% against placebo, 72% against another antibiotic, and 66% against ibuprofen, indicating its superior efficacy[2][4].

What are the common adverse reactions associated with pivmecillinam hydrochloride?

The most common adverse reactions reported are nausea and diarrhea[4].

How does pivmecillinam hydrochloride impact antibiotic resistance?

Pivmecillinam hydrochloride has a low rate of resistance and minimal effect on the intestinal and vaginal flora, reducing the selection of resistant bacteria and associated complications[5].

Is pivmecillinam hydrochloride widely available?

Pivmecillinam hydrochloride has been approved by the FDA and is expected to become widely available as a treatment option for uncomplicated UTIs in the U.S.[2].

Sources

1. Creighton University - June 2024 Newsletter - Creighton University
2. CIDRAP - FDA approves new treatment for uncomplicated urinary tract infections
3. Health Canada - Details for: SELEXID - Drug and Health Products Portal
4. Urology Times - FDA approves pivmecillinam tablets for uncomplicated UTIs
5. Journal of Antimicrobial Chemotherapy - Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria