Exploring the divergence in perspectives on clinical trial operations in South Korea during the COVID-19 pandemic: a comparison of a trial site and sponsors.

Introduction: During the COVID-19 pandemic, novel clinical trial methods known as decentralized clinical trials (DCTs) were rapidly introduced. The attitude toward operating clinical trials and perspectives on DCTs may differ between clinical trial sites and sponsors. The impact of the COVID-19 pandemic on clinical trials was investigated for a society of sponsors and a trial site in South Korea. Methods: The current difficulties and future perspectives on clinical trials were assessed and compared between the site and sponsors. Results: Both the site and sponsors reported on their experiences with the challenges of conducting clinical trials during the pandemic era. While 64% of personnel from the site judged that the difficulties were solved by their own solutions, 67.6% of personnel from sponsors considered cooperation with trial sites as a key solution to overcome the difficulties. While half of the personnel from the site were skeptical of the changes in trial operation methods, the sponsors expected the institutionalization of DCT elements. Conclusion: In conclusion, with varying attitudes, sponsors and sites attempted to overcome the challenges of conducting clinical trials during the pandemic era. To conduct clinical trials effectively, both sponsors and sites must work closely together to find solutions with efficient communication. For the successful implementation of new tools such as DCTs, the government needs to solicit support from sponsors and sites and change regulations.

Pharmacokinetics and Food Effect Between a 100-mg Sustained-Release Tablet and a 50-mg Immediate-Release Tablet of Vildagliptin in Healthy Subjects.

Vildagliptin is one of the dipeptidyl peptidase-4 inhibitors. This study aimed to compare vildagliptin exposure between 50-mg immediate-release (IR) and 100-mg new sustained-release (SR) tablets, and evaluate the food effect on the pharmacokinetics (PKs) of vildagliptin. A randomized, open-label, 3-period, 3-treatment, 6-sequence crossover study was conducted on healthy subjects. During each period, subjects received the SR tablet either in the fasted (T1) or high-fat fed (T2) state once a day, or IR tablets administered twice a day in the fasted state (R). Blood samples for PK analysis were obtained serially up to 24 hours after dosing. Thirty-four subjects completed the study. The geometric mean ratios for the Cmax and AUC0-24h of T1 to R were 1.15 and 0.89, respectively. The corresponding values of T2 to T1 were 0.94 and 1.07, respectively. Vildagliptin exposure over 24 hours was similar between the SR and IR tablets. In addition, the PK profiles of the SR tablets were not altered by food. The SR tablets can be administered without a food effect and be an alternative option to IR tablets.

No drug-drug interactions between selective prolyl-tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants.

Bersiporocin, a potent and selective prolyl-tRNA synthetase inhibitor, is expected to show a synergistic effect with pirfenidone or nintedanib in patients with idiopathic pulmonary fibrosis. To validate the combination therapy of bersiporocin with pirfenidone or nintedanib, a randomized, open-label, two-part, one-sequence, three-period, three-treatment study was designed to evaluate the effect of drug-drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric-coated bersiporocin tablet were evaluated after single and multiple administrations. The potential effects of cytochrome P450 2D6 (CYP2D6) genotyping on bersiporocin pharmacokinetics and DDI were also explored. In Part 1, participants were sequentially administered a single dose of pirfenidone 600 mg, a single dose of bersiporocin 150 mg followed by multiple doses, and bersiporocin in combination with pirfenidone. In Part 2, participants were sequentially administered a single dose of nintedanib 150 mg, multiple doses of bersiporocin 150 mg, and bersiporocin in combination with nintedanib. Forty-six participants completed the study. There was no significant pharmacokinetic DDI between bersiporocin, and pirfenidone or nintedanib. All adverse events (AEs) were mild to moderate and did not include serious AEs, suggesting bersiporocin alone or in combination therapy were well-tolerated. The newly formulated bersiporocin 150 mg tablet showed a moderate accumulation index. There was no significant difference in the pharmacokinetic profiles after administration of bersiporocin alone or in combination therapy between CYP2D6 phenotypes. In conclusion, there are no significant DDI regarding the pharmacokinetics, safety, and tolerability of bersiporocin administration with pirfenidone or nintedanib.

