Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (−2.03 ± 1.7 as compared with −0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (−1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

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Pharmacokinetics and Safety of Famciclovir in Children with Herpes Simplex or Varicella-Zoster Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01054-08 ◽

2009 ◽

Vol 53 (5) ◽

pp. 1912-1920 ◽

Cited By ~ 21

Author(s):

X. Sáez-Llorens ◽

R. Yogev ◽

A. Arguedas ◽

A. Rodriguez ◽

M. G. Spigarelli ◽

...

Keyword(s):

Herpes Simplex ◽

Varicella Zoster Virus ◽

Multiple Dose ◽

Systemic Exposure ◽

Varicella Zoster Virus Infection ◽

Pharmacokinetic Data ◽

Dosing Regimen ◽

Open Label ◽

Two Phase ◽

Varicella Zoster

ABSTRACT Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (∼12.5 mg/kg of body weight [BW] for children weighing <40 kg and 500 mg for children weighing ≥40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to <6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW0.696. An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

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669. Twelve-Month Durability of Microbiota-Based Therapy RBX2660 for Prevention of Recurrent Clostridium difficile Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.737 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S306-S306

Author(s):

Courtney Jones ◽

Sarah Mische ◽

Ken Blount ◽

Bill Shannon

Keyword(s):

Clostridium Difficile ◽

Treatment Options ◽

Operational Taxonomic Unit ◽

The United States ◽

Historical Control ◽

Control Group ◽

Phase 2 ◽

Open Label ◽

Two Phase

Abstract Background Recurrent Clostridium difficile infections (rCDI) are a public health threat with insufficient treatment options at present. Two Phase 2 clinical studies have reported the efficacy of RBX2660, a standardized, stabilized microbiota-based drug, in preventing rCDI. For one of these trials, we report herein the durability of clinical response (lack of CDI recurrence) and microbiome restoration to 12 months after RBX2660 treatment. Methods Data were drawn from an interim analysis of a multicenter, open-label Phase 2 study in which participants with multi-recurrent rCDI received up to 2 doses of RBX2660 delivered via enema 7 days apart; this analysis includes data to 12 months after treatment, with follow-up ongoing. Efficacy was defined as the absence of CDI recurrence to 56 days after the last dose; and durability is defined as a continued lack of reported recurrence. Participant stool samples collected prior to and at 1, 7, 30, 60 days and 6 and 12 months after treatment were sequenced using a shallow shotgun method, with only treatment responders reported herein. Operational taxonomic unit (OTU) data were used to calculate relative abundance at the class level and Microbiome Health Indices. Results This study included 149 RBX2660-treated participants and 110 historical control patients, in the United States and Canada. As previously reported, the efficacy of RBX2660 in preventing rCDI (79.9%; 119/149) was higher than CDI-free rates in the historical control group (51.8%, 57/110; P < 0.001). Of 109 participants who had a 6-month follow-up, 97.2% (106/109) remained CDI-free, and no new CDI recurrences were reported at 12 months. Among treatment responders, the microbiome composition was restored after treatment to predominance by Bacteroidia- and Clostridia-class bacteria, and these compositions remained stable to 12 months after treatment among participants who provided samples. Conclusion RBX2660, a microbiota-based drug, was efficacious for preventing rCDI, with clinical and microbiome restoration durability to at least 12 months after treatment. The follow-up of efficacy, safety, and microbiome restoration are ongoing. Disclosures All authors: No reported disclosures.

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Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): A pooled analysis of two phase II trials with pazopanib and lenvatinib.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4109 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4109-4109

Author(s):

Jorge Hernando-Cubero ◽

Enrique Grande ◽

Daniel E. Castellano ◽

Toni Ibrahim ◽

Nicola Fazio ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Liver Toxicity ◽

Task Force ◽

Pooled Analysis ◽

Phase Ii Trials ◽

Open Label ◽

Two Phase ◽

Phase Ii Studies ◽

Grade 3

4109 Background: Retrospective data in some cancer types suggested a possible different toxicity profile with chemotherapy and targeted therapies according to gender. However, data from prospective studies are still very limited, especially in infrequent tumors such as NETs. Methods: Pts with advanced pancreatic and gastrointestinal NETs treated with pazopanib or lenvatinib in the multicenter open-label phase II studies PAZONET and TALENT respectively, were included in the analysis. Both studies were performed by Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All toxicity grades with an incidence higher than 5% were considered for univariate review. Additionally, all grade 3-4 toxicities were analyzed separately. Results: 155 pts (47.7% female) with 1213 adverse events (AEs) (20% G3-4) divided in 121 categories were included. In female patients, liver toxicity, headache, pyrexia, nausea/vomiting, hair/skin disorders and dizziness were significantly more common (table). The only toxicity with higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p 0.02). There were no gender differences in grade 3-4 toxicities. Conclusions: We observed significant differences in toxicity AEs by gender in two prospective phase II studies with MKIs in NETs patients. Potential different approach to manage toxicity may be adopted based on gender. [Table: see text]

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Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: A prospective, open-label, uncontrolled study

Clinical Therapeutics ◽

10.1016/j.clinthera.2008.01.015 ◽

2008 ◽

Vol 30 (1) ◽

pp. 143-151 ◽

Cited By ~ 127

Author(s):

Nikolaos Markou ◽

Sophia L Markantonis ◽

Efthimios Dimitrakis ◽

Dimitris Panidis ◽

Eleni Boutzouka ◽

...

Keyword(s):

Critically Ill ◽

Intravenous Administration ◽

Critically Ill Patients ◽

Multidrug Resistant ◽

Serum Concentrations ◽

Open Label ◽

Gram Negative ◽

Uncontrolled Study

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Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study

Journal of Neurology ◽

10.1007/s00415-015-7883-4 ◽

2015 ◽

Vol 262 (11) ◽

pp. 2539-2547 ◽

Cited By ~ 9

Author(s):

Mariano Serrao ◽

Alberto Ranavolo ◽

Carmela Conte ◽

Chiara Davassi ◽

Silvia Mari ◽

...

Keyword(s):

Parkinson Disease ◽

De Novo ◽

Open Label ◽

Uncontrolled Study ◽

Rotigotine Treatment

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Prophylactic Treatment of Migraine with Gamma-Linolenic and Alpha-Linolenic Acids

Cephalalgia ◽

10.1046/j.1468-2982.1997.1702127.x ◽

1997 ◽

Vol 17 (2) ◽

pp. 127-130 ◽

Cited By ~ 12

Author(s):

W Wagner ◽

U Nootbaar-Wagner

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Prophylactic Treatment ◽

Nausea And Vomiting ◽

Open Label ◽

Self Medication ◽

Uncontrolled Study

Polyunsaturated fatty acids (PUFA) were administered to 168 patients over a period of 6 months in an open-label uncontrolled study. In 129 patient available for study, 86% experienced reduction in severity, frequency and duration of migraine attacks, 22% became free of migraine and more than 90% had reduced nausea and vomiting. Self-medication changed to simple analgesics in the majority except in 14% of patients without improvement.

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