scholarly journals Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age

2008 ◽  
Vol 53 (3) ◽  
pp. 869-875 ◽  
Author(s):  
Xavier Sáez-Llorens ◽  
Mercedes Macias ◽  
Padmanabha Maiya ◽  
Juan Pineros ◽  
Hasan S. Jafri ◽  
...  
Keyword(s):  
Adverse Events ◽  
Plasma Levels ◽  
High Performance ◽  
Neonatal Intensive Care ◽  
Geometric Mean ◽  
Safety Data ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Young Infants ◽  
Number Of Patients

ABSTRACT Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m2 once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C 1 h) and trough (C 24 h) caspofungin levels were 8.2 and 1.8 μg/ml, respectively, on day 1, and 11.1 and 2.4 μg/ml, respectively, on day 4. GM ratios for C 1 h and C 24 h for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m2 once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.

scholarly journals Pharmacokinetics and Safety of Caspofungin in Older Infants and Toddlers

2008 ◽  
Vol 53 (4) ◽  
pp. 1450-1456 ◽  
Author(s):  
Michael Neely ◽  
Hasan S. Jafri ◽  
Nita Seibel ◽  
Katherine Knapp ◽  
Peter C. Adamson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Peak Concentration ◽  
High Performance ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Efficacy And Safety ◽  
Infants And Toddlers ◽  
Dosing Regimen ◽  
Elimination Phase ◽  
Once Daily

ABSTRACT Although information about the efficacy and safety experience with caspofungin at 50 mg/m2 daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m2 once daily in nine patients 10 to 22 months (median, 13 months) of age with fever and neutropenia who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma caspofungin concentrations were measured by high-performance liquid chromatography assay on days 1 and 4. On day 4, the area under the curve from 0 to 24 h (AUC0-24) was 130.3 μg-h/ml, the peak concentration (C 1) was 17.2 μg/ml, and the trough concentration (C 24) was 1.6 μg/ml. The day 4 geometric mean ratios (GMRs) and 90% confidence interval (CI) for these parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83 (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11 years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85, 1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase t 1/2 in infants/toddlers (8.8 h) was reduced ∼33% relative to adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse events occurred in seven patients (78%); none were considered drug related. Laboratory adverse events occurred in five patients (56%) and were considered drug related in three (33%). There were no infusion-related events or discontinuations due to toxicity. Caspofungin at 50 mg/m2 daily was well tolerated in infants and toddlers; the AUC and caspofungin C 24 were generally comparable to those in adults receiving caspofungin at 50 mg daily.

scholarly journals A Single- and Multiple-Dose Study to Characterize the Pharmacokinetics, Safety, and Tolerability of Imipenem and Relebactam in Healthy Chinese Participants

2020 ◽  
Author(s):  
Xiaohong Wang ◽  
Na Liu ◽  
Yudong Wei ◽  
Shuang Zhang ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Geometric Mean ◽  
Safety Data ◽  
Chinese Patients ◽  
Pharmacokinetic Parameters ◽  
Dependent Manner ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Multiple Doses ◽  
Healthy Chinese

Relebactam/imipenem/cilastatin is approved in the US to treat complicated urinary tract and intra-abdominal infections in patients that have limited or no alternative treatment options and HABP/VABP. Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concentration (relebactam 125, 250, or 500 mg/cilastatin 250, 500, or 1000 mg/imipenem 250, 500, or 1000 mg) and after multiple doses every 6 h of a single concentration (relebactam 250 mg/cilastatin 500 mg/imipenem 500 mg) for 14 days. After single doses, area under the concentration–time curve (AUC) extrapolated to infinity (relebactam, 15.0–70.7 h*mg/liter; imipenem, 24.1–109.8 h*mg/liter; cilastatin, 18.4–95.3 h*mg/liter) and AUC from 0–6 h (relebactam, 14.2–66.3 h*mg/liter; imipenem, 23.4–107.3 h*mg/liter; cilastatin, 18.3–94.4 h*mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9–8.3 liters/h; imipenem, 8.6–10.4 liters/h; cilastatin, 10.5–13.6 liters/h) and half-life (relebactam, 1.4–1.6 h; imipenem, 1.0–1.2 h; cilastatin, 0.7–1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8–1.0 for all three agents). Relebactam/imipenem/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

