The efficacy and safety of tazobactam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection.

We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a ß-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. This study design was a nonrandomized, multicenter, open-label trial, and the treatment period was 7 days. Of 115 patients enrolled in this study, 114 received tazobactam/ceftolozane, and 90 were included in the efficacy analyses. Ninety-nine isolates (bacterial count ≥105 CFU/mL) were identified by urine culture. The main baseline uropathogens were Escherichia coli (80 isolates), Klebsiella pneumoniae (8 isolates), and Proteus mirabilis (3 isolates). Of these, 13 isolates were ESBL-producers. The favorable per-patient microbiological response rate at 7 days after the final administration of tazobactam/ceftolozane was 80.7% (71/88). The response rate in uncomplicated pyelonephritis was 90.0% (36/40), complicated pyelonephritis 63.6% (14/22), and complicated cystitis 80.8% (21/26). The favorable clinical response rate was 96.6% (86/89), and composite response rate (based on microbiological and clinical response) was 80.7% (71/88). The eradication rate by uropathogen was 83.5% (66/79) in E. coli, 42.9% (3/7) in K. pneumoniae, and 100% (3/3) in P. mirabilis. The incidence of drug-related adverse events was 17.5% (20/114 patients). The most common drug-related adverse events were diarrhea and alanine aminotransferase increased in 5.3% (6/114 patients each). Drug-related serious adverse events and deaths were not observed. These results support the safety and efficacy of tazobactam/ceftolozane and suggest it will be a useful treatment for uncomplicated pyelonephritis and complicated urinary tract infection.

Efficacy, safety, and immunogenicity of a quadrivalent HPV vaccine in Japanese men: A randomized, Phase 3, placebo-controlled study.

BACKGROUND: The quadrivalent (q) human papillomavirus (HPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, and 18. We report efficacy, immunogenicity, and safety of qHPV vaccine in a Phase 3 study in Japanese men. METHODS: In this randomized, double-blind trial (NCT01862874), Japanese men (aged 16-26 years) were randomized in a 1:1 ratio to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). The primary efficacy endpoint was the combined incidence of HPV6/11/16/18-related persistent anogenital infection (detected at ≥2 consecutive visits ≥6 months apart), assessed in the per-protocol population of men who received all three vaccinations, and were seronegative at Day 1 and PCR negative from Day 1 to Month 7 to the relevant HPV type. Results are from the interim and final analyses. RESULTS: In total, 1124 participants were randomized. The vaccine demonstrated 83.3% (95% confidence interval: 24.9, 98.2; p = 0.007) and 85.9% (95% confidence interval: 52.7, 97.3; p < 0.001) efficacy against HPV6/11/16/18-related persistent infection in the interim and final analyses, respectively. Two cases of HPV6/11/16/18-related external genital lesions (condyloma and PIN 1) were observed in the placebo group and none in the qHPV vaccine group at study end. At Month 7, >97% of participants who received qHPV vaccine seroconverted to each of the vaccine HPV types. Most participants remained seropositive at Month 36, although the seropositivity rate declined between Months 7 and 36. Vaccination-related adverse events were reported in 60.8% and 56.5% of participants in the qHPV vaccine and placebo groups, respectively; most commonly mild to moderate injection-site pain, erythema, and swelling. Injection-site pain and swelling were more common with qHPV vaccine than placebo (each p < 0.05). CONCLUSIONS: Results suggest qHPV vaccine is efficacious against HPV6/11/16/18-related persistent infections, immunogenic, and well-tolerated in Japanese men. Clinical trial registration identifier: NCT01862874.

Safety and Immunogenicity of the Quadrivalent HPV Vaccine in Japanese Boys: a Phase 3, Open-Label Study.

Human papillomavirus (HPV)-associated disease is common among men with HPV infection. A quadrivalent HPV (qHPV) vaccine has demonstrated 85.9% efficacy against HPV6/11/16/18-related, persistent (≥ 6 month) infection in a study of Japanese men aged 16-26 years old. Here, we report the results of an open-label study of the immunogenicity and tolerability of the qHPV vaccine (NCT02576054), conducted to bridge findings from Japanese men to Japanese boys aged 9-15 years old. A total of 100 boys completed a three-vaccination regimen (Day 1, and Months 2 and 6), and 99 boys were included in the primary analysis population. The rate of seroconversion at one month after vaccine Dose 3 (Month 7) was high for each type of HPV (anti-HPV6/11/16/18 seroconversion rates [95% CI]: 94.9% [85.5%, 98.3%], 99.0% [94.4%, 100.0%], 99.0% [94.5%, 100.0%], and 99.0% [94.4%, 100.0%], respectively). Moreover, anti-HPV6/11/16/18 geometric mean titers were 482.9 mMU/mL, 1052.8 mMU/mL, 3878.3 mMU/mL, and 1114.5 mMU/mL, respectively. Immune responses to the qHPV vaccine were non-inferior among Japanese boys included in the current study and compared with young Japanese men from a separate study. Injection-site reactions were the most common adverse events, and administration of the vaccine was well tolerated in Japanese boys.

Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.

Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.