scholarly journals Efficacy of a single oral dose artesunate plus sulfalene/pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni in Kenyan children: randomised, exploratory, open-label trial

2020 ◽  
Author(s):  
Erick M.O Muok ◽  
Vincent O. Were ◽  
Charles O. Obonyo
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Cure Rate ◽  
Open Label ◽  
Serious Adverse Event ◽  
Western Kenya ◽  
Potential Alternative ◽  
Periodic Administration ◽  
To Receive

Abstract Background: The global control strategy for schistosomiasis is the periodic administration of praziquantel. Schistosomes have developed reduced susceptibility to praziquantel. Artemisinin-based drug combinations are promising alternatives to praziquantel, but it is unclear whether a single dose of an artemisinin-based drug combination is as effective and safe as praziquantel. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene/pyrimethamine in the treatment of schistosomiasis. Methods: An exploratory, open-label randomized trial, was carried out in Rarieda sub-County, western Kenya to compare the efficacy of a single oral dose of artesunate plus sulfalene/pyrimethamine (12mg/kg of artesunate) to a standard single dose of praziquantel (40mg/kg) in the treatment of school children (aged 6 to 15 years) with S. mansoni infection. The primary outcomes were cure and egg reduction rates on day 28 after treatment in the per-protocol population.Results: A total of 73 S. mansoni infected children were included and randomized to receive either artesunate plus sulfalene/pyrimethamine (n=39) or praziquantel (n=34). 67 children completed the study. The cure rate was 69.4% (25/36) in the artesunate plus sulfalene/pyrimethamine group and 80.6% (25/31) in the praziquantel group (p=0.294). Egg reduction rates were 96.2% in the artesunate plus sulfalene/pyrimethamine group and 82.9% in the praziquantel group (p=0.339). Ten children treated with praziquantel developed adverse events compared with four in the artesunate plus sulfalene/pyrimethamine group. There was no serious adverse event. Conclusion: A single oral dose of artesunate plus sulfalene/pyrimethamine was safe and as efficacious as praziquantel in the treatment of S. mansoni in Kenyan children. These results should be confirmed in larger randomized controlled trials. Combination treatment with praziquantel plus artemisinin-based combination therapies may be a potential alternative for improving praziquantel efficacy and transmission control. Trial Registration: ClinicalTrials.gov, number NCT01054651.

scholarly journals P291 Pharmacokinetics, safety, and tolerability of etrasimod (APD334) in subjects with mild, moderate, or severe hepatic impairment: a single-dose, open-label, parallel-group study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S321-S322
Author(s):  
C Lee ◽  
Y Tang ◽  
C Schroeder ◽  
J Zhang ◽  
T Nguyen-Cleary ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Normal Control ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Control Groups ◽  
Severe Hepatic Impairment ◽  
Open Label ◽  
Mean Values

Abstract Background Etrasimod is an oral, selective sphingosine 1-phosphate receptor modulator in clinical development for immune-mediated inflammatory disorders, including ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis. The objective of this study was to evaluate the effect of hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of etrasimod. Methods This single-dose, open-label, parallel-group study included 36 adult subjects (aged 18-80 years; body mass index ≥18 kg/m2) with hepatic impairment, based on Child-Pugh score at screening (mild=5 to 6 [n=8], moderate=7 to 9 [n=8], severe=10 to 14 [n=6]), and their demographically matched control subjects with normal hepatic function (n=14 total). The first subject with severe hepatic impairment was enrolled after ≥2 subjects with mild and ≥2 subjects with moderate hepatic impairment had been enrolled and followed for ≥48 hours after dosing to ensure no observed significant safety signals. On Day 1, subjects received a single oral dose of etrasimod 2 mg after a ≥10 hour fast. PK and safety data were collected over a 21-day follow-up period. Results Thirty-six subjects were enrolled and dosed; 35 subjects completed the study. When compared with their respective demographically matched normal control groups, single dose etrasimod peak exposure (Cmax) was comparable for all hepatic impairment groups, whereas etrasimod total exposure (AUC) measures were progressively higher (up to 57.3% higher) in the mild, moderate, and severe hepatic impairment groups (Table 1). Unbound etrasimod Cmax values were progressively lower (up to 42.0% lower) in the mild, moderate, and severe hepatic impairment groups, whereas unbound etrasimod AUC values were typically comparable for all hepatic impairment groups, when compared with their respective demographically matched normal control groups (Table 2). Etrasimod t1/2 only moderately increased as hepatic function decreased, with mean values ranging from 43.9 to 59.5 hours in the demographically matched normal control groups and mean values of 55.7, 69.7, and 76.5 hours in the mild, moderate, and severe hepatic impairment groups, respectively. A single oral dose of etrasimod 2 mg was well tolerated; there were no clinically significant safety findings when administered to subjects with normal hepatic function or subjects with mild, moderate, or severe hepatic impairment. Conclusion A single oral dose of etrasimod 2 mg was well tolerated, with relatively modest changes in etrasimod exposure observed in subjects with mild, moderate, or severe hepatic impairment. These results suggest that etrasimod dose adjustment may not be warranted in subjects with hepatic impairment.

