scholarly journals A Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Two Sequential Doses of NV-5138 SPN-820 on Quantitative Electroencephalography in Healthy Adult Males

2021 ◽  
Author(s):  
Leonard J Trejo ◽  
Roman Rosipal ◽  
Adrienne Moore ◽  
Brendan Lujan
Keyword(s):  
Adverse Events ◽  
Healthy Adult ◽  
Spectral Band ◽  
Controlled Study ◽  
Adult Males ◽  
Quantitative Electroencephalography ◽  
Double Blind ◽  
Positive Effects ◽  
Eyes Open ◽  
High Beta

NV-5138 (or SPN-820) is a novel small molecule activator of the mechanistic target of rapamycin complex 1 (mTORC1) currently under development for use in treatment- resistant depression. This phase I study evaluated the safety, tolerability, and pharmacodynamics (as measured by quantitative electroencephalography, qEEG) of two sequential oral doses of NV-5138 in healthy adult males. Twenty-five participants were randomly assigned to double-blind treatment with a single dose of placebo or 2400 mg NV-5138 on Day 1, and a second dose of the same treatment on Day 3. The two doses of NV-5138 were safe and well tolerated, with no deaths, serious adverse events, or discontinuations due to adverse events. Spectral band amplitudes, derived frequency measures, and magnitude squared coherences were computed from qEEG recordings during resting state eyes-open and eyes-closed conditions at multiple timepoints. In the NV-5138 group only, significant changes in qEEG measures occurred at 1 hour post-dose on both days (near NV-5138 T max ), including decreases in low-frequency band amplitudes (theta) and increases in high-frequency EEG band amplitudes (high beta and gamma). These effects were mirrored by a decrease in the theta/beta ratio, a measure negatively associated with arousal and cognitive processing capability. Significantly increased high beta and gamma band coherences were also detected at several specific electrode pairs in both eyes-open and eye-closed conditions. NV-5138 actively modulated functional brain parameters consistent with positive effects on mood, cognition, and arousal. These results indicate that qEEG measures may be useful biomarkers of NV-5138 target engagement and related changes in neural activity.

Bioabsorbable dressing impregnated with betamethasone and ciprofloxacin after endoscopic sinus surgery: A randomized, double-blind, placebo-controlled study

2021 ◽  
pp. 014556132110624
Author(s):  
Małgorzata Wierzchowska ◽  
Paulina Kalińczak-Górna ◽  
Błażej Grześkowiak ◽  
Kamil Radajewski ◽  
Jakub Burduk ◽  
...  
Keyword(s):  
Endoscopic Sinus Surgery ◽  
Healing Process ◽  
Nasal Packing ◽  
Sinus Surgery ◽  
Controlled Study ◽  
Nasal Surgery ◽  
Double Blind ◽  
Nasal Blockage ◽  
Positive Effects ◽  
Mucosal Edema

Background In addition to its hemostatic and stabilization role, biodegradable nasal packing can be used as a carrier for drugs after functional endoscopic sinus surgery (FESS). The aim of this study was to compare the influence of biodegradable synthetic polyurethane foam (NasoPore) soaked with ciprofloxacin, or betamethasone, or both to the same foam soaked with saline after FESS. Methods 120 adults with chronic rhinosinusitis, with and without polyps, directed for bilateral full-house FESS were enrolled for the study. The patients were randomized and blinded into 3 groups, depending on the type of postoperative procedure applied. Thus, NasoPore soaked with antibiotic was provided to the first group; in the second group, the steroid was used; and the combination of both, in the third group. In each case, the aforementioned procedure was administered on one side of the nose, while NasoPore was soaked in saline on the other, at the end of the surgery, respectively. The patients were requested to complete a questionnaire during their postoperative visits at 2, 10, 30, 90, and 180 days, scoring the level of complaints on the VAS scale, separately for each side. The evaluation of the healing process was performed at each visit using rigid endoscopy and subsequently rated on numerical scales. Results Decreased mucosal edema and secretion; reduced Lund-Kennedy score; and favorable influences on facial pressure, nasal blockage, and smell were most evidently seen in the group receiving the antibioticsteroid combination. Conclusions The application of biodegradable nasal packing with betamethasone and ciprofloxacin in sino-nasal surgery has positive effects not only on the healing process but also impacts patient’s comfort. To optimize it, however, further research is needed.