scholarly journals 1288. Phase 1 First-in-Human Single- and Multiple-Ascending Dose Trial Demonstrates Pharmacokinetics (PK) and Tolerability of SPR720, an Oral DNA GyrB Inhibitor for Mycobacterial Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
Angela Talley ◽  
Archie Thurston ◽  
Grayson Moore ◽  
Myriah M Satterfield ◽  
Erika L Manyak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Volunteers ◽  
Controlled Trial ◽  
Phase 1 ◽  
Safety Data ◽  
Elderly Subjects ◽  
Independent Contractor ◽  
Serious Adverse Events ◽  
Healthy Elderly ◽  
Dose Proportional

Abstract Background SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial lung disease (NTM-LD) and pulmonary tuberculosis. SPR719 has broad-spectrum activity versus clinically relevant mycobacteria in vitro and in murine and hollow fiber (HF) infection models. In this first-in-human single ascending dose (SAD) /multiple ascending dose (MAD) study, the safety, tolerability and pharmacokinetics (PK) of SPR720/SPR719 were evaluated in healthy volunteers. Methods This was a Phase 1 randomized, double-blind, placebo-controlled trial with 7 SAD cohorts (including a food effect cohort) and 5 MAD cohorts. Healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 or placebo in single oral doses of ranging from 100 mg to 2000 mg or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. Safety monitoring and PK sampling occurred throughout the trial. Plasma and urine concentrations of SPR720/SPR719 were measured by validated LC-MS/MS methods. PK parameters were calculated using non-compartmental analysis. Results A total of 96 subjects (including 8 healthy elderly subjects, age ≥ 65 years) were randomized and received study drug. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. Across SAD cohorts, a dose proportional and greater-than-dose proportional increase in SPR719 plasma Cmax and AUC0-24, respectively were observed. SPR720 was rapidly absorbed with a mean SPR719 t1/2 of 2.9-4.5 h. Dosing with food decreased SPR719 plasma AUC by ~20%. No clinically meaningful effect of age on plasma AUC was observed. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Day 1 and Day 7, suggesting induction of an elimination pathway. However, plasma AUC0-24 was similar at Days 7 and 14. Conclusion Together with HF pharmacodynamic data, human PK and safety data for SPR720 suggest that predicted therapeutic exposures can be attained with a well-tolerated once-daily dose. Further evaluation in a Phase 2 NTM-LD trial is planned. Disclosures Angela Talley, MD, Spero Therapeutics (Employee, Shareholder) Archie Thurston, Jr., PhD, Spero Therapeutics (Consultant) Grayson Moore, BA, RN, Spero Therapeutics, Inc. (Shareholder, Independent Contractor) Vipul Kumar, PhD, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Aaron Dane, MSc, Spero theraputics (Consultant) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee)

scholarly journals Clinical Outcomes of Digital Cholangioscopy-Guided Procedures for the Diagnosis of Biliary Strictures and Treatment of Difficult Bile Duct Stones: A Single-Center Large Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1638
Author(s):  
Hirohito Minami ◽  
Shuntaro Mukai ◽  
Atsushi Sofuni ◽  
Takayoshi Tsuchiya ◽  
Kentaro Ishii ◽  
...  
Keyword(s):  
Bile Duct ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Significant Risk ◽  
Histopathological Analysis ◽  
Bile Duct Stones ◽  
Serious Adverse Events ◽  
Visualization System ◽  
Visual Impression ◽  
Number Of Patients

