• International Journal of Stem Cells
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• 제16권1호
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• pp.16-26
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• 2023

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

• 약학회지
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• 제50권6호
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• pp.386-392
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• 2006

Pramlintide, a synthetic analogue of human hormone amylin, is the first of a new class of amylinomimetic compounds. Present study was undertaken to compile and analyze the clinical trials of pramlintide, and thereby to facilitate the design of the bridging study for the earlier introduction of the drug, which might be needed by diabetes patients in Korea. Sixty-two articles from Pubmed and MEDLINE search were used to analyze the trials of pramlintide along with prescribing information and New Drug Application packet obtained form the manufacturer. The efficacy of the new drug was attributed to three mechanisms: delay of gastric emptying time, inhibition of post-prandial glucagon secretion, and reduction of food intake by enhanced satiety. Clinical trials consistently identified the effectiveness of the drug for the treatment of type 1and type 2 diabetes who have failed to achieve glycemic control despite optimal therapy with insulin. However, the six pivotal Phase III clinical trials were peformed with mostly caucasian and some black and hispanic people. None of the trials documented the proportion of either Asian or Korean participants. Since Korean diabetes patients show different epidemiology and characteristics in their disease state, it appears that the bridging study of pramlintide should be designed in the level of full scale Phase III clinical trial along with pharmacokinetic and pbarmacodynamic studies.

• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.265-271
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of etodolac in human serum was developed, validated, and applied to the pharmacokinetic study of etodolac. Etodolac and internal standard, ibuprofen were extracted from human serum by liquid-liquid extraction with hexane/isopropanol (95:5, v/v) and analyzed on a Luna C18(2) column with the mobile phase of 1% aqueous acetic acid-acetonitrile (4:6, v/v). Detection wavelength of 227 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 etodolac concentration $(1\;{\mu}g/mL)$ 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 $0.05-40\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 0.05 ${\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.00 to 110.00% for etodolac with overall precision (% C.V.) being 1.08-10.11%. The percent recovery for human serum was in the range of 76.73-115.30%. Stability studies showed that etodolac was stable during storage, or during the assay procedure in human serum. The peak area and retention time of etodolac 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 etodolac in human serum samples for the pharmacokinetic studies of orally administered Lodin XL tablet (400 mg as etodolac) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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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.

• 대한한방소아과학회지
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• 제38권1호
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• pp.55-77
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• 2024

Objectives This study aimed to analyze the registration status and characteristics of clinical trials on herbal medicine (HM) and medication interventions for simple obesity in children and adolescents. Methods All interventional clinical trials registered in the International Clinical Trials Registry Platform of the World Health Organization until December 12, 2024, were collected. The study design, interventions, inclusion and exclusion criteria, and outcome measures were extracted. Results A total of 24 clinical trials (23 medications and 1 HM) were analyzed. The most common study designs were single-center, randomized controlled, parallel, and phase 2. Placebo controls were used in 87.5% of the studies, blinding was used in 79.1%, and quadruple blinding was the most common. Informed consent was obtained from 70.8% of the participants. Among the oral medications (66.6%), metformin was the most common (25%). Among the non-oral medications (29.1%), exenatide (Bydureon) was the most common intervention (42.8%). Body mass index was the most commonly reported primary outcome measure (79.1%), with most assessments performed at 6 months. Conclusions Based on the characteristics of the medication interventional clinical trial design analyzed in this study, additional high-quality multicenter traditional Korean medicine trials need to be designed in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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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.

• Communications for Statistical Applications and Methods
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• 제16권1호
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• pp.51-65
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• 2009

제 1상 임상시험은 사람을 대상으로 처음 실시되므로 약물 투여의 안전성과 정확성이 신중히 고려되어야 한다. 따라서 제 1상 임상시험에서는 적은 수의 피험자를 통해 최대허용용량(maximum tolerated dose)을 정확하게 찾아야 한다. 제 1상 임상시험에서 최대허용용량을 결정하는 방법에는 표준방법(standard method), 연속재평가방법(continual reassessment method) 그리고 가속적정계획(accelerated titration designs) 방법이 있다. 본 연구에서는 동일한 모형에서 세 방법을 동시에 고려하여 최대허용용량의 안전성과 정확성을 살펴보았다. 또한 세 방법에 대해 최대허용용량에서 기대독성확률을 구하여 비교하였다. 그리고 ATD와 CRM의 단점을 보완한 수정된 ATD와 수정된 CRM을 포함하여 여러 방법들을 동일한 모형에서 동시에 그 성능을 비교하였다.