scholarly journals Pharmacokinetics and Bioequivalence Study of Two Ciprofloxacin Hydrochloride Tablets in Chinese Healthy Volunteers Under Fasting and Fed Conditions: A Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period, Single-Dose Crossover Study.

2020 ◽  
Author(s):  
Fei Qin ◽  
Gan-Mi Wang ◽  
Jin-Ying Huang ◽  
Jia-Rong Wu ◽  
Wen-Jie Song ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Time Curve ◽  
Ciprofloxacin Hydrochloride ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Abstract BackgroundCiprofloxacin is a broad-spectrum fluoroquinolone antibiotic which is active against a wide range of Gram-positive and Gram-negative bacteria. The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under the fasting and fed conditions.MethodsThe study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg of ciprofloxacin hydrochloride. Blood samples were collected from an hour before dosing to 36 h after administration with 16 time points in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including maximum concentration (Cmax), area under the plasma concentration–time curve from time 0 to time t (AUC0-t), area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞). Two formulations are considered bioequivalent if the 90% confidence intervals (CIs) for the test/reference geometric mean ratios (GMRs) for the ln-transformed pharmacokinetic parameters fall within the standard acceptance range of 80% – 125%. ResultsIn total of 48 subjects were enrolled in the fasting and fed studies, and one of the subjects was excluded before the administration. In the fasting study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 85.41% to 100.97%, 95.40% to 100.27%, and 95.48% to 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 90.15% to 113.75%, 99.10% to 103.77% and 99.11% to 103.80%, respectively. A total of 8 of 47 subjects experienced AEs in the fasting and fed studies.ConclusionsIn the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after a single oral dose administration under the fasting and fed conditions. Both two brands of ciprofloxacin tablets were safe and well tolerated.Trial registrationThe clinical trial was registered at Center for the Drug Evaluation of the National Medical Products Administration (registration number: CTR20171152; date of registration：September 25, 2017; http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml).

scholarly journals Pharmacokinetic Interactions between Primaquine and Chloroquine

2014 ◽  
Vol 58 (6) ◽  
pp. 3354-3359 ◽  
Author(s):  
Sasithon Pukrittayakamee ◽  
Joel Tarning ◽  
Podjanee Jittamala ◽  
Prakaykaew Charunwatthana ◽  
Saranath Lawpoolsri ◽  
...  
Keyword(s):  
Oral Dose ◽  
Hospital Admissions ◽  
Geometric Mean ◽  
Pharmacokinetic Interaction ◽  
Plasmodium Ovale ◽  
Open Label ◽  
Content Type ◽  
Reference Number ◽  
Electrocardiographic Changes ◽  
To Receive

ABSTRACTChloroquine combined with primaquine has been the standard radical curative regimen forPlasmodium vivaxandPlasmodium ovalemalaria for over half a century. In an open-label crossover pharmacokinetic study, 16 healthy volunteers (4 males and 12 females) aged 20 to 47 years were randomized into two groups of three sequential hospital admissions to receive a single oral dose of 30 mg (base) primaquine, 600 mg (base) chloroquine, and the two drugs together. The coadministration of the two drugs did not affect chloroquine or desethylchloroquine pharmacokinetics but increased plasma primaquine concentrations significantly (P≤ 0.005); the geometric mean (90% confidence interval [CI]) increases were 63% (47 to 81%) in maximum concentration and 24% (13 to 35%) in total exposure. There were also corresponding increases in plasma carboxyprimaquine concentrations (P≤ 0.020). There were no significant electrocardiographic changes following primaquine administration, but there was slight corrected QT (QTc) (Fridericia) interval lengthening following chloroquine administration (median [range] = 6.32 [−1.45 to 12.3] ms;P< 0.001), which was not affected by the addition of primaquine (5.58 [1.74 to 11.4] ms;P= 0.642). This pharmacokinetic interaction may explain previous observations of synergy in preventingP. vivaxrelapse. This trial was registered at ClinicalTrials.gov under reference number NCT01218932.