Size-reduced fexuprazan 20 mg demonstrated the optimal bioavailability and bioequivalence with the reference formulation.

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8-1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892-1.2265) for the maximum plasma concentration and 1.0530 (0.9611-1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations. The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

An Open Label, Multi-Center, Non-Interventional Post-Marketing Surveillance to Monitor the Safety and Efficacy of ALTARGO® (Retapamulin) Administered in Korean Patients According to the Prescribing Information.

BACKGROUND: With the approval of topical retapamulin ointment in 2011, it was officially required to conduct a post-marketing surveillance (PMS) study to obtain further data of its safety profile and effectiveness, in accordance with the requirement of the Korean Ministry of Food and Drug Safety (MFDS). OBJECTIVE: This study had prospectively designed to monitor safety and tolerability with the effectiveness of topical retapamulin in clinical practices. METHODS: Open label, multi-center, non-interventional observational study was done from May 2011 to October 2015. All subjects had bacterial skin infections of locally approved prescribing information accordingly. The study mainly focused on safety issues in the local target population (3,612 eligible subjects). And, drug effectiveness was also evaluated by physicians. RESULTS: The incidence of adverse events (AEs) and adverse drug reactions (ADRs) were 2.53% and 0.97%, respectively. In terms of the incidence of unexpected AEs and ADRs, 1.45% and 0.33%, and for the incidence of serious AEs, 0.28%, whereas no serious ADRs reported. And, the effectiveness of topical retapamulin rate was 96.1% (1,697 of total 1,765 subjects). CONCLUSION: Topical retapamulin is to be well-tolerated and effective in patients with bacterial skin infections of locally approved prescribing information.

Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia.

BACKGROUND: After the approval of dutastride for androgenic alopecia (AGA) in 2009, Korean authority required a post-marketing surveillance to obtain further data on its safety profile. OBJECTIVE: The objective was to monitor adverse events (AEs) of dutasteride 0.5 mg in Korean AGA male patients in a clinical practice environment. METHODS: Open label, multi-center, non-interventional observational study was done from July 2009 to July 2013. AGA subjects (18~41 years of age) with no experience of dutasteride were enrolled. Dosage regimen was recommended according to the prescribing information. The incidences of any AEs, serious adverse events (SAEs), and adverse drug reactions (ADRs) were evaluated. Multiple logistic regression method was used to identify risk factors related to ADRs. Effectiveness was generally evaluated by physicians. RESULTS: During study period, 712 subjects were enrolled. The subjects of 29.3±6.0 years old exposed to dutasteride for 204.7±161.5 days. One hundred and ten (15.4%) of subjects reported 138 AEs. Four subjects (0.6%) reported 5 SAEs (right radius fracture, 2 events of chronic follicular tonsillitis, influenza infection, and acute appendicitis). Sixty-six subjects (9.3%) reported 80 ADRs. Most frequent ADRs were libido decreased (9 subjects, 1.3%), dyspepsia (8 subjects, 1.1%), impotence (7 subjects, 1.0%), and fatigue (5 subjects, 0.7%). Other interested ADRs were sexual function abnormality (4 subjects, 0.6%), gynecomastia (2 subjects, 0.3%), and ejaculation disorder (1 subject, 0.1%). Most subjects (78.6%) showed overall improvement after treatment of dutasteride in the effectiveness. CONCLUSION: Dutasteride 0.5 mg is to be well-tolerated in 18 to 41 years old AGA patients in a clinical practice environment.

Changing Clinical Characteristics according to Insulin Resistance and Insulin Secretion in Newly Diagnosed Type 2 Diabetic Patients in Korea.

