Bioequivalence of a Generic Nateglinide Formulation in Healthy Chinese Volunteers under Fasting and Fed Conditions: A Randomized, Open-Label, Double-Cycle, Double-Crossover Study

Pharmacology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Ming Yu ◽  
Xiaobin Li ◽  
Hao Jin ◽  
Lu Chen ◽  
Nan Wang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Vital Signs ◽  
Reference Formulation ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Laboratory Test Results ◽  
Liquid Chromatography Tandem Mass ◽  
Healthy Chinese

<b><i>Introduction:</i></b> Nateglinide or <i>N</i>-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine is a drug with a rapid hypoglycemic effect that is mainly used in the treatment of type 2 diabetes. Very few studies have assessed bioequivalence based on feeding status. This study aimed to assess the pharmacokinetic bioequivalence and safety of nateglinide-containing tablets (0.12 g) in healthy Chinese volunteers under fasting and fed conditions. <b><i>Methods:</i></b> The studies were performed in 2017–2018 in the Phase I Clinical Trial Ward of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China. Eligible Chinese volunteers received a single 0.12-g dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. Blood samples were collected at various time intervals, and plasma nateglinide concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Then, the adverse events, laboratory test results, vital signs, and physical exam findings were compared between the 2 groups. <b><i>Results:</i></b> The ratios of the geometric means of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub> of the tested to reference preparations under fasting conditions were 105.03% (90% confidence interval [CI]: 99.53–110.83%), 104.02% (90% CI: 101.37–106.74%), and 104.04% (90% CI: 101.38–106.77%), respectively. The same ratios under fed conditions were 96.55% (90% CI: 85.80–108.65%), 103.08% (90% CI: 100.07–106.18%), and 103.07% (90% CI: 100.21–106.01%), respectively. The 90% CI values for C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub> fell within the accepted range of bioequivalence (80.00–125.0%). Common adverse events included hypoglycemia, heart rate increase, palpitation, sweating, dizziness, and diarrhea. <b><i>Conclusions:</i></b> The test formulation (0.12 g) met the CFDA’s regulatory definition for bioequivalence to the reference formulation. Both formulations were well tolerated by healthy Chinese subjects. <b><i>Trial Registration:</i></b> This trial has been registered in the Chinese Clinical trial registry (ChiCTR2000030694), March 10, 2020.

scholarly journals Efficacy and Safety of Tetrahydrocurcuminoids for the Treatment of Canker Sore and Gingivitis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Muhammed Majeed ◽  
Shaheen Majeed ◽  
Kalyanam Nagabhushanam
Keyword(s):  
Clinical Trial ◽  
Pain Score ◽  
Vital Signs ◽  
Analog Scale ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Chewable Tablet ◽  
Before And After ◽  
Therapeutic Activities ◽  
Clinical Trial Methods

Background. Tetrahydrocurcuminoids (THCs) are among the major metabolites of curcuminoids with a higher bioavailability and physiological stability and exhibit a broad spectrum of therapeutic activities. The objective of this study was to evaluate the efficacy of THCs in patients suffering from canker sore and gingivitis designed as an exploratory clinical trial. Methods. This is an open label prospective pilot clinical trial carried out at two clinical centers: Noble Hospital, Pune, Maharashtra, and Sri Venkateshwara Hospital, Bangalore, Karnataka in India. Participants were assigned to 21 days of treatment with chewable oral THCs supplement. Patients were instructed to self-administer one chewable tablet containing 100 mg of THCs twice daily for up to 21 days. This clinical trial was registered at a public Clinical Trial Registry in India (http://www.ctri.nic.in). Thirty-one canker sore and twenty-nine gingivitis patients participated in this study. Body mass index, throat numbness/relief, Visual Analog Scale (VAS) pain score, canker sore lesions, gingival appearance, inflammation and bleeding were assessed before and after treatment, at 14 and 21 days. Vital signs and laboratory parameters were assessed for safety. Results. THCs treatment significantly reduced the reddening at the site, difficulty in chewing, swallowing, and VAS pain score in the canker sore patients. Further, both single and multiple lesions were completely healed. In gingivitis patients, gingival appearance, bleeding, and inflammation were significantly reduced. No adverse effects were observed during the study. Conclusion. Overall, the findings of this study show that supplementation of THCs for 21 days reduced the pain and prevented the progression of the disease in patients suffering from canker sore and gingivitis without adverse side effects.

