Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study

Abstract

BackgroundInosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age.MethodsA total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations.ResultsThe difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806–1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m2). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m2) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported.ConclusionsThe study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses.Trial registrationEWO-ISO-2014/1, EudraCT 2014-001863-11; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1965-5) contains supplementary material, which is available to authorized users.

Застосування Інозину Пранобексу При Гострих Респіраторних Вірусних Інфекціях У Дітей

“…Установлено, что инозин пранобекс активирует моноциты и макрофаги, индуцируя хемотаксис, продукцию цитокинов [27,39]. После приема первой дозы инозина пранобекса у 75 % пациентов наблюдается быстрое увеличение представительства мононуклеарных клеток, и этот индуцированный ответ мононуклеарных клеток сопряжен с более быстрым процессом выздоровления и благоприятным течением острых респираторных инфекций [20].…”

“…Инозин пранобекс индуцирует цитотоксичность CD8 + Т-лимфоцитов [20], дифференцировку В-клеток в плазматические клетки и способствует продукции иммуноглобулинов, в том числе и специфических антител, направленных против антигенов возбудителей инфекционных заболеваний. Повышение активности синтеза специфических антител предопределяет усиление клиренса патогенных вирусов и бактерий [27].…”

4-Aminobenzoic Acid Derivatives: Converting Folate Precursor to Antimicrobial and Cytotoxic Agents

“…Hz, 1.7 Hz, H4 ), 6.85-6.79 (2H, m, NH, H3 ), 6.73 (1H, td, J = 7.4 Hz, 1.1 Hz, H5 ), 6.60-6.56 (2H, m, H3, H5), 4.24 (2H, d, J = 5.8 Hz, CH 2 ). 13 The microdilution broth method was performed according to EUCAST (The European Committee on Antimicrobial Susceptibility Testing) instructions with slight modifications [33]. Briefly, the cultivation was done in Cation-adjusted Mueller-Hinton broth (CAMHB, M-H 2 Broth, Sigma-Aldrich) at 35 ± 2 • C. Tested compounds were dissolved in DMSO (Sigma-Aldrich, St. Louis, MO, USA) to produce stock solutions.…”

“…A natural metabolite of PABA, 4-acetamidobenzoic acid (acedoben, Figure 1, I), is also able to interfere with the function of dihydropteroate synthase [12]. This molecule is one of the components of immunomodulating and antiviral drug inosine pranobex (Isoprinosine; Figure 1, II) [13]. Antitubercular drug 4-aminosalicylic acid (Figure 1, III) is utilized by dihydropteroate synthase instead of PABA and incorporated into the folate pathway to generate a hydroxyl dihydrofolate antimetabolite, which interferes with dihydrofolate reductase activity leading to the disruption of the biosynthesis of purines and thymidylate [11,14].…”

“…) 13. C-NMR (126 MHz, DMSO-d 6 ): δ 166.95, 165.17, 156.69, 150.75, 133.77, 132.22, 130.92, 129.52, 121.87, 120.56, 120.19, 119.85.…”