Study In Chinese Subjects Research Articles

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate‐to‐severe facial acne vulgaris: A phase 3, multi‐centre, randomized, double‐blind, vehicle‐controlled study

AbstractBackgroundFMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate‐to‐severe acne vulgaris (AV).ObjectiveTo evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate‐to‐severe facial AV.MethodsThis was a multi‐centre, randomized, double‐blind, vehicle‐controlled phase 3 study in Chinese subjects with moderate‐to‐severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12.ResultsIn total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (−21.0 [0.08] vs. −12.3 [1.14]; LSM [SE] difference, −8.7 [1.34]; 95% CI [−11.3, −6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (−19.4 [1.03] vs. −14.9 [1.47]; LSM [SE] difference, −4.5 [1.74]; 95% CI [−8.0, −1.1]; p = 0.009). Most treatment‐emergent adverse events (TEAEs) were mild‐to‐moderate in severity, and no treatment‐related treatment‐emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well‐tolerated product during the 12‐week treatment period.ConclusionFMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate‐to‐severe facial AV. It also showed a well acceptable safe and tolerability profile.

The place and role of Chinese themes in Russian literature of the XIX – early XX centuries

The article presents the artistic perception of Chinese culture in the Russian literature of the XIX – early XX centuries. The author sets out to show a generalized image of China in the works of Russian prose writers and poets in a given historical period of time. The relevance of the research lies in the increased interest of modern linguistic science in the problems of intercultural dialogue. It is noted that the study of Chinese subjects in Russian literature is of indisputable interest for understanding the peculiarities of intercultural communication between Russia and China. The multifaceted Chinese culture is revealed through the eyes of Russian writers of the past centuries, who were attracted by Chinese images, plots, and motives. The history of Russian-Chinese relations is traced in the mirror of advanced Russian culture of the XIX – early XX centuries. The tendency to understand China as a unique civilization distinct from the European one, which had already emerged at that time, stands out. It is stated that the substantial development of ideas about China in Russian literature, at the time interval of interest to the researcher, is directly related to the emerging socio-political situation in the Russian Empire, the emergence of alternatives, both in terms of determining the further vector of social development, taking into account the problem of "West – Russia – East", i.e. the emerging situation of internal choice, self–determination and awareness by the ruling circles of the urgent need to work out a further path for the development of Russian statehood, taking into account the borrowing, on the one hand, of the Western, on the other – of the eastern model. This, in the author's opinion, explains the interest of representatives of Russian literature in the culture of the East, spiritual and moral values, philosophical reflections on the nature of goodness and justice, which had a centuries-old tradition in China.

A Multicenter Noninferiority Study Comparing Safety and Effectiveness of Hyaluronic Acid Fillers for Correction of Nasolabial Folds in Chinese Subjects.

This was a prospective, controlled clinical study in Chinese subjects. Subjects with symmetrical moderate NLFs according to the Wrinkle Severity Rating Scale were randomized to receive BEL in one NLF and RES in the other. The primary objective was to investigate whether BEL is noninferior compared with RES after being injected mid-dermally in moderate NLFs after 6 months. Secondary objectives included responses at other visits and pain sensation. Treatment-emergent adverse events (TEAEs) were assessed. A total of 220 subjects were enrolled. The Wrinkle Severity Rating Scale response rates at month 6 were 62.9% for BEL versus 64.9% for RES, demonstrating noninferiority. The secondary endpoints supported this. Significantly reduced pain scores were observed for BEL versus RES. For both products, injection site nodule and bruising were the most frequent treatment-emergent adverse events at the injection site. All treatment-related treatment-emergent adverse events were mild. The study showed that BEL is effective and well tolerated for correction of moderate NLFs in Chinese subjects. Noninferiority of BEL was demonstrated compared with RES, and regardless of applied pain treatment, a further reduction in injection pain was observed in BEL.

Commentary on: Hyaluronic Acid Compound Filling Plus Mesotherapy vs Botulinum Toxin A for the Treatment of Horizontal Neck Lines: A Multicenter, Randomized, Evaluator-Blinded, Prospective Study in Chinese Subjects.

See the Original Article here. We read with interest the article entitled “Hyaluronic Acid Compound Filling Plus Mesotherapy vs Botulinum Toxin A for the Treatment of Horizontal Neck Lines: A Multicenter, Randomized, Evaluator-Blinded, Prospective Study in Chinese Subjects.” 1 We enjoyed reading this study, and we appreciate the opportunity to provide our comments. In this article, the authors take a novel approach to the treatment of “horizontal neck lines” that involves a combination technique for hyaluronic acid (HA) filler injection: linear threading within the horizontal rhytids, combined with intradermal field injection with mesotherapy needles. They compared the outcomes of this technique (HA filling plus mesotherapy) with targeted intradermal injection of onabotulinum toxin A (BTX-A; Botox, Allergan, Irvine, CA), and concluded that HA filling plus mesotherapy is superior. We did not find any major flaws in this study, and the authors should be commended for organizing a prospective, multicenter, randomized,...

Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide.

ObjectivesTo demonstrate the synergistic effect of 4‐hexylresorcinol (4‐HR) with niacinamide in boosting anti‐melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial.MethodsPrimary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4‐HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double‐blind, split‐face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12‐week study period.Results In vitro tyrosinase enzyme activity studies showed that 4‐HR is one of the most potent tyrosinase inhibitors. The combination of 4‐HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4‐HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product‐related adverse events.ConclusionsA formulation containing a combination of 4‐HR and niacinamide delivered superior skin tone and anti‐ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.

Determination of thiorphan, a racecadotril metabolite, in human plasma by LC-MS/MS and its application to a bioequivalence study inChinese subjects .

The objective of this study was to use LC-MS/MS to compare the pharmacodynamic properties and bioequivalence of two 200-mg formulations of racecadotril: suspension formulation (test) and granule formulation (reference) in healthy Chinese subjects. A single-dose, randomized, two-period crossover study was conducted in fasted healthy Chinese subjects, who received a single oral dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. The rapid and highly sensitive LC-MS/MS method exhibited a reasonable linearity range (2.324-952.000ng/mL) and high sensitivity (LLOQ of 2.324ng/mL). The within- and between-run precision, accuracy, and stability results were within the acceptable limits, and no matrix effect was observed. The 90% CI of the ratio of geometric means for AUC0-t, AUC0-∞, and Cmax were 88.1-102.3%, 87.9-101.5% and 99.5-113%, respectively, which met the regulatory criteria for bioequivalence. The method is suitable for quantification of thiorphan in human plasma. In addition, the results indicated that the test and reference formulations were bioequivalent in terms of both rate and extent of absorption.

Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Ferric Carboxymaltose in Chinese Patients with Iron-deficiency Anemia

PurposeIron deficiency (ID) is one of the most commonly known nutritional deficiencies and is considered the primary cause of anemia (iron-deficiency anemia). Ferric carboxymaltose (FCM), an intravenous iron preparation, has been widely used for >10 years for iron-deficiency anemia treatment worldwide because of its many advantages. MethodsThis single-center, open-label, single dose escalation study in Chinese subjects was designed to assess the pharmacokinetic/pharmacodynamic parameters and safety of FCM in this population. The first 12 subjects received a 500-mg dose; after assessing safety data from the first 6 subjects in this cohort, another 12 subjects were assigned to the 1000-mg dose cohort. FindingsAfter an infusion of FCM over 15 min, a rapid dose-dependent increase in total serum iron levels was observed with a median Tmax of 30 min following the start of the infusion for both cohorts. The Cmax and AUC for the 1000-mg dose were ~1.8-fold (p = 0.2929) and 2.3-fold (p = 0.0318) those associated with the 500-mg dose, respectively. Mean terminal t1/2 values were 12.3 and 10.5 h for the 2 cohorts. The renal elimination of FCM was negligible (<0.1%). Increase in mean serum iron levels and ferritin concentrations showed dose dependency. Iron-binding capacity was transiently well utilized after dosing, as indicated by transferrin saturation >88% with 500-mg FCM and >90% with 1000-mg FCM. Hemoglobin levels did not show significant changes during the 7-day observation period, whereas mean reticulocyte counts significantly increased in both cohorts, suggesting activation of the hematopoietic system. FCM was well tolerated in these Chinese subjects. No new or unexpected treatment-emergent adverse events were attributable to FCM. ImplicationsThe pharmacokinetic/pharmacodynamic and safety profiles in Chinese subjects seemed comparable to those in white and Japanese populations. ChinaDrugTrials.org.cn identifier: CTR20160863

A proof-of-concept study to evaluate the efficacy and safety of BTI320 on post-prandial hyperglycaemia in Chinese subjects with pre-diabetes