Analysis of acute naproxen administration on memory in young adults: A randomized, double-blind, placebo-controlled study

2017 ◽  
Vol 31 (10) ◽  
pp. 1374-1376
Author(s):  
Jack H Wilson ◽  
Amy H Criss ◽  
Sean A Spangler ◽  
Katherine Walukevich ◽  
Sandra Hewett
Keyword(s):  
Young Adults ◽  
Healthy Adult ◽  
Adult Population ◽  
Critical Role ◽  
Random Order ◽  
Controlled Study ◽  
High Dose ◽  
Short Term ◽  
Double Blind ◽  
Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs work by non-selectively inhibiting cyclooxygenase enzymes. Evidence indicates that metabolites of the cyclooxygenase pathway play a critical role in the process of learning and memory. We evaluated whether acute naproxen treatment impairs short-term working memory, episodic memory, or semantic memory in a young, healthy adult population. Participants received a single dose of placebo or naproxen (750 mg) in random order separated by 7–10 days. Two hours following administration, participants completed five memory tasks. The administration of acute high-dose naproxen had no effect on memory in healthy young adults.

scholarly journals A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 296
Author(s):  
Irina Kiseleva ◽  
Irina Isakova-Sivak ◽  
Marina Stukova ◽  
Marianna Erofeeva ◽  
Svetlana Donina ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Phase 1 ◽  
Healthy Adults ◽  
Controlled Study ◽  
Temperature Sensitive ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Human Influenza Virus ◽  
Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

scholarly journals Rice Bran Supplement Containing A Functional Substance, the Novel Peptide Leu-Arg-Ala, has Anti-Hypertensive Effects: A Double-Blind, Randomized, Placebo-Controlled Study

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 726
Author(s):  
Ogawa ◽  
Shobako ◽  
Fukuhara ◽  
Satoh ◽  
Kobayashi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Placebo Group ◽  
Adverse Events ◽  
Rice Bran ◽  
Test Group ◽  
Normal Blood ◽  
Controlled Study ◽  
The Novel ◽  
Normal Blood Pressure ◽  
Double Blind

The anti-hypertensive effect of processed rice bran (PRB) was recently reported, for which the novel peptide Leu-Arg-Ala (LRA) was identified as the functional substance. The purpose of this study was to assess the anti-hypertensive effects of a rice bran supplement containing PRB in individuals with high-normal blood pressure (systolic blood pressure (SBP): 130–139 mmHg and/or diastolic blood pressure (DBP): 85–89 mmHg) or grade 1 hypertension (SBP: 140–159 mmHg and/or DBP: 90–99 mmHg). One hundred individuals with high-normal blood pressure or grade 1 hypertension were recruited to participate in this double-blind, randomized, placebo-controlled study. Participants were randomly allocated to the placebo group (n = 50) or the test group (n = 50). Each group took four test tablets (43 μg LRA/day) or four placebo tablets daily. The decrease in blood pressure in the test group compared with the placebo group was the primary outcome. Adverse events were recorded and hematological/urinary parameters measured to determine the safety of the supplement, which was the secondary outcome. In total, 87 participants completed the study. The SBP of the test group at 12 weeks was significantly lower than that of the placebo group (p = 0.0497). No serious adverse events were observed. Daily consumption of a rice bran supplement containing PRB can safely improve mildly elevated blood pressure.

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 Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

2016 ◽  
Vol 76 (5) ◽  
pp. 811-820 ◽  
Author(s):  
Thomas Bardin ◽  
Robert T Keenan ◽  
Puja P Khanna ◽  
Jeff Kopicko ◽  
Maple Fung ◽  
...  
Keyword(s):  
Adverse Events ◽  
Laboratory Data ◽  
Standard Of Care ◽  
Phase Iii ◽  
Controlled Study ◽  
Inadequate Response ◽  
Double Blind ◽  
Significant Treatment ◽  
End Points ◽  
Registration Number

ObjectivesDetermine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.MethodsPatients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.ResultsPatients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.ConclusionLesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.Trial registration numberNCT01493531.

scholarly journals 167 Randomized, Double-Blind, Active-Controlled Study of Starting Aripiprazole Lauroxil with 1-Day Initiation in Acutely Ill Patients with Schizophrenia

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 306-307
Author(s):  
Peter J. Weiden ◽  
Amy Claxton ◽  
Yangchun Du ◽  
Sergey Yagoda ◽  
David Walling ◽  
...  
Keyword(s):  
Adverse Events ◽  
Outpatient Setting ◽  
Controlled Study ◽  
Injection Site Pain ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Secondary Analyses ◽  
Site Pain ◽  
Over Time ◽  
Funding Acknowledgements

