Efficacy and safety of omalizumab in Chinese patients with anti-histamine refractory chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non-sedating H1-antihistamines (H1AH) are the recommended first-line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20-week randomized, double blind, placebo-controlled, parallel-group study investigated the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: -4.23; 95% confidence interval [CI]: -5.70, -2.77; p < 0.001) and OMA150 (LSM: -3.79; 95% CI: -5.24, -2.33; p < 0.001) versus placebo. Incidence of treatment-emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.

Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties.

As a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50=0.18 µM and IC50=0.168 µM, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 µM was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K(i)=2.9 µM).

Immunogenicity of two diphtheria-tetanus-whole cell pertussis-hepatitis B vaccines in infants: a comparative trial.

AIM: Because of the high mother-to-infant transmissibility of hepatitis B (HB) infection, neonatal vaccination is necessary, but the further doses of HB vaccines can be combined with conventional diphtheria-tetanus-whole cell pertussis (DTPw) vaccines. We compared immunogenicity and reactogenicity of two tetravalent vaccines in Indian children, who after neonatal HB immunization, were vaccinated thrice with one of these vaccines. METHODS: In this open-label randomized study, 287 infants received a dose of an Indian- (Q-Vac (TM )) or European-made (Tritanrix-HB (TM )) tetravalent vaccine at age 6, 10, and 14 weeks. The ELISA antibodies were measured prior to the first and one month after the third dose. Immunogenicity was determined by measuring the seroprotection/seropositivity rates and geometric mean titres (GMT), whereas vaccine reactogenicity was elucidated with diary cards for 7 days following each dose. The potential unsolicited events were queried throughout the whole 3-month study period. RESULTS: Out of the 250 subjects who completed the study, 123 received the Indian and 127 the European vaccine. After 3 doses, the seroprotection/seropositivity rates were 99 % and 100% for diphtheria, 98% and 95% for tetanus, 89% and 94% for pertussis, and 100% and 100% for hepatitis B, respectively. GMT of tetanus antibodies was significantly higher with the Indian vaccine. Low-grade reactogenicity was rather similar in the two vaccine groups, the most common events being local pain, redness, swelling, fever, irritability, unusual crying, drowsiness, and non-specific gastrointestinal symptoms. CONCLUSIONS: Since both immunogenicity and reactogenicity of the two vaccines were almost identical, the Indian vaccine poses a good alternative to the costlier competitor vaccines.

A comparative study to evaluate the safety and immunogenicity of two lots of Haemophilus influenzae type-B conjugate vaccine manufactured at different scales.

OBJECTIVE: To compare the immunogenicity and safety of two different lots of SII Haemophilus influenzae type-B-tetanus toxoid conjugate (SII HibP(RO)) vaccine manufactured at different scales when given in 3-dose schedule. DESIGN: Phase IV, open label, comparative, randomized parallel group study. SETTING: Shirdi Sai Baba Hospital, Vadu Budruk, Pune and Pediatrics Department of King Edward Memorial Hospital Research Centre, Pune. SUBJECTS: 204 normal healthy infants of age 6-8 weeks at the time of first vaccination. METHODS: The eligible subjects received 3 doses of 0.5 ml of SII HibP(RO) vaccine of either lot depending upon randomization number, intramuscularly in right thigh in the EPI schedule of 6, 10 and 14 weeks. They also received concomitantly DTP-HB vaccine intramuscularly on left thigh and Oral Polio vaccine (OPV). Solicited reactions were captured for 7 days following each vaccination; the events beyond 7 days till day 28 were captured as unsolicited adverse events. Serious Adverse Events (SAEs) were looked for throughout the subject participation. Blood samples were collected at baseline (before the first dose) and one month after the third dose for anti-PRP (polyribosylribitol phosphate) antibodies. RESULTS: In both groups, more than 98% subjects achieved short-term seroprotection (anti-PRP ≥ 0.15 µg/ml) after 3 doses. The long-term seroprotection (anti-PRP ≥ 1 µg/ml) was 87% and 80% in infants receiving lot manufactured at industrial scale and small scale respectively. Short and long term seroprotection and GMTs increased significantly as compared to baseline in both the groups. Overall local pain (52% and 58%), redness (30% and 41%), swelling (34% and 44%), fever (6% and 6%) and irritability (52% and 50%) were reported in infants receiving lot manufactured at industrial scale and small scale respectively. Majority of the reactions were mild and resolved without any sequelae. Four SAEs, none of them causally related to the study vaccine, occurred during study. CONCLUSION: SII HibP(RO) vaccines manufactured in small and industrial scale are equally immunogenic, safe and confer adequate seroprotection to infants of 6-14 weeks of age. Scaling up production process has not affected the safety and immune response in the target population.