scholarly journals Efficacy and Tolerance of Single-dose Azithromycin for Treatment of Chlamydial Cervicitis During Pregnancy

1995 ◽  
Vol 3 (5) ◽  
pp. 189-192 ◽  
Author(s):  
Joseph M. Miller
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Oral Dose ◽  
Pregnant Women ◽  
Retrospective Review ◽  
Cure Rate ◽  
Dose Oral ◽  
Oral Azithromycin

Objective: The intent of this study was to determine the efficacy and tolerance of single-dose oral azithromycin in the treatment of pregnant women with endocervical chlamydial carriage.Methods: A retrospective review of clinic records over a two-year period identified pregnant patients treated with a single 1-g dose of azithromycin for chlamydial carriage. The side effects and subsequent chlamydial carriage (test of cure) were noted.Results: A total of 146 pregnant women treated with azithromycin was reviewed. A cure rate of 96% was found. Side effects were reported in 5%.Conclusions: A single 1-g oral dose of azithromycin is effective for the treatment of chlamydia and is well tolerated in pregnant women.

scholarly journals Absolute Bioavailability of Esaxerenone and Food Effects on its Pharmacokinetics After a Single Oral Dose in Healthy Japanese Subjects: An Open-Label Crossover Study

2019 ◽  
Vol 36 (7) ◽  
pp. 1618-1627 ◽  
Author(s):  
Akifumi Kurata ◽  
Hidetoshi Furuie ◽  
Tomoko Ishizuka ◽  
Takafumi Nakatsu ◽  
Takako Shimizu ◽  
...  
Keyword(s):  
Oral Dose ◽  
Crossover Study ◽  
Single Oral Dose ◽  
Absolute Bioavailability ◽  
Food Effects ◽  
Open Label ◽  
Japanese Subjects

Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 211-211
Author(s):  
Lee Steven Schwartzberg ◽  
Richard J. Gralla ◽  
Kimia Kashef ◽  
Hope Rugo
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Complete Response ◽  
Control Group ◽  
Double Blind ◽  
Report Data ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Significant Nausea

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]

Single-Dose Therapy of Anogenital and Pharyngeal Gonorrhoea with Ciprofloxacin

1992 ◽  
Vol 3 (1) ◽  
pp. 49-51 ◽  
Author(s):  
T Balachandran ◽  
A P Roberts ◽  
B A Evans ◽  
B S Azadian
Keyword(s):  
Adverse Reaction ◽  
Single Dose ◽  
Oral Dose ◽  
Neisseria Gonorrhoeae ◽  
Treatment Failure ◽  
Single Oral Dose ◽  
Open Study ◽  
Dose Therapy ◽  
Single Dose Therapy

A single dose of ciprofloxacin, 250 mg by mouth, was used in an open study to treat pharyngeal or rectal gonorrhoea or both in 64 patients (32 men and 32 women). The study also included 151 men with urethral gonorrhoea and 53 women with cervical or urethral gonorrhoea. Ciprofloxacin cured 63 (98%) patients with pharyngeal or rectal gonorrhoea (including 5 patients with penicillinase-producing Neisseria gonorrhoeae; PPNG), 147 (97%) men with urethral gonorrhoea (including 8 with PPNG) and 52 (98%) women with cervical or urethral gonorrhoea. All the isolates of N. gonorrhoeae were sensitive to 0.03 mg/l of ciprofloxacin. Five of the 6 patients with treatment failure were subsequently cured by a single oral dose of ciprofloxacin 250 mg. None of the patients reported an adverse reaction. Ciprofloxacin 250 mg as a single oral dose is effective and safe in treating patients with pharyngeal or rectal gonorrhoea, including those with PPNG strains.

scholarly journals Quadrivalent Meningococcal Vaccination of Adults: Phase III Comparison of an Investigational Conjugate Vaccine, MenACWY-CRM, with the Licensed Vaccine, Menactra

2009 ◽  
Vol 16 (12) ◽  
pp. 1810-1815 ◽  
Author(s):  
Keith S. Reisinger ◽  
Roger Baxter ◽  
Stanley L. Block ◽  
Jina Shah ◽  
Lisa Bedell ◽  
...  
Keyword(s):  
Single Dose ◽  
Conjugate Vaccine ◽  
Geometric Mean ◽  
Case Fatality ◽  
The United States ◽  
Phase Iii ◽  
Serum Samples ◽  
Serious Adverse Event ◽  
Specific Serum ◽  
To Receive

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals ≥15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM197 conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of ≥1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than −10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

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