• Communications for Statistical Applications and Methods
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• v.16 no.1
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• pp.51-65
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• 2009

The purpose of a phase I clinical trial is to determine the maximum tolerated dose(MTD) of a new drug. This paper investigates the performance of standard method, continual reassessment method and accelerated titration designs in phase I clinical trials. Especially we study the precision and safety at the MTD of these methods. We utilize hyperbolic tangent function and power function to define dose-toxicity model. For each method, expected toxicity rate at MTD is computed and compared with target toxicity probability. We also suggest some modifications of these methods and show some improvements in performance.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Korean Journal of Radiology
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• v.23 no.9
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• pp.911-920
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• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.115-125
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• 2010

Objectives : The purpose of this study is to determine the effect of Bee-venom Acupuncture on upper limb spasticity control in stroke patients. Methods : Ten stroke patients with upper limb spasticity were randomly divided into two groups, a Bee-Venom Acupuncture group(group I) and a normal saline group(group II). After 1 week resting phase, this trial was used a cross-over trial. The numbers of Pharmacopuncture treatment were 3 times a week for 3 weeks. Modified Ashworth Scale(MAS), WMFT(Wolf Motor Function Test), The 10-second Test were used for evaluation of spasticity control before experiment, after 1 week, 2 weeks, 3 weeks. Results : Group I showed significant improvement(p<.05) in MAS, WMFT, The 10-second Test. But Group II showed no significant improvement(p<.05) in MAS, WMFT, The 10-second Test. The results showed significant difference in WMFT, The 10-second Test, but no significant difference in MAS between two groups. Conclusions : These results showed that Bee-venom Acupuncture might decrease upper limb spasticity and increase arm motor function in stroke patients. Further studies will be required to examine more cases in the long period for the effect on upper limb in spasticity by Bee-Venom Acupuncture.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7441-7447
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• 2015

Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.539-549
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• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• The Transactions of the Korean Institute of Electrical Engineers C
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• v.48 no.7
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• pp.533-541
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• 1999

Multi-discharge type ozonizer(MDO) using superposed silent discharge has been designed and manufactured. It consists of three electrodes( central electrode, internal electrode, and external electrode ) and double gaps( gap between central electrode and internal electrode, gap between internal electrode and external electrode ). Therefore, ozone is generated by superposing silent discharges generated between the gaps respectively. And the MDO consists of three types of superposed discharge ozonizers according to voltage appling method for each electrode ; A.C. high voltages are applied two of three electrodes with phase difference of 180[˚], the other electrode is a ground. This paper describes that discharge and ozone generation characteristics of MDO which comprising central electrode and internal electrode applied A.C. high voltages with phase difference of 180[˚] respectively, and the grounded external electrode. As a result, the maximum ozone concentration, generation, and yield can be obtained 10208[ppm], 6.4[g/h], and 280[g/kwh] respectively.

• Journal of the Korean Institute of Telematics and Electronics
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• v.12 no.5
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• pp.12-18
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• 1975

Triac phase controlled pre-regulator를 이용한 직류안정화전원에서 제어소자 전력소모를 촤소로 줄이기 위하여, 부하전류의 증가에 따라 제어소자 양단전압을 낮추어 주는 회로를 고안하여 부가하였다. 이렇게 하므로써 제어소자의 전력소모가 약 40%정도 감소되어 방열장치가 간단해지거나 전력용량을 증가할 수 있게 되었으며 열발산이 곤란한 monolithic I.C.화에 유용하도록 하였다. A method on minimizing the power dissipation in the control element of a series D.C. voltage regutator is devised. An additional control circuit which reduces the average voltage drop across the control element according to increasing the load current is attached :o the trial phase controlled pre-regulator system. It is verified that the power dissipation in the control element is reduced up to 40% by this. circuit arrangement. The heat sink system can be simplified and the capacity of tile handling power is also increased. It is expected that this circuit arrangement can be applied to I.C. fabrication.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.45-51
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.6
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• pp.802-810
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• 2000

A total of 120 finishing crossbred pigs ($Landrace{\times}Large$ $White{\times}Duroc$) with equal numbers of barrows and gilts weighing 58.5 kg body weight were used in a feeding trial, and 6 pigs (three of each sex) were used in a metabolic trial to investigate the effect of phase feeding. Finishing period was divided into two phases and 4 different diets were fed for those periods. Growth performance was not significantly different among treatments within the same sex. This result showed that 16% crude protein for early finishing period and 14% crude protein diet for late finishing period should be optimum. During the early finishing period, only feed intake was significantly different between sexes (p<0.01), but in late finishing period daily weight gain (p<0.001) and feed intake (p<0.01) of barrows were significantly higher than those of gilts. During the early finishing period, digestibilities of dry matter, protein and phosphorus were significantly higher in gilts than in barrows (p<0.05). However, there was no treatment effect within same sex during the early and late finishing period. During early finishing period, excretion of N of pigs fed 16% CP diet in early and 14% CP diet in late-finishing period was less than that of pigs fed 17% CP diet in early and 15% CP diet in late-finishing period (p<0.05), but the difference was not significant. During the late finishing period, N excretion with two phase feeding was reduced by 8.5% compared with single feeding. In gilts, total cost reduction by two phase feeding compared to single feeding was 9.1%, but in barrows it was just 3.19%. Relative margin increased with two phase feeding by 2.5% in gUts and 0.2% in barrows. There was a tendency that backfat thickness at 10th rib of gilts was thinner than that of barrows (p>0.05). Within the same sexes, there was no treatment effect on back fat thickness (p>0.05). Carcass grade was improved by two phase feeding compared to single feeding. Carcass grade of gilts was significantly better than that of barrows (p<0.001). From this results, it is concluded that finishing pigs could be fed two-phase diets to improve profit and reduce pollution.