BACKGROUND: The role of increased insulin resistance in the pathogenesis of type 2 diabetes has been emphasized in Asian populations. Thus, we evaluated the proportion of insulin resistance and the insulin secretory capacity in patients with early phase type 2 diabetes in Korea. METHODS: We performed a cross-sectional analysis of 1,314 drug-naive patients with newly diagnosed diabetes from primary care clinics nationwide. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance, which was defined as a HOMA-IR ≥2.5. Insulin secretory defects were classified based on fasting plasma C-peptide levels: severe (<1.1 ng/mL), moderate (1.1 to 1.7 ng/mL) and mild to non-insulin secretory defect (≥1.7 ng/mL). RESULTS: The mean body mass index (BMI) was 25.2 kg/m(2); 77% of patients had BMIs >23.0 kg/m(2). Up to 50% of patients had central obesity based on their waist circumference (≥90 cm in men and 85 cm in women), and 70.6% had metabolic syndrome. Overall, 59.5% of subjects had insulin resistance, and 20.2% demonstrated a moderate to severe insulin secretory defect. Among those with insulin resistance, a high proportion of subjects (79.0%) had a mild or no insulin secretory defect. Only 2.6% of the men and 1.9% of the women had both insulin resistance and a moderate to severe insulin secretory defect. CONCLUSION: In this study, patients with early phase type 2 diabetes demonstrated increased insulin resistance, but preserved insulin secretion, with a high prevalence of obesity and metabolic syndrome.

Impact of global risk assessment on the evaluation of hypertensive patients treated by primary care physicians in Korea (a Nation-Wide, Multi-Center, Observational, Cross-Sectional, Epidemiologic Study to Evaluate the Proportion of Cardiovascular Risk Factors in Korean hypertensive patients: WONDER study).

Global cardiovascular risk evaluation and stratification is essential to identify high-risk hypertensive patients. However, it is uncertain how often the strategy is executed in real clinical practice. We sought to evaluate whether global risk evaluation might change the risk stratification in Korean hypertensive patients treated by primary care physicians. A total of 3109 hypertensive patients were analyzed. The mean age was 62.3±11.3 years, and 1502 (48.3%) of the participants were male. The global risk evaluation revealed that 1862 patients (59.9%) were classified as having high- or the very high-risk. High-risk patients were older and obese, and had a male predominance, a longer duration of hypertension and a low HDL-cholesterol. The systolic and diastolic blood pressures (BP) were significantly higher in the high-risk group (P<0.0001). However, combination antihypertensive therapy was more common in the low-risk group (P=0.0265). A total of 2155 patients (69.3%) were reclassified into the higher or the lower-risk group by performing additional tests. In a multivariate logistic regression analysis, age, body mass index, BP, metabolic syndrome, left ventricular hypertrophy and chronic kidney disease were independent factors associated with risk reclassification with global risk evaluation. In conclusion, although the majority of hypertensive patients treated by the primary care physicians were in the high- or very high-risk group, their risk levels were not appropriately stratified. However, simple additional tests enhanced the risk evaluation of hypertensive patients. Accordingly, comprehensive cardiovascular risk stratification should be undertaken in all hypertensive patients.

Influence of insurance benefit criteria on the administration rate of osteoporosis drugs in postmenopausal females.

BACKGROUND: Preventive measures need to be implemented to lower the incidence of osteoporotic fractures. Osteoporotic fractures increase morbidity and mortality as well as impose a socioeconomic burden; however, current research is limited to the administration rates of osteoporosis drugs for Korean postmenopausal females. METHODS: This study represents a nationwide, observational, and cross-sectional survey that investigates the administration rates of osteoporosis drugs based upon a bone mineral density (BMD) test performed on Korean postmenopausal patients who visited outpatient orthopedic clinics. BMD test results were examined in postmenopausal female patients (50 to 80 years of age); subsequently, the patients were classified into an osteoporosis group, osteopenia group, and normal group. The administration rates of osteoporosis drugs and bisphosphonates were then analyzed. The osteoporosis group was subdivided into a T-score less than -3.0 group and a T-score between -3.0 and -2.5 group that were separately analyzed. RESULTS: Based on the lumbar spine BMD, the rate of administration of osteoporosis drugs in the osteoporosis group was 42.1%, which was significantly higher compared to the osteopenia group or normal group. A significantly low bone mineral density was observed in patients who were administered bisphosphonates. Based on the lumbar spine BMD, the administration rate of osteoporosis drugs in the group with a T-score between -3.0 and -2.5 (34.2%) was significantly lower than the group with a T-score less that -3.0 (46.2%). The bisphosphonate administration rate was also significantly low; however, the administration rate for osteoporosis drugs was significantly lower than that of the osteopenia group. CONCLUSIONS: Only about 40% of Korean postmenopausal female patients with osteoporosis were administered osteoporosis drugs. The administration rate in patients with a T-score between -3.0 and -2.5 was particularly low and active treatment to prevent osteoporotic fractures is required in this group.

