PURPOSE: A phase I clinical trial was conducted to evaluate the immunogenicity and safety of newly developed egg-cultivated trivalent inactivated split influenza vaccine (TIV) in Korea. MATERIALS AND METHODS: The TIV was administered to 43 healthy male adults. Subjects with high pre-existing titers were excluded in a screening step. Immune response was measured by a hemagglutination inhibition (HI) assay. RESULTS: The seroprotection rates against A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2009 were 74.42% [95% confidence interval (CI): 61.38–87.46], 72.09% (95% CI: 58.69–85.50), and 86.05% (95% CI: 75.69–96.40), respectively. Calculated seroconversion rates were 74.42% (95% CI: 61.38–87.46), 74.42% (95% CI: 61.38–87.46), and 79.07% (95% CI: 66.91–91.23), respectively. There were 25 episodes of solicited local adverse events in 21 subjects (47.73%), 21 episodes of solicited general adverse events in 16 subjects (36.36%) and 5 episodes of unsolicited adverse events in 5 subjects (11.36%). All adverse events were grade 1 or 2 and disappeared within three days. CONCLUSION: The immunogenicity and safety of TIV established in this phase I trial are sufficient to plan a larger scale clinical trial.
Adult* ; Hemagglutination ; Humans ; Influenza Vaccines* ; Influenza, Human* ; Korea ; Male ; Mass Screening ; Seroconversion

BACKGROUND: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg is taken three-times daily. A controlled release formulation of levodropropizine (levodropropizine CR) 90 mg was developed, which can be taken twice daily. The aim of this study was to evaluate the safety and pharmacokinetic characteristics after multiple oral administrations of levodropropizine CR 90 mg tablets in healthy male volunteers. METHODS: A randomized, open-label, cross-over study was conducted in 24 healthy male volunteers. Each subject received levodropropizine syrup 60 mg three times daily or levodropropizine CR 90 mg twice daily for 3 days. Blood samples for pharmacokinetic analysis were collected pre-dose and up to 24 hours on day 4. Pharmacokinetic analysis was conducted by non-compartmental method. Safety assessments including monitoring adverse events, laboratory tests, vital signs, physical examinations and ECGs were performed throughout the study. RESULTS: A total of 20 male volunteers completed the study. The maximum steady-state plasma concentration (Css,max) of levodropropizine syrup and levodropropizine CR were 313.28 ng/mL and 285.31 ng/mL and time to reach Css,max (Tmax,ss) were 0.48 hr and 0.88 hr, respectively. The area under the concentration-time curve to the last measured concentration of two groups were 2345.36 hr x ng/mL and 2553.81 hr x ng/mL, respectively. There was no serious adverse event. CONCLUSION: Levodropropizine CR 90 mg tablet was safe and well-tolerated when administered twice daily for 3 days. No statistically significant differences were seen in Css,max and AUCss,24hr between the two formulations. This study provided pharmacokinetic evidences that the twice-daily dosing regimen of levodropropizine 90 mg may substitute the conventional 3-times-daily regimen of levodropropizine 60 mg.
Administration, Oral ; Cross-Over Studies ; Electrocardiography ; Humans ; Male* ; Methods ; Neuropeptides ; Pharmacokinetics* ; Physical Examination ; Plasma ; Tablets ; Vital Signs

Background: The risk of secondhand smoke (SHS) is gradually becoming apparent, and as smoking cessation zones are expanding, the exposure to SHS in workplaces, homes, and public places is decreasing. The objective of this study was to evaluate the actual exposure to SHS in nonsmokers. Methods: This study used data from 2008 to 2011 and 2014 to 2018 from the Korean National Health and Nutrition Examination Survey (KNHANES). The urine cotinine concentration values were compared by the geometric mean according to sex, age group, and rurality for non-smokers aged 19 years or older who were tested for urine cotinine. Results: The overall trend of urine cotinine concentration in Korean adult non-smokers have shown a decline since 2011. It gradually decreased from 2.82 ng/mL in 2010 to 0.50 ng/mL in 2016 but slightly increased to 0.79 ng/mL in 2018. Both male and female showed this trend. The decline tended to be lower in those aged 60 years and older, with higher urine cotinine concentrations in the recent 3 years in the rural than in urban residents. Conclusion The urinary cotinine concentration levels in Korean non-smokers increased from 2008 to 2010, then decreased till 2016, but gradually increased thereafter. This is possibly due to limiting the exposure to SHS through expanding the smoking area. Furthermore, a policy to lower the smoking rate with strict implementation and monitoring of the existing policy will be needed.