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial

2021 ◽  
Vol 30 (Sup5) ◽  
pp. S7-S14
Author(s):  
Thomas E Serena ◽  
Neal M Bullock ◽  
Windy Cole ◽  
John Lantis ◽  
Lam Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Diabetic Foot ◽  
Oxygen Therapy ◽  
Wound Closure ◽  
Foot Ulcers ◽  
Controlled Clinical Trial ◽  
Diabetic Foot Ulcers ◽  
Open Label ◽  
Number Of Patients

Objectives: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). Method: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. Results: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. Conclusion: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

Hibiscus sabdariffa tea affects diet-induced thermogenesis and subjective satiety responses in healthy men, but not in women: a randomized crossover trial

2021 ◽  
Author(s):  
Natália Cristina de Faria ◽  
Ana Paula da Costa Soares ◽  
Guilherme Fonseca Graciano ◽  
Maria Isabel Toulson Davisson Correia ◽  
Magda Carvalho Pires ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Food Intake ◽  
Energy Expenditure ◽  
Resting Energy Expenditure ◽  
Hibiscus Sabdariffa ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Satiety Response ◽  
Diet Induced Thermogenesis ◽  
Desire To Eat

The aim of this study was to investigate the effect of Hibiscus sabdariffa tea on energy expenditure, satiety response and food intake. This is an open-label, crossover, randomized clinical trial (RBR-5HZ86T), including 21 subjects (11 women, 10 men). The individuals were evaluated at acute moments (fasting and after eating standardized breakfast accompanied by water or Hibiscus sabdariffa tea). Resting energy expenditure was measured by indirect calorimetry, subjective satiety responses were evaluated with a visual analogue scale and food intake was assessed by using food records. The volunteers who drank the Hibiscus sabdariffa tea had lower perception of hunger (p=0.002) and greater feeling of satiety (p=0.010) and fullness (p=0.009) compared to control. Men who ingested the Hibiscus sabdariffa tea had an increase in nitrogen energy expenditure (water: 1501±290.7kcal, Hibiscus sabdariffa tea: 1619±288.9kcal; p=0.029). In comparison to control, men presented less perception of hunger (p=0.003) and desire to eat (p=0.016), increased satiety (p=0.021) and fullness (p=0.010), and women oxidized more fat (p=0.034) when they drank Hibiscus sabdariffa tea. There was no difference between treatments regarding the energy and macronutrient intake from the first meal and throughout the day (p>0.050) for all participants. The Hibiscus sabdariffa tea only affected energy expenditure and satiety responses in men. Clinical trial registry: ReBEC Platform of the Brazilian Clinical Trials Registry - RBR-5HZ86T Novelty bullets • Hibiscus sabdariffa tea promoted an increase in energy expenditure and caused less perception of hunger/desire to eat in men. • Hibiscus sabdariffa tea intake increased postprandial fat oxidation in women.

scholarly journals Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

2020 ◽  
Author(s):  
Miquel Pujol ◽  
José-María Miró ◽  
Evelyn Shaw ◽  
Jose-María Aguado ◽  
Rafael San-Juan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Staphylococcus Aureus ◽  
Adverse Events ◽  
Primary Endpoint ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Statistical Significance ◽  
Treatment Success ◽  
Open Label ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia

Abstract Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. Clinical Trials Registration NCT01898338.

A pilot clinical trial of p53/p16-independent epigenetic therapy for pancreatic ductal adenocarcinoma (PDA).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 699-699
Author(s):  
Davendra Sohal ◽  
Smitha S. Krishnamurthi ◽  
Rita Tohme ◽  
Dale Randall Shepard ◽  
Alok A. Khorana ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Median Time ◽  
Dna Methyltransferase ◽  
Cleveland Clinic ◽  
Ductal Adenocarcinoma ◽  
Epigenetic Therapy ◽  
University Hospitals ◽  
Open Label ◽  
Ecog Ps