Prevalence of ocular symptoms in patients with allergic rhinitis: Korean multicenter study.

BACKGROUND: Allergic rhinitis (AR) is often accompanied by multiple ocular symptoms. This study aimed to evaluate the prevalence of ocular symptoms and the impact of ocular symptoms on the quality of life in patients with AR. METHODS: One thousand one hundred seventy-four patients with AR were enrolled from 24 centers in Korea. They were classified into four groups according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guideline and also classified into perennial AR (PAR) and seasonal AR groups. All patients were asked to complete the questionnaire regarding the presence of ocular symptoms, such as eye itching, watery eyes, and red eyes. The correlation between ocular symptoms and the rest of the quality-of-life areas in the Mini-Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) was also asked. RESULTS: Seven hundred nineteen (61.2%) of 1174 patients had ocular symptoms. In detail, the numbers of patients with eye itching, watery eyes, red eyes, and other ocular symptoms were 605 (51.5%), 313 (26.7%), 207 (17.6%), and 66 (5.6%), respectively. Female patients (72.5%) complained of ocular symptoms more commonly than male patients (55.1%). The patients with moderate-severe persistent AR showed the highest prevalence of ocular symptoms. The correlation coefficients between ocular symptoms and the rest of the quality-of-life areas in the Mini-RQLQ were statistically significant (p < 0.05). CONCLUSION: Sixty-one percent of Korean AR patients experienced ocular symptoms. The patients who were women and had PAR and more severe AR showed higher prevalence of ocular symptoms. The ocular symptoms might have a significant impact on the quality of life in patients with AR.

A Validation Study for the Korean Version of Chronic Obstructive Pulmonary Disease Assessment Test (CAT).

BACKGROUND: Health status measure is not only important for clinical research studies but also for clinical practices of chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to evaluate the validity of the Korean Version of COPD Assessment Test (CAT) in primary care clinics as well as in referral hospitals. METHODS: Smokers or ex-smokers, aged 40 years or older, with a smoking history of >10 pack-years; and a COPD diagnosis in the past 6 months or more, were recruited from 4 primary care clinics and 2 referral hospitals. Demographic, medical, and spirometry data was collected from patients who completed the CAT and St. George Respiratory Questionnaire (SGRQ), and had their dyspnea been assessed. The primary endpoint was the correlation between of the Korean version of CAT with SGRQ in patients with COPD. RESULTS: A total 100 patients were enrolled. The mean age and smoking amounts were 69.2±8.4 years and 40.6±22.3 pack-years, respectively. Sixty-seven percent of the patients reported at least one exacerbation in the past year. The mean CAT score was 16.9±8.0. The internal consistency assessed by Cronbach's alpha was 0.85. The CAT score was positively correlated with the SGRQ score (r=0.76, p<0.0001) and each component of SGRQ: symptoms, activity and impacts; r=0.68, r=0.61, and r=0.72, respectively (all p<0.0001). These positive correlations were preserved in the different groups (r=0.86, p<0.0001 in primary care clinic group; r=0.69, p<0.0001 in hospital group). The CAT score was also positively correlated to the Medical Research Council dyspnoea scale (r=0.46, p<0.0001). CONCLUSION: The Korean version of CAT had good internal consistency and showed good correlations with SGRQ. It can be used for assessing the impacts of COPD on the patient's health including primary care setting.

