Long-term Persistence of Immunogenicity After Primary Vaccination and Response to Booster Vaccination With Typhoid Conjugate Vaccine: Results of a Phase IV Extension Study

Objective: To evaluate the persistence of antibodies three years after primary vaccination with typhoid conjugate vaccine (TCV) of either Cadila Healthcare Ltd. (Cadila-TCV) or Bharat Biotech International Ltd. (Bharat-TCV) administered in a previous phase II/III study, and to study the booster dose response to Cadila-TCV. Methods: This was an open-label, phase IV extension study conducted in tertiary care and multispecialty hospitals in India. 112 subjects (Cadila-TCV-57, Bharat-TCV-55) who had participated in previous study were enrolled. Of these, eligible subjects received a single-dose of Cadila-TCV and were followed-up for 28 days post-booster. Primary outcome was persistence of antibodies 3 years after primary vaccination and seroconversion (?4-fold rise in antibody titre from baseline) 28 days postbooster. Safety was based on reported adverse events (AEs) post-booster. Results: The baseline GMT reported in the current study was significantly higher than pre-vaccination GMT reported in the previous study. 89/112 (79.5%) subjects had antibody titer ?10 IU/mL at baseline; eligible subjects (n=17) who had baseline antibody titre <10 IU/mL were administered booster dose. All the vaccinated subjects showed seroconversion post-booster. The GMTs reported at 10 days and 28 days post-booster were significantly higher as compared to GMTs reported after primary vaccination in previous study. 4 (23.5%) vaccinated subjects reported 9 AEs; all were solicited and of mild/moderate intensity. Conclusion: There was a significant persistence of immunogenicity after primary vaccination with both the TCVs, and robust immune response after booster vaccination with Cadila-TCV.

Cinitapride Extended-Release Tablets Versus Cinitapride Immediate-Release Tablets in the Treatment of Functional Dyspepsia and Gastroesophageal Reflux Disease : A Randomized Clinical Trial.

Prokinetics are commonly used for Functional Dyspepsia (FD) and GastroEsophageal Reflux Disease (GERD). Aims and Objectives: To evaluate the safety and efficacy of cinitapride Extended-Release (ER) tablets versus conventional cinitapride Immediate-Release (IR) tablets for the treatment of FD and GERD. Materials and Methods: Patients with FD and GERD received either cinitapride ER 3 mg tablets OD or cinitapride IR 1 mg tablets TID for 4 weeks in this randomized, multicentre study. Change in the mean intensity score of gastrointestinal (GI) symptoms (overall and individual) at the end of the study and at each weekly follow up visit as compared to baseline, patients with complete resolution of GI symptoms, patients with > 50% reduction from baseline in overall intensity score, rescue medication use and overall efficacy were recorded. The safety variables were reported adverse events (AEs), laboratory parameters, electrocardiogram, and overall tolerability. Unpaired t test, chi square test or Fisher’s exact test were used for analysis. p < 0.05 was considered significant. Results: Total 218 patients were enrolled Cinitapride ER tablets were non-inferior (non-inferiority margin -2.5) to cinitapride IR tablets for the change in the mean overall GI symptom intensity score at the end of the study as compared to the baseline (treatment difference - 0.2 (95% CI: -2.2, 1.7)); also, no significant difference was found for other efficacy variables (p > 0.05). Eight AEs of mild-to-moderate intensity were reported. There was also no difference in the overall tolerability between the study groups (p = 0.875). Conclusions : Both the study treatments were comparable in terms of safety and efficacy for the treatment of FD and GERD.

Efficacy and Safety of Pegfilgrastim in Indian Patients.

Context: Pegfilgrastim, a pegylated recombinant granulocyte colony stimulating factor, promotes the hematopoietic recovery after cytotoxic chemotherapy and is marketed in India as PegstimTM. Aims: This post marketing surveillance study was undertaken to evaluate the efficacy and safety of PegstimTM in clinical practice in Indian patients. Material and Methods: Investigators participating in this post marketing surveillance were asked to capture data of all the patients who were given PegstimTM along with cytotoxic chemotherapy for their underlying malignancy. PegstimTM was given as a single subcutaneous dose approximately 24 hours after administration of cytotoxic chemotherapy and patients were followed up for 14 days with blood counts at baseline and every alternate day. Each cycle of chemotherapy in which PegstimTM was administered was considered as a distinct patient entity for efficacy and safety analysis. Results: PegstimTM injections were used in 213 patients and led to an increase in Absolute Neutrophil Count (ANC) as early as 2 days after administration of the drug with mean percent increase in ANC of 129.8 ± 210.9% at the end of 14 days. The overall incidence of moderate-severe (grade III/IV) febrile neutropenia in the total population studied was 6.1% (13 patients). Intravenous antibiotics were used in 10 (4.7%) patients while 4 (1.9%) patients required hospitalization. A total of 57 adverse events were reported in 32 patients during the entire course of the study, the most common being musculoskeletal pain in 22 (10.3%) patients. Conclusions: The results from this post marketing surveillance study support the efficacy and tolerability of PegstimTM used for preventing neutropenia across various tumor types and regimens in Indian patients.

Efficacy and safety of a nano-emulsion gel formulation of adapalene 0.1% and clindamycin 1% combination in acne vulgaris: A randomized, open label, active-controlled, multicentric, phase IV clinical trial.

Background: Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients. Aims: To assess the comparative efficacy and safety of a nano-emulsion gel formulation of adapalene and clindamycin combination with its conventional formulation in the treatment of acne vulgaris of the face. It was a prospective, randomized, open label, active-controlled, multicentric, clinical trial. Methods: Eligible patients suffering from acne vulgaris of the face were randomized to receive once-daily treatment with a nano-emulsion gel or conventional gel formulation of adapalene 0.1% and clindamycin (as phosphate) 1% combination for 12 weeks. Total, inflammatory and noninflammatory lesion counts, with grading of acne severity were carried out on a monthly basis. Safety assessments were done to determine the comparative local and systemic tolerability. Two-tailed significance testing was carried out with appropriate statistical tests, and P-values < 0.05 were considered as significant. Results: 209/212 patients enrolled in the study were eligible for efficacy and safety assessments in both nano-emulsion gel (118/119 patients) and conventional gel (91/93 patients) groups. Significantly better reductions in total (79.7% vs. 62.7%), inflammatory (88.7% vs. 71.4%) and noninflammatory (74.9% vs. 58.4%) lesions were reported with the nano-emulsion gel as compared to the conventional gel (P < 0.001 for all). Mean acne severity score also reduced significantly more with the nano-emulsion formulation (1.9 ± 0.9 vs. 1.4 ± 1.0; P < 0.001) than the comparator. Significantly lower incidence and lesser intensity of adverse events like local irritation (4.2% vs. 19.8%; P < 0.05) and erythema (0.8% vs. 9.9%; P < 0.05) were recorded with the nano-emulsion gel. Conclusions: The nano-emulsion gel formulation of adapalene and clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation for the treatment of acne vulgaris in Indian patients. Further studies can elucidate the comparative treatment benefits of this nano-emulsion gel formulation.