Although Spy DS (SpyGlass DS Direct Visualization System) is considered to be useful for the diagnosis of bile duct strictures and the treatment of bile duct stones, there is limited data to date validating its efficacy. We hence retrospectively evaluated the clinical outcomes of the use of Spy DS in a large number of patients. A total of 183 patients who underwent Spy DS-guided procedures for indeterminate bile duct strictures (n = 93) and bile duct stones (n = 90) were analyzed retrospectively. All patients (93/93) with bile duct strictures successfully underwent visual observation, and 95.7% (89/93) of these patients successfully underwent direct biopsy. The sensitivity, specificity, and overall accuracy were 94.7%, 83.3%, and 90.3%, respectively, for visual impression; 80.9%, 100%, and 89.2%, respectively, for histopathological analysis of a direct biopsy; and 96.5%, 91.7%, and 94.6%, respectively, for visual impression combined with biopsy. Successful visualization of the stones was achieved in 98.9% (89/90) of the patients, and complete stone removal was achieved in 92.2% (83/90) of the patients, with an average of 3.3 procedures. The adverse events rate was 17.5% (32/183; cholangitis in 15 patients, fever the following day in 25, pancreatitis in 1, hemorrhage in 1, and gastrointestinal perforation in 1). No administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p < 0.01). Spy DS-guided procedures are effective for the diagnosis and treatment of bile duct lesions and can be performed with a low risk of serious adverse events.

scholarly journals 5α-Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 70 (2) ◽  
Author(s):  
Jennifer E J Jun ◽  
Angus Kinkade ◽  
Anthony C H Tung ◽  
Aaron M Tejani
Keyword(s):  
Adverse Events ◽  
Latin American ◽  
Acute Urinary Retention ◽  
Health Sciences ◽  
Prostatic Hyperplasia ◽  
Controlled Trials ◽  
Serious Adverse Events ◽  
Rétention Urinaire ◽  
Number Of Patients ◽  
Latin American And Caribbean