Statistical analysts engaged in typical clinical trials often have to confront a tight schedule to finish massive statistical analyses specified in a Standard Operation Procedure (SOP). Thus, statisticians or not, most analysts would want to reuse or slightly modify existing programs. Since even a slight misapplication of statistical methods or techniques can easily drive a whole conclusion to a wrong direction, analysts should arm themselves with well organized statistical concepts in advance. This paper will review basic statistical concepts related to typical clinical trials. The number of variables and their measurement scales determine an appropriate method. Since most of the explanatory variables in clinical trials are designed beforehand, the main statistics we review for clinical trials include univariate data analysis, design of experiments, and categorical data analysis. Especially, if the response variable is binary or observations collected from a subject are correlated, the analysts should pay special attention to selecting an appropriate method. McNemar's test and multiple McNemar's test are respectively recommended for comparisons of proportions between correlated two samples or proportions among correlated multi-samples.
Appointments and Schedules ; Arm ; Chi-Square Distribution ; Cross-Over Studies ; Statistics as Topic ; Weights and Measures

BACKGROUND: Serum uric acid (UA) has been found to be associated with hypertension, obesity, dyslipidemia, and metabolic syndrome; however, its role as an independent risk factor of cardiovascular disease (CVD) is still controversial. There have been very few studies reporting an association between UA levels and carotid intima-media thickness (CIMT), especially in women.METHODS: The study included 245 subjects whose CIMT was evaluated between February 2016 and December 2017 at a health promotion center. We divided the population into two groups on the basis of menopausal status: premenopausal women (n=78) and postmenopausal women (n=167). We measured blood pressure, serum lipid profile, fasting blood glucose (FBG), and creatinine and UA levels. CIMT was measured using high-resolution B-mode ultrasonography.RESULTS: UA levels and CIMT were higher in postmenopausal women (P=0.029, P < 0.001). In premenopausal women, age (r=0.438), body mass index (r=0.373), UA (r=0.205), and FBG (r=0.336) were associated with CIMT, whereas in postmenopausal women, age (r=0.326), body mass index (r=0.167), UA (r=0.166), systolic blood pressure (r=0.200), and HDL-cholesterol (r=−0.140) were associated with CIMT. The UA level was independently associated with CIMT in premenopausal women (β=0.208, P=0.031), whereas age was the only factor independently associated with CIMT in postmenopausal women (β=0.253, P=0.002). Women in the highest tertile of uric acid level exhibited a higher CIMT than did those in the lowest tertile after age adjustment (P for trend < 0.001).CONCLUSION: UA may be an independent risk factor for CIMT, suggesting that UA is a risk factor for the early detection of CVD, especially in premenopausal women.
Blood Glucose ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Carotid Intima-Media Thickness ; Creatinine ; Dyslipidemias ; Fasting ; Female ; Health Promotion ; Humans ; Hypertension ; Menopause ; Obesity ; Risk Factors ; Ultrasonography ; Uric Acid

BACKGROUND: Elevated serum uric acid (UA) level is a known risk factor for atherosclerotic diseases, including peripheral arterial disease (PAD). PAD is easily diagnosed by determining the ankle-brachial index (ABI). The relationship between serum UA and subclinical atherosclerotic diseases remains controversial. We therefore aimed to explore an independent association between UA and ABI in healthy Korean men.METHODS: A cross-sectional study was conducted in 664 male participants aged ≥19 years who visited our Center for Health Promotion. The ABI and serum UA were determined for all participants and the relationship between these parameters and between ABI and other variables was assessed with the Pearson correlation coefficient. Multiple regression analysis was conducted to determine an independent correlation between serum UA and ABI after adjustment for certain variables. Analysis of covariance was employed to identify a trend in the ABI relative to UA quartiles.RESULTS: The ABI correlated inversely with UA and variables such as body mass index, diastolic blood pressure, heart rate, total cholesterol, triglycerides, and low-density lipoprotein-cholesterol. UA showed an independent inverse correlation with the ABI after serial adjustment for these variables (β=−0.265, P < 0.001). A decreasing trend in the ABI was observed with increasing UA quartile (P < 0.001).CONCLUSION: UA shows an independent inverse correlation with ABI in healthy Korean men.
Ankle Brachial Index ; Ankle ; Atherosclerosis ; Blood Pressure ; Body Mass Index ; Cholesterol ; Cross-Sectional Studies ; Health Promotion ; Heart Rate ; Humans ; Male ; Peripheral Arterial Disease ; Risk Factors ; Triglycerides ; Uric Acid

BACKGROUND: The objective of this study was to compare the pharmacokinetics and safety between newly developed sildenafil (Please Orally Soluble Film) and sildenafil citrate (VIAGRA(R)) after single oral administration in healthy Korean male subjects. METHODS: A randomized, open-label, single dose, 2-way crossover study was conducted in 50 healthy male subjects. Each sequence group consisted of 25 subjects, received a single oral 50 mg dose of Please Orally Soluble Film (test formulation) or VIAGRA(R) (reference formulation) by study period. Blood samples were obtained during a 24-hour period after dosing. Sildenafil and its metabolite concentrations were determined using validated LC-MS/MS. A non-compartmental pharmacokinetic analysis was performed. Safety was assessed through monitoring of adverse events, vital sign check-up, physical examination, laboratory tests and electrocardiography. RESULTS: All enrolled participants completed the study. The point estimates and 90% confidence intervals of log transformed C(max) and AUC(last) of the test formulation in comparison to those of reference formulation were 0.9294(0.8353 - 1.0341) and 0.9415 (0.8869 - 0.9994) respectively. The analysis of variance showed no significant influences of formulation, sequence and period on the pharmacokinetic parameters. The frequencies of adverse events were not statistically different between the formulations. No serious adverse event was observed or reported. CONCLUSION: Please Orally Soluble Film could be considered bioequivalent to VIAGRA(R) and had similar safety properties in healthy Korean male subjects.
Administration, Oral ; Citric Acid ; Cross-Over Studies ; Humans ; Male ; Physical Examination ; Piperazines ; Purines ; Sulfones ; Sildenafil Citratea ; Vital Signs