Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate.

BACKGROUND: An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals. METHODS: Safety findings are presented herein from an integrated analysis of data for healthy 4-60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender. RESULTS: The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1-3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively). CONCLUSIONS: No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4-60 years.

Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO).

BACKGROUND: This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD). METHODS: The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD). The primary efficacy outcome was percentage change in the initial claudication distance (ICD) by week 12. Secondary outcomes included percent and absolute changes in ICD, absolute claudication distance (ACD) and changes in Quality of Life (QoL) assessed by the SF-36 Mental Health Score. RESULTS: The increase in ICD after 12 weeks of Actovegin treatment was 29.19% (LS mean [Actovegin vs. placebo]; 95% CI: 9.35-49.02; P=0.0041). The percentage increase in ICD at 24 weeks was 35.51% (LS mean; 95% CI: 10.96-60.05; P=0.0047), which correspond to an increase in absolute ICD of 41.22 m (LS mean; 95% CI: 16.77-65.66; P=0.0010). The percentage increase in ACD after 24 weeks was 36.47% compared with the baseline (LS mean; 95% CI: 10.07-62.88; P=0.0069), which corresponded to an absolute increase in ACD of 50.92 m (LS mean; 95% CI: 18.35-83.49; P=0.0023). A statistically significant improvement in QoL with Actovegin compared with placebo was demonstrated within 24 weeks (LS mean 2.28; 95% CI: 0.88-3.68; P=0.0015). Actovegin demonstrated an acceptable safety and tolerability profile with minor differences from placebo. CONCLUSIONS: The results of this 12-week course of Actovegin demonstrated its superiority over placebo in the increase in ICD and ACD at weeks 2, 12 and 24 from the start of treatment. Actovegin has an acceptable safety and tolerability profile.