<p><strong>ABSTRACT</strong></p><p><strong>Background:</strong> Finasteride and dutasteride are competitive inhibitors of 5a-reductase enzymes and are commonly used to treat symptomatic benign prostatic hyperplasia (BPH).</p><p><strong>Objective:</strong> To compare the efficacy and safety of finasteride and dutasteride in terms of clinically important outcomes.</p><p><strong>Data Sources:</strong> A literature search was performed using the search terms “prostatic hyperplasia”, “prostatic hypertrophy”, “dutasteride”, “finasteride”, “quality of life”, “adverse drug reaction”, and “mortality”. The Embase, PubMed, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature databases were searched from inception to December 2015.</p><p><strong>Study Selection and Data Extraction:</strong> Randomized controlled trials, quasi-randomized trials, and systematic reviews comparing finasteride with dutasteride, either as monotherapy or in combination with a-blockers, for treatment of men with BPH were included. The outcomes of interest included need for prostate-related surgery, episodes of acute urinary retention, withdrawals due to adverse events, number of patients experiencing serious adverse events, mortality, and sexual dysfunction.</p><p><strong>Data Synthesis:</strong> Four studies involving a total of 1879 patients were included in the analysis. There were no significant differences in any of the clinically important outcomes examined: for prostate-related surgery, odds ratio (OR) 2.01 (95% confidence interval [CI] 0.18–22.24); for episodes of acute urinary retention, OR 1.47 (95% CI 0.68–3.19); for number of withdrawals due to adverse events, OR 1.10 (95% CI 0.68–1.75); for total number of patients experiencing adverse events, OR 0.94 (95% CI 0.78–1.14); for number of patients experiencing serious adverse events, OR 1.31 (95% CI 0.87–1.97); and for sexual dysfunction, OR 0.83 (95% CI 0.64–1.08).</p><p><strong>Conclusion:</strong> There is insufficient evidence to suggest that either finasteride or dutasteride offers an advantage in efficacy or safety over the other, in terms of clinically important outcomes.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte :</strong> Le finastéride et le dutastéride sont des inhibiteurs compétitifs de l’enzyme 5 alpha-réductase. Ils sont fréquemment employés comme traitement symptomatique de l’hyperplasie bénigne de la prostate (HBP).</p><p><strong>Objectif :</strong> Comparer l’efficacité et l’innocuité du finastéride et du dutastéride en ce qui concerne les résultats thérapeutiques cliniquement importants.</p><p><strong>Sources des données :</strong> Une recherche documentaire a été effectuée à l’aide des termes « hyperplasie de la prostate », « hypertrophie de la prostate », « dutastéride », « finastéride », « qualité de vie », « réaction indésirable aux médicaments » et « mortalité ». Les bases de données Embase, PubMed, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature et Latin American and Caribbean Health Sciences Literature ainsi que le Registre central Cochrane des essais comparatifs ont été interrogées pour la période allant de leur création à décembre 2015.</p><p><strong>Sélection des études et extraction des données :</strong> Les essais comparatifs à répartition aléatoire, les essais quasi-aléatoires et les analyses systématiques qui comparent le finastéride et le dutastéride, en monothérapie ou en association avec des a-bloquants, pour le traitement de la HBP chez l’homme, ont été retenus. Parmi les résultats d’intérêt, on comptait : la nécessité de recourir à une chirurgie de la prostate, les épisodes de rétention urinaire aiguë, les retraits de l’étude pour cause d’événements indésirables, le nombre total de patients ayant subi des événements indésirables graves, la mortalité et le dysfonctionnement sexuel.</p><p><strong>Synthèse des données :</strong> Quatre études comptant au total 1879 patients ont été retenues pour l’analyse. Aucune différence significative n’a été relevée en ce qui touche les résultats thérapeutiques cliniquement importants : la nécessité de recourir à une chirurgie de la prostate (risque relatif approché [RRA] de 2,01, intervalle de confiance [IC] à 95 % de 0,18 à 22,24), les épisodes de rétention urinaire aiguë (RRA de 1,47, IC à 95 % de 0,68 à 3,19), le nombre de retraits de l’étude pour cause d’événements indésirables (RRA de 1,10, IC à 95 % de 0,68 à 1,75), le nombre total de patients ayant subi des événements indésirables (RRA de 0,94, IC à 95 % de 0,78 à 1,14); le nombre de patients ayant subi des événements indésirables graves (RRA de 1,31, IC à 95 % de 0,87 à 1,97) et le dysfonctionnement sexuel (RRA de 0,83, IC à 95 % de 0,64 à 1,08).</p><p><strong>Conclusion :</strong> Il n’y a pas suffisamment de données probantes pour croire que le finastéride ou le dutastéride offrent, l’un par rapport à l’autre, un avantage quant à l’efficacité ou à l’innocuité, en ce qui concerne les résultats thérapeutiques cliniquement importants.</p>

scholarly journals Drug Interactions Between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine

2018 ◽  
Author(s):  
Stephen I Walimbwa ◽  
Mohammed Lamorde ◽  
Catriona Waitt ◽  
Julian Kaboggoza ◽  
Laura Else ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Sub Saharan Africa ◽  
Pharmacokinetic Studies ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Once Daily ◽  
Trough Concentrations ◽  
Sub Saharan

ABSTRACTAcross sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artmether-lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artmether-lumefantrine or artesunate-amodiaquine and DTG. The DTG/artmether-lumefantrine interaction was evaluated in a two-way cross-over study and measured artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DBL) over 264h. The DTG/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine (DEAQ) and measured artesunate (ARS), amodiaquine (AQ), DEAQ over 624h. Non-compartmental analysis was performed, and geometric mean ratios and 90% confidence intervals generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, time to maximum concentration and area under the concentration-time curve (AUC) for ARM, DHA, LF and DBL nor significantly alter AUC for ARS, DHA, AQ and DEAQ. Co-administration of dolutegravir with AL resulted in a 37% decrease in DTG trough concentrations. Co-administration of dolutegravir with AS-AQ resulted in a decrease of approximately 42% and 24% in DTG trough concentrations and AUC respectively. Study drugs were well-tolerated with no serious adverse events. Standard doses of artmether-lumefantrine and artesunate-amodiaquine should be used in patients receiving DTG. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and DTG exposure with artesunate-amodiaquine are unlikely to be of clinical significance as DTG trough concentrations were above DTG target concentrations of 64ng/mL.