Osteoporosis Patient Treatment Satisfaction Questionnaire in postmenopausal women intermittently treated with oral bisphosphonates: the BRAVO study.

The Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q) is a psychometric measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The study was a multicenter, nationwide, cross-sectional, patient-reported outcome study conducted to evaluate treatment satisfaction and quality of life using the OPSAT-Q in patients receiving oral bisphosphonate therapy. This study enrolled postmenopausal women from 43 hospitals and 112 clinics who had intermittently taken oral bisphosphonates for treatment of osteoporosis. 4,220 postmenopausal Korean women with a mean age of 65.3 years and a mean body mass index of 22.9 kg/m(2) participated in the study. All items within each subscale domain were more highly correlated with their hypothesized subscale domain relative to the other subscale domains, and all 16 items were significantly correlated with an overall composite satisfaction score (CSS). All scores showed acceptable internal consistency reliability (Cronbach's alpha >0.70, range 0.88-0.91). Comparisons of OPSAT-Q scores were made between selective subgroups of participants: monthly versus weekly administration, years of taking bisphosphonates, smoking habitus, acid-related medication and comorbid conditions. Mean OPSAT-Q subscale domains and CSS were higher for users of monthly bisphosphonates, with shorter duration, non-smokers, and non-users of acid-related medication. Mean OPSAT-Q subscale domain scores of side-effects were high for absence of comorbid conditions. The OPSAT-Q demonstrated acceptable measurement properties, including validity and reliability of subscale domains and CSS, in oriental women with postmenopausal osteoporosis. Postmenopausal women intermittently using oral bisphosphonate therapy reported increased satisfaction with monthly administration, with shorter duration, non-smokers, non-users of acid-related medication, and an absence of comorbid conditions.

Virologic response to therapy increases health-related quality of life for patients with chronic hepatitis B.

BACKGROUND & AIMS: We evaluated changes in health-related quality of life (HRQoL) in a longitudinal study of patients given antiviral therapy for chronic hepatitis B (CHB). METHODS: We analyzed changes in HRQoL reported by 2856 Korean patients with CHB who started first-line or rescue antiviral therapy from January 2007 to June 2007; the mean age of the study subjects was 43.3 years, 72% were male, 80% were positive for hepatitis B e antigen, 20% had cirrhosis, and 13% had concomitant disease. These subjects all completed the translated version of the Chronic Liver Disease Questionnaire (CLDQ) and the EuroQol-5 Dimension (EQ5D) when the study began (baseline), and at the end of a 24-week follow-up period. We analyzed changes in utility scores from baseline to 24 weeks of antiviral treatment. RESULTS: After 24 weeks of antiviral therapy, patients had significant improvements in liver function and reduced mean levels of hepatitis B virus DNA (from 6.3 to 3.9 log(10) copies/mL). Utility scores from the visual analogue scale and EQ5D improved after 24 weeks of antiviral therapy (from 0.84 ± 0.19 to 0.94 ± 0.14; P < .0001). Improved CLDQ scores were associated with virologic response (level of hepatitis B virus DNA, <4 log(10) copies/mL); scores increased from 5.21 ± 0.99 at baseline to 6.09 ± 0.72 after 24 weeks of antiviral therapy in responders, but from 5.31 ± 0.94 at baseline to 6.06 ± 0.66 in nonresponders (P = .003). CONCLUSIONS: Patients with CHB who have a virologic response to 24 weeks of antiviral therapy also have significant improvements in HRQoL, measured by EQ5D and CLDQ.

Prevalence of diabetic nephropathy in primary care type 2 diabetic patients with hypertension: data from the Korean Epidemiology Study on Hypertension III (KEY III study).

