A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59® -adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects

PubMed ID: 23362618Background. Effective planning and preparedness against a possible future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adjuvanted vaccine formulations of relatively lower antigen content. Aim. This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 mg) A/H5N1 pre-pandemic vaccine compared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. Methods. A total of 722 subjects were randomized in equal numbers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the administration of each vaccine dose by hemagglutination inhibition (HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. Results. The low-dose vaccine was demonstrated to be non-inferior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two criteria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. Conclusion. These data demonstrate that a low antigen dose in combination with MF59® adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects

A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59®-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects

ackground. Effective planning and preparedness against a possi- ble future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adju- vanted vaccine formulations of relatively lower antigen content. Aim. This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 mg) A/H5N1 pre-pandemic vaccine com- pared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. Methods. A total of 722 subjects were randomized in equal num- bers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the admin- istration of each vaccine dose by hemagglutination inhibition HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. Results. The low-dose vaccine was demonstrated to be non-infe- rior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two crite- ria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. Conclusion. These data demonstrate that a low antigen dose in combination with MF59® adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects

Real-life safety and efficacy of vildagliptin as add-on to metformin in patients with type 2 diabetes in Turkey - GALATA study

PubMed ID: 25697921Objective: To evaluate tolerability/safety and the efficacy of the combination of vildagliptin plus metformin in a real-life population of patients with type 2 diabetes mellitus (T2DM). Research design and methods: This multicenter, single-arm, 6 month, observational, prospective cohort study was conducted at 39 centers across Turkey. T2DM patients on vildagliptin and metformin for ?4 weeks were enrolled regardless of their previous antidiabetic therapy. Main outcome measures: Efficacy was evaluated by measuring hemoglobin A1c (HbA1c) levels. Tolerability/safety parameters evaluated included hypoglycemic events, gastrointestinal events, peripheral edema and weight gain. Results: This study enrolled 665 patients with a mean±standard deviation (SD) age of 55.1±10.2 years and female predominance (n=394, 59.2%). Safety was assessed in all enrolled patients. Hypoglycemia was reported in 10 (1.5%) patients (95% confidence interval = 0.8-2.7%). Efficacy was assessed in 289 (43.5%) patients treated for 6±1 months; these patients showed a mean decrease in HbA1c of 0.8% from baseline value of 7.8% (p65 years) and body mass index (<30 vs. ?30 kg/m2) (p<0.001 each). In total, 136 adverse events (AEs) were observed in 71 (10.7%) patients; 10 (1.5%) patients experienced hypoglycemia and gastrointestinal AEs were most commonly reported (n=29, 4.4%). Conclusions: In a 'real-life' setting, the vildagliptin and metformin combination was associated with significant improvements in reaching target HbA1c levels, even in elderly and obese patients with T2DM. Moreover, vildagliptin and metformin demonstrated a good overall tolerability/safety profile. © 2015 All rights reserved: reproduction in whole or part not permitted.Novartis Pharmaceuticals CanadaThe study was funded by Novartis Pharmaceuticals Turkey. -- The authors thank Cagla Ayhan MD and Prof. Sule Oktay MD PhD from Kappa Consultancy Training Research Ltd, Istanbul, who provided editorial support, and Mehmet Berktas MD MICR from Kappa Consultancy Training Research Ltd, Istanbul, who performed statistical analysis funded by Novartis Pharmaceuticals Turkey. -

Real-life safety and efficacy of vildagliptin as add-on to metformin in patients with type 2 diabetes in Turkey - GALATA study

Objective: To evaluate tolerability/safety and the efficacy of the combination of vildagliptin plus metformin in a real-life population of patients with type 2 diabetes mellitus (T2DM). Research design and methods: This multicenter, single-arm, 6 month, observational, prospective cohort study was conducted at 39 centers across Turkey. T2DM patients on vildagliptin and metformin for ≤4 weeks were enrolled regardless of their previous antidiabetic therapy. Main outcome measures: Efficacy was evaluated by measuring hemoglobin A1c (HbA1c) levels. Tolerability/safety parameters evaluated included hypoglycemic events, gastrointestinal events, peripheral edema and weight gain. Results: This study enrolled 665 patients with a mean±standard deviation (SD) age of 55.1±10.2 years and female predominance (n=394, 59.2%). Safety was assessed in all enrolled patients. Hypoglycemia was reported in 10 (1.5%) patients (95% confidence interval = 0.8-2.7%). Efficacy was assessed in 289 (43.5%) patients treated for 6±1 months; these patients showed a mean decrease in HbA1c of 0.8% from baseline value of 7.8% (p65 years) and body mass index (<30 vs. ≥30 kg/m2) (p<0.001 each). In total, 136 adverse events (AEs) were observed in 71 (10.7%) patients; 10 (1.5%) patients experienced hypoglycemia and gastrointestinal AEs were most commonly reported (n=29, 4.4%). Conclusions: In a 'real-life' setting, the vildagliptin and metformin combination was associated with significant improvements in reaching target HbA1c levels, even in elderly and obese patients with T2DM. Moreover, vildagliptin and metformin demonstrated a good overall tolerability/safety profile. © 2015 All rights reserved: reproduction in whole or part not permitted