scholarly journals Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures

2019 ◽  
Vol 35 (4) ◽  
pp. 265-273 ◽  
Author(s):  
Mark Mintz ◽  
Jesus E. Pina-Garza ◽  
Steven M. Wolf ◽  
Patricia E. McGoldrick ◽  
Sergiusz Józwiak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Safety Data ◽  
Adjunctive Treatment ◽  
Eslicarbazepine Acetate ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Focal Seizures ◽  
Clear Dose Response ◽  
Cluster Seizures

Objective: To evaluate the safety and tolerability of adjunctive eslicarbazepine acetate (ESL) in pediatric patients (aged 4-17 years) with refractory focal seizures. Methods: Pooled safety data from patients aged 4-17 years in Study 208 (NCT01527513) and Study 305 (NCT00988156) were analyzed. Both were randomized, double-blind, placebo-controlled studies of ESL as adjunctive treatment in pediatric patients with refractory focal seizures receiving 1 or 2 antiepileptic drugs. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest were evaluated. Results: The safety population comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo groups (65.6%), with no clear dose-response relationship. The most frequently reported TEAEs with ESL were headache, somnolence, vomiting, and diplopia. Overall incidences of SAEs and TEAEs leading to discontinuation were higher with ESL versus placebo (9.9% vs 5.0% and 5.9% vs 2.5%, respectively). The majority of SAEs with ESL occurred in Study 305. Two deaths were reported, 1 with ESL (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils) and 1 with placebo (0.6%) due to asphyxia. TEAEs related to allergic reaction, hyponatremia, hypothyroidism, cytopenia, seizure exacerbation, cognitive dysfunction, psychiatric disorders, or suicide occurred infrequently (<9%). Conclusion: Adjunctive ESL was generally well tolerated in children aged 4-17 years with focal seizures. The safety profile of ESL in children was comparable to that observed in adults.

Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽  
2004 ◽  
Vol 24 (10) ◽  
pp. 888-893 ◽  
Author(s):  
H Göbel ◽  
A Heinze ◽  
U Niederberger ◽  
T Witt ◽  
V Zumbroich
Keyword(s):  
Adverse Events ◽  
Randomized Study ◽  
Controlled Study ◽  
Acute Migraine ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Number Of Patients ◽  
Significant Difference ◽  
Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

scholarly journals First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Mammen P. Mammen ◽  
Danielle Armas ◽  
Frank H. Hughes ◽  
Andrew M. Hopkins ◽  
Cindy L. Fisher ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Safety Data ◽  
Healthy Adults ◽  
Antifungal Drug ◽  
Renal Elimination ◽  
Serious Adverse Events ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Time Curve

ABSTRACT VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study, was conducted in healthy adults to determine the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (i.v.) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing cohort prior to recommending the initiation of each subsequent cohort. No serious adverse events (SAEs) occurred; the majority of treatment-emergent adverse events (TEAEs) were mild and self-limited. The most common drug-related TEAEs were infusion site reactions. No clinically concerning trends were noted in vital signs, electrocardiograms, physical examinations, or safety laboratory results. Following single infusions of VL-2397, the overall and maximum exposures rose less than proportionally with increasing doses from 3 mg to 1,200 mg as indicated by area under the concentration-time curve over 24 h (AUC24) and maximum concentration (Cmax). No signs of VL-2397 accumulation were observed following i.v. infusions of 300, 600, and 1,200 mg every 24 h (q24h) for 7 days. Renal elimination played a major role in total body clearance, with up to 47% of unmetabolized drug in urine 24 h after administration at single doses of >30 mg. Overall, VL-2397 dosing in the study appeared to be safe and well tolerated in the healthy subjects. The safety profile, consistent PK, and lack of drug accumulation support further development of VL-2397 in patients with invasive aspergillosis.

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