BACKGROUND: The prevalence of albuminuria is known to be higher in hypertensive compared to normotensive nondiabetic patients. In addition, systolic blood pressure (BP) is found to be an independent risk factor for albuminuria in type 2 diabetes mellitus (T2DM). Based on these findings, the prevalence of albuminuria is expected to be higher in T2DM with hypertension relative to T2DM without hypertension, but it has been largely unexplored. METHODS: Prevalence rates of microalbuminuria, macroalbuminuria and renal insufficiency (RI) were investigated among 3738 hypertensive T2DM patients from 350 nationwide primary care clinics. Independent factors associated with albuminuria and RI were also characterized. RESULTS: Clinical and laboratory data of 3712 patients were included in the analysis. BP was controlled in only 1164 patients (31.4%). There were 2595 normoalbuminuric patients (70.6%), and microalbuminuria and macroalbuminuria were present in 850 (23.1%) and 230 (6.3%), respectively. The prevalence of RI was 32.1% based on estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease formula. Systolic BP correlated significantly with the natural logarithmic values of urinary albumin-to-creatinine ratio (ACR) (R = 0.16, P < 0.0001). Multivariate logistic regression analysis revealed that male sex, the duration of diabetes, systolic BP, glycated hemoglobin and eGFR were significant independent factors associated with the presence of albuminuria, while advanced age, female sex, the duration of diabetes and urinary ACR were significant independent risk factors for RI. CONCLUSIONS: A significant proportion of T2DM patients with hypertension had albuminuria and RI, and the duration of diabetes mellitus rather than the duration of hypertension was a significant independent factor associated with albuminuria and RI.

Comparison of monthly ibandronate versus weekly risedronate in preference, convenience, and bone turnover markers in Korean postmenopausal osteoporotic women.

Patient preferences, convenience, and bone turnover markers were evaluated for the monthly ibandronate over the weekly risedronate regimen in Korean postmenopausal osteoporotic women. This was a 6-month, prospective, randomized, open-label, multicenter study with a two-period and two-sequence crossover treatment design. After a 30-day screening period, eligible participants with postmenopausal osteoporosis were randomized to receive either monthly oral ibandronate 150 mg for 3 months followed by weekly oral risedronate 35 mg for 12 weeks (sequence A) or the same regimen in reverse order (sequence B). Patient preference and convenience were evaluated by questionnaire. The changes in serum C-telopeptide after 3 months of treatment were analyzed. A total of 365 patients were enrolled in this study (sequence A 182, sequence B 183). Of patients expressing a preference (83.4%), 74.8% preferred the monthly ibandronate regimen over the weekly regimen (25.2%). More women stated that the monthly ibandronate regimen was more convenient (84.2%) than the weekly regimen (15.8%). There was no significant difference in the change in bone turnover marker between the two treatments. The two regimens were similarly tolerable. There were fewer adverse events in the monthly ibandronate group compared to the weekly risedronate group in terms of gastrointestinal side effects (nausea and abdominal distension). This study revealed a strong preference and convenience for monthly ibandronate over weekly risedronate in Korean postmenopausal osteoporotic women. There was no significant difference in change of bone turnover marker and safety profile between the two regimens.

Rash in adult patients receiving lamotrigine to treat bipolar I disorder in Korea: a multicenter, prospective, naturalistic, open-label trial.

The goal of this study was to assess the incidence of rash occurring in patients received lamotrigine to treat bipolar I disorder in a real world setting in Korea. We included a heterogeneous sample with multiple medications and medical comorbidities. Lamotrigine was added to the current therapy regime for DSM-IV bipolar I patients on an open-label basis for 12 weeks. The incidences of rash and other adverse events were assessed. The primary outcome measure was the incidence of rash. A total of 237 adult patients were included in the present study and 173 patients (73.0%) completed the 12 weeks of treatment. Thirty patients (12.7%) developed a rash, of whom 2 (0.8%) developed a serious rash. There were no patients who developed Stevens-Johnson syndrome or toxic epidermal necrolysis. The median time of rash onset was 16 days. As a group, patients who did not experience rash were significantly heavier than those who did. Our findings suggest that the incidence of serious rash associated with lamotrigine is low. The prescription of lamotrigine should be undertaken with appropriate consideration of the potential risk of adverse events including rash to the patient in relation to potential benefit from improvement of bipolar disorder.