699 Background: PDA treatment is limited to cytotoxic drugs. A key factor limiting their efficacy is TP53 mutations, omnipresent in PDA, which counter apoptosis-mediated cell kill. We evaluated a novel epigenetic approach using decitabine (Dec) to inhibit DNA methyltransferase 1 (DNMT1) and effect cancer cell cycle exits by epithelial-differentiation, combined with tetrahydrouridine (THU) to inhibit cytidine deaminase (CDA) and thereby permit oral bioavailability and solid-tissue distribution of Dec. Methods: Open-label single-arm, IRB-approved clinical trial at Cleveland Clinic and University Hospitals for patients with metastatic PDA that had progressed on prior chemotherapy, ECOG PS of 0-2. Treatment was oral, weight-based, with Dec 10-20 mg, and THU 500-1000 mg daily, 5 days/week. Primary endpoint was DNMT1 protein levels at 16-week vs baseline biopsies. Results: From Apr to Aug 2017, we enrolled 13 patients. Median age was 65 (range 44-74) years; 7 (54%) males; 11 (85%) Caucasians. Median time from diagnosis was 13 (3.9-53.5) months, with a median of 2 (1-3) prior lines of therapy. Baseline ECOG PS was 0/1 in 12 (92%) patients. All patients started study drugs; median time on treatment was 35 (4-63) days, and on study 72 (25-105) days. The most frequent adverse events attributable to the study drugs were anemia (n=5), and anorexia, dehydration, nausea, fatigue, febrile neutropenia and decreased lymphocyte count, in 3 patients each; no deaths. Eight (62%) patients underwent evaluation scans at 8 weeks, showing stable disease in 1 patient and progression in 7. Common reasons for coming off of study drugs were progression (n=6), physician discretion (n=3), and adverse events (n=2). Overall, 6 patients died; median survival was 3.1 months, and patients did not reach the 16-week biopsy. Shifts in blood counts, a sensitive indicator of Dec systemic activity, were unexpectedly mild, and plasma CDA enzyme activity was increased versus other cancer and normal controls. Conclusions: This first-of-its-kind study demonstrated feasibility and safety of the novel oral epigenetic therapy. Systemically elevated CDA in these patients requires higher doses of THU; a trial accordingly refined is planned. Clinical trial information: NCT02847000.

A phase I clinical trial to assess the safety, pharmacokinetics, and antitumor activity of glumetinib (SCC244) in patients with advanced non-small cell lung cancers (NSCLCs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21702-e21702
Author(s):  
Hua-Jun Chen ◽  
Jin-Ji Yang ◽  
Xuening Yang ◽  
Qing Zhou ◽  
Minghui Sun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase I ◽  
Dose Escalation ◽  
Advanced Nsclc ◽  
Clinical Activity ◽  
Maximum Plasma ◽  
Open Label ◽  
Elevated Alkaline Phosphatase ◽  
Once Daily

e21702 Background: Aberrant activation of the MET pathway is associated poor prognosis and poor response to standard therapies in cancer patients. Glumetinib (SCC224) is an oral potent and highly selective MET inhibitor. This is an open label, dose-escalation, phase I clinical study to determine the safety, pharmacokinetics and anti-tumor activity in patients with advanced NSCLC regardless of MET status. Methods: Patients with advanced NSCLC failed standard treatments received glumetinib orally according to one of four dose escalation regimens on a 28-day cycle: 100 mg, 200 mg, 300mg and 400 mg once daily, in a Pharmacologically Guided Dose Escalation (PGDE) design (a variation of the standard 3+3 design). The primary endpoints are the incidence of dose limit toxicity (DLT), maximally tolerated dose (MTD), biologically effective dose (BED). The secondary endpoints are treatment-emergent adverse events (TEAE), safety and tolerability, anti-tumor efficacy, pharmacokinetics, and its metabolites. Results: As of Feb 7, 2020, a total of eighteen eligible (18) patients were enrolled into this study: 3 at 100 mg, 3 at 200 mg, 6 at 300 mg and 6 at 400 mg. Only one patient among 6 evaluable patients at 400mg cohort reported one DLT of grade 3 vomiting. Treatment-related adverse events mostly were grade 1 or 2 nausea, vomiting, elevated alkaline phosphatase, elevated conjugated bilirubin, edema, headache, asthenia and decreased appetite. Non-DLT treatment related G3/4 adverse events were peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%). Absorption was rapid after dosing and the median time to reach maximum plasma drug concentration ( Tmax) was 2.0‐6.0 hours. The mean value of half-life(t1/2) in each dose group ranged from 20.43h to 35.36 h. In response to glumetinib, one patient with MET overexpression at 200mg dose level had a best of response of partial response and completed 44 weeks glumetinib treatment, 4 patients (3 with MET amplification) had a best of response of stable disease. Conclusions: Glumetinib was well tolerated at doses up to 400 mg once daily and demonstrated clinical activity in advanced NSCLC with MET alterations. Glumetinib is used in ongoing clinical trials to further explore safety and efficacy in NSCLC. Clinical trial information: NCT03466268.

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