Abstract:Objective:Evaluate efficacy and safety of a 2-month dose of aripiprazole lauroxil (AL) with a 1-day initiation regimen during hospitalization for an acute exacerbation of schizophrenia.Methods:In the phase 3b double-blind ALPINE study, adults with schizophrenia were randomized to AL (AL NanoCrystal® Dispersion + oral aripiprazole 30 mg day 1; AL 1064 mg day 8 and every 8 weeks) or paliperidone palmitate (PP 234 mg day 1; PP 156 mg day 8 and every 4 weeks). Patients were discharged after 2 weeks of hospitalization and followed through week 25. Primary endpoint was within-group changes in PANSS total score from baseline to week 4 (observed cases). Secondary analyses included within-group changes at weeks 9 and 25 (observed) and between-group comparisons at weeks 4, 9, and 25 (MMRM). Adverse events (AEs) were monitored throughout the study.Results:200 patients were randomized (AL, n=99; PP, n=101); 56.6% and 42.6%, respectively, completed the study. Within-group changes from baseline in PANSS were −17.4 for AL and −20.1 for PP at week 4 (both groups, P<0.001) and continued to decline at weeks 9 (AL, −19.8; PP, −22.5) and 25 (AL, −23.3; PP, −21.7). The change in PANSS over time was similar between groups. AEs occurring in ≥10% of patients in either group were injection site pain (AL, 17.2%; PP, 24.8%), akathisia (AL, 9.1%; PP, 10.9%), and weight increased (AL, 9.1%; PP, 16.8%).Conclusions:AL and PP were effective and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing in the outpatient setting.Funding Acknowledgements:This study was funded by Alkermes, Inc.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal Of Rivaroxaban-Induced Anticoagulation In Healthy Subjects By Andexanet Alfa (PRT064445), An Antidote For Fxa Inhibitors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3636-3636 ◽  
Author(s):  
Crowther Mark ◽  
Mathur Vandana ◽  
Kitt Michael ◽  
Lu Genmin ◽  
Pamela B. Conley ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Subjects ◽  
Controlled Study ◽  
Pharmacokinetic Data ◽  
Phase 2 ◽  
Employment Equity ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Equity Ownership ◽  
Andexanet Alfa

Abstract Background Direct factor Xa inhibitors have demonstrated compelling anticoagulant efficacy and/or safety profiles across multiple diverse patient populations. A specific antidote to reverse anticoagulation during episodes of serious uncontrolled bleeding or before urgent/emergent surgery is lacking. Andexanet alfa (proposed INN)(AnXa, PRT064445) is a modified, recombinant human fXa molecule that is catalytically inactive but retains high-affinity binding to direct fXa inhibitors. It thus acts as a decoy to reverse fXa inhibitor-mediated anticoagulation in preclinical and early clinical studies. Methods This ongoing Phase 2, double-blind, placebo-controlled study is examining the reversal by AnXa of the anticoagulant activity of rivaroxaban (riva), as well as the pharmacokinetics and safety in healthy subjects. Reversal of riva anticoagulation will be studied with up to 6 different dose cohorts/ regimens of AnXa or placebo in a 6:3 ratio (i.e., 9 subjects per cohort). Riva is administered at an oral dose of 20 mg qd for 6 days and AnXa administered intravenously on Day 6, 3 hours after the last riva dose – the approximate time of maximum riva concentration (mean ± SD: 0.64 ± 0.22 mM, n=18). Pharmacodynamic and safety data are collected through Day 48 with pharmacokinetic data through Day 10. Results We report here available data from the first 2 AnXa dose cohorts (210 mg and 420 mg, n =18). Immediately after completion of the 210 mg and 420 mg doses, anti-fXa activity decreased dose-dependently by 20% and 53%, respectively, from the pre-AnXa level and returned to placebo levels by approximately 2 hours after treatment (Figure). In parallel, the plasma concentrations of unbound riva were decreased by 32% and 51%, respectively, relative to pre-AnXa values. In addition, riva-induced inhibition of thrombin generation and prolongation of both prothrombin time and activated clotting time were also rapidly partially reversed by AnXa in a dose-dependent manner. At 2 minutes after AnXa administration, the molar ratio of AnXa to total plasma riva was 0.8 for the 210 mg dose (1.2 µM/1.6 µM, respectively) and 1.2 for the 420 mg dose (2.6 µM/2.1 µM, respectively). AnXa infusion was not associated with increases in prothrombin fragments F1+2, thrombin-antithrombin, or D-dimer (all values were within normal ranges). As expected, tissue factor pathway inhibitor activity decreased due to its binding to AnXa. AnXa was well tolerated and there were no thrombotic events, serious, or severe adverse events. Adverse events occurring in 1 or more AnXa or placebo recipients included infusion-related reactions (n = 3, all mild in severity) and post-procedural hematoma, headache, or postural dizziness (n = 2 each). Summary/Conclusions Results from this ongoing clinical trial demonstrate that AnXa is able to dose-dependently partially reverse the anticoagulant effects of rivaroxaban, as assessed by pharmacodynamic markers, in healthy subjects. These data are consistent with previously reported results with apixaban in that AnXa sequesters rivaroxaban and apixaban in a similar stoichiometric manner. Additional data with higher doses of AnXa will also be presented. AnXa is well-tolerated and a potentially promising, universal antidote for fXa inhibitors. Disclosures: Mark: Portola Pharmaceuticals: Consultancy. Off Label Use: The use of