BackgroundGalactomannan(s) are plant-derived fiber shown to reduce post-prandial blood glucose by delaying intestinal absorption of carbohydrates and slowing down gastric emptying. We examined glucose-lowering effects of BTI320, a propriety fractionated mannan(s) administered as a chewable tablet before meal in a proof-of-concept study in Chinese subjects with prediabetes.MethodsSixty Chinese adults aged 18–70 years with either impaired fasting glucose, impaired glucose tolerance, or glycated haemoglobin 5.7–6.4% (39-46 mmol/mol), were randomly assigned in 2:2:1 ratio to either BTI320 8 g (high dose), BTI320 4 g (low dose) or matching-placebo three times daily before meal for 16 weeks. The primary endpoint was change in fructosamine in subjects treated with BTI320 compared with placebo from baseline to week 4. Indices of glycaemic variability based on continuous glucose monitoring (CGM) and standard meal tolerance test were explored in secondary analyses.ResultsOf 60 subjects randomized, 3 subjects discontinued study treatment prematurely. In intention-to-treat analysis, no significant differences in change in serum fructosamine between low or high dose BTI320 and placebo were observed. Using random effect models, adjusted for variability by meals, treatment with low dose BTI320 was associated with reduction in 1-h (p < 0.01), 2-h (p = 0.01) and 3-h (p = 0.02) post-prandial incremental glucose area-under-curve and post-meal maximum glucose (p = 0.03) compared with placebo. Subjects receiving low dose BTI320 had greater body weight reduction than placebo group.ConclusionsBTI320 did not change fructosamine levels compared with placebo. BTI320 reduced glycaemic variability based on CGM indices.Trial registrationThe study was registered at www.clinicaltrials.gov, reference number NCT02358668 (9 February 2015).

Influence of APOA5 Locus on the Treatment Efficacy of Three Statins: Evidence From a Randomized Pilot Study in Chinese Subjects.

Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5, which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5–10 mg/day), atorvastatin (10–20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T > C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol, and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results suggest that future studies may need to consider stratifying subjects not only by genetic background but also by prescribed statin type.

Sex-Dependent Choroidal Thickness Differences in Healthy Adults: A Study Based on Original and Synthesized Data

ABSTRACTPurpose: The purpose of this study is to determine the influence of sex on choroidal thickness (CT) in healthy adults.Methods: Healthy Chinese adults were recruited and complete ophthalmic examinations were performed. The choroid was imaged by swept-source optical coherence tomography and the macular CT in Early Treatment Diabetic Retinopathy Study grids was obtained by the intrinsic automated segmentation software. CT in males and females was compared after controlling other factors. All of the published studies in PubMed were systemically tracked, and a syntheses analysis of the combined data of the present study and previous studies was performed to address this issue further.Results: A total of 104 healthy adults were included, of whom 38 (37%) were male and 66 (63%) were female. Older age and longer axial length (AL) each were significantly associated with thinner CT. After controlling for age and AL, the foveal CT and average macular CT were 25.5 μm (95% CI: 0.5–50.4 μm) and 22.1 μm (95% CI: 2.7–41.4 μm) thicker in men than in women, respectively. Significant differences in CT between males and females were also observed in inner and outer rings after controlling for age and AL (P < 0.05). After strict screening, 15 previously reported studies were determined to be eligible for inclusion. The combination of data collected from 2821 males and 3389 females provided further evidence that the choroid is thicker in males, with a pooled mean difference of 19.5 μm (95% CI: 11.4 to 27.6) for foveal CT and 14.7 μm (95% CI: 6.8 to 22.6) for average CT.Conclusion: Our study of Chinese subjects, along with the syntheses analysis, strengthens the evidence that CT is greater in males than in females, based on OCT measurements. This observation may be pertinent for the sex disparities in some clinical conditions related to CT.

Safety and Effectiveness of Juvéderm Ultra Plus Injectable Gel in Correcting Severe Nasolabial Folds in Chinese Subjects

Background:Hyaluronic acid dermal fillers are effective in correcting severe nasolabial folds (NLFs) in non-Asian populations. We assessed safety and effectiveness of Juvéderm Ultra Plus in a Chinese population.Methods:This double-blind study randomized Chinese subjects with severe NLFs to Juvéderm Ultra Plus (24 mg/mL) in 1 NLF and Restylane injectable gel (20 mg/mL) in the other NLF. NLFs were evaluated using the validated 5-point photonumeric Allergan NLF Severity Scale (0 is “no wrinkle” and 4 is “very deep wrinkle”). Investigator-assessed responder rates (primary outcome at 6 months), NLF mean improvements, and subject-assessed responder rates and preference were assessed.Results:Of 124 subjects randomized, 122 completed the 6-month visit. NLFs treated with Juvéderm Ultra Plus required less volume than those treated with Restylane (median [range]: 0.80 [0.3–2.0] vs 1.00 [0.3–1.9]; P<0.001). Investigator-assessed responder rates were 90.4% for Juvéderm Ultra Plus and 89.6% for Restylane, establishing noninferiority of Juvéderm Ultra Plus. Mean (SD) improvements in NLF Severity Scale scores from baseline at 6 months were 1.5 (0.75) for Juvéderm Ultra Plus and 1.6 (0.73) for Restylane. Subject-assessed responder rates were similar to investigator-assessed rates (87.3%, Juvéderm Ultra Plus; 83.9%, Restylane). Of subjects reporting a preference, 62.1% preferred Juvéderm Ultra Plus. The most common treatment site responses were swelling and tenderness; most were mild or moderate in severity and resolved without intervention. Juvéderm Ultra Plus had fewer severe treatment site responses than Restylane.Conclusion:In this study in Chinese subjects, Juvéderm Ultra Plus was safe and effective for correcting severe NLFs.

Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST

BackgroundPrior studies have demonstrated conflicting results regarding the relationship between corneal biomechanical properties and refractive error. Thus, the purpose of this study was to compare the corneal biomechanical parameters of myopes and emmetropes.MethodsNinety‐four subjects with varying degrees of myopia (aged 29 to 74-years, spherical equivalent [SE] −0.5 to −17.5 D) and 25 emmetropes (aged 19 to 75-years, SE: −0.5 to +0.5 D) presenting at the Queen Mary Hospital, Hong Kong were recruited sequentially for this prospective study. All patients were phakic with no history of coexisting ocular disease. The corneal biomechanical parameters of the right eye of each subject were analysed using the Corvis ST non‐contact tonometer. Intraocular pressure (IOP) was measured using both the Corvis ST and the Topcon Non‐Contact Tonometer CT‐80. Refractive error was measured by non‐cycloplegic subjective and objective refractometry.ResultsHigh myopes (SE greater than −6.00 D) demonstrated greater mean outward applanation velocities (p < 0.001) and peak distance measurements (p = 0.009) compared to both low to moderate myopes (SE −0.50 to −6.00 D) and emmetropes. Both outward applanation velocity and peak distance were moderately correlated with refractive error (p ≤ 0.001), strongly correlated with IOP and weakly correlated with central corneal thickness. There were no statistically significant differences in age, IOP or central corneal thickness among emmetropes, low to moderate myopes or high myopes.ConclusionWithin this study of Chinese subjects, high myopes demonstrate greater corneal mean outward applanation velocity on Corvis ST testing, than emmetropes. In particular, those with high myopia (SE greater than −6.00 D) show a distinct corneal biomechanical profile relative to those with either emmetropia or low to moderate myopia using the Corvis ST.

Investigation of optimal aminolaevulinic acid concentration applied in topical aminolaevulinic acid-photodynamic therapy for treatment of moderate to severe acne: a pilot study in Chinese subjects

Aminolaevulinic acid-photodynamic therapy (ALA-PDT) is a novel and effective treatment in acne. However, little is known about the effect of different concentrations of ALA in the treatment of acne in Chinese patients with Fitzpatrick skin type III and IV. To investigate the efficacy and safety of ALA-PDT in the treatment of moderate to severe acne in Chinese patients and to identify the suitable concentration of topical ALA. One hundred and eighty patients with moderate to severe facial acne were recruited and randomly divided into four groups. Each group was treated with a different concentration (5%, 10%, 15% and 20%) of ALA to the facial lesions on the right side and placebo agent on the left side as control. Each patient was treated once every 10 days for four sessions. The numbers of inflammatory and noninflammatory acne lesions were counted at baseline and at weeks 2, 4, 12 and 24 after the last treatment. Adverse effects were recorded at each follow-up visit. After 24 weeks, each side treated by ALA-PDT showed clinical improvement compared with the control side treated by red light alone (P < 0·01). Statistically significantly more patients treated with 20% ALA than with 15% or 10% ALA achieved complete clearance. Regarding side-effects, a trend towards more serious erythema and pigmentation was observed with increasing ALA concentration. Increasing the concentration of ALA seems to be beneficial for improving the results. Considering effectiveness and safety, ALA-PDT using 10% or 15% ALA is suggested to the ideal treatment for moderate to severe acne in Chinese patients with Fitzpatrick skin type III and IV.

Lack of association between human G-protein beta3 subunit variant and overweight in Japanese workers.

We examined the association of the G-protein beta3 subunit gene (GNB3) C825T polymorphism with overweight in Japanese workers. This cross-sectional study used multivariate analysis to investigate whether a polymorphism in the C825T polymorphism was associated independently with overweight when factors such as age and lifestyle were taken into account. The study in 1453 men and 1172 women involved identifying subjects with the C825T genotype using the polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Overweight was defined as a BMI > or = kg/m(2). Genotype distributions for C825T in overweight men (CC = 80, CT = 162, TT = 80) and women (CC = 52, CT = 91, TT = 40) were not significantly different from normal-weight men (CC = 278, CT = 588, TT = 265) and women (CC = 242, CT = 549, TT = 198). The allele distributions were also not significantly different between either sex. The power of the study was estimated as 98% in men and 81% in women based on the allelic frequencies reported in a previous positive study in Chinese subjects. Multiple logistic regression analysis showed that the genotype was not significantly associated with overweight. In conclusion, this study indicated that the GNB3 C825T polymorphism is not a significant factor for overweight in Japanese people.