• 한국임상약학회지
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• 제29권2호
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• pp.71-78
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• 2019

Objective: This study aimed to provide efficacy and safety information on the use of erenumab for prevention of episodic and chronic migraines. Methods: The keywords "Erenumab and migraine" were used to search the PubMed database to then compile efficacy and safety data for erenumab. Data from relevant Phase 2 and Phase 3 clinical trials were analyzed, using RevMan for statistical analysis. Results: Three clinical trials (one Phase 2 and two Phase 3 studies) were retrieved. All three trials used the same primary endpoint (change from baseline in monthly migraine days (CBMD)) to evaluate efficacy and safety of erenumab use for prevention of episodic and chronic migraines. Subcutaneous doses of erenumab (70 or 140 mg) were administered monthly in each trial, for 3 months (Studies 2, and 3) or 6 months (Study 1). The mean differences in CBMD in the 70 mg and 140 mg erenumab arms were -1.36 and -1.98, respectively, compared to that in the placebo arm. Some adverse events, such as nasopharyngitis and upper respiratory tract infection, were reported, but no differences in safety between erenumab and placebo were found to be significant. Conclusions: Erenumab showed superior efficacy in prevention of migraines compared to placebo. However, additional information regarding the long-term safety of erenumab should be collected. Therefore, post-marketing surveillance for adverse events is needed.

• Journal of Pharmaceutical Investigation
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• 제35권6호
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• pp.437-443
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of a major metabolite of terfenadine, fexofenadine, in human serum was developed, validated, and applied to the pharmacokinetic study of terfenadine. Fexofenadine and internal standard, haloperidol were extracted from human serum by liquid-liquid extraction with acetonitrile and analyzed on a $Symmetry^{TM}$ C8 column with the mobile phase of 1% triethylamine phosphate (pH 3.7)-acetonitrile (67:33, v/v, adjusted to pH 5.6 with triethylamine). Detection wavelength of 230 nm for excitation, 280 nm for emission 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 fexofenadine concentration (50 ng/mL) with respect to its peak area and retention time. In addition, 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 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 10 ng/mL, which was sensitive enough for the pharmacokinetic studies of terfenadine. The overall accuracy of the quality control samples ranged from 95.70 to 114.58% for fexofenadine with overall precision (% C.V.) being 3.53-14.39%. The relative mean recovery of fexofenadine for human serum was 90.17%. Stability studies (freeze-thaw, short-term, extracted serum sample and stock solution) showed that fexofenadine was stable during storage, or during the assay procedure in human serum. However, the storage at $-70^{\circ}C$ for 4 weeks showed that fexofenadine was not stable. The peak area and retention time of fexofenadine 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 fexofenadine in human serum samples for the pharmacokinetic studies of orally administered Tafedine tablet (60 mg as terfenadine) at three different laboratories, demonstrating the suitability of the method.

• Archives of Plastic Surgery
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• 제42권6호
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• pp.721-728
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• 2015

Background We conducted this clinical study to compare the efficacy and safety between Neuramis Deep and Restylane in the correction of nasolabial folds. Methods In this phase III, randomized, multi-center, double-masked, matched-pairs, active-controlled trial (ClinicalTrials.gov Identifier: NCT01585220), we evaluated a total of 67 subjects (n=67). All the subjects underwent Neuramis Deep treatment on one side and Restylane on the contralateral side of the bilateral nasolabial folds at a ratio of 1:1. To compare the efficacy of Neuramis Deep and Restylane, we evaluated the Wrinkle Severity Rating Scale scores and those of the Global Aesthetic Improvement Scale. In addition, we compared the safety of Neuramis Deep and Restylane based on adverse events, physical examination, and clinical laboratory tests. Results Neuramis Deep was not inferior in improving the nasolabial folds as compared with Restylane. In addition, there was no significant difference in the efficacy between Neuramis Deep and Restylane. There were no significant differences in safety parameters between Neuramis Deep and Restylane. Conclusions In conclusion, our results indicate that Neuramis Deep may be a safe, effective material for improving the nasolabial folds. However, further studies are warranted to compare the tolerability of Neuramis Deep and Restylane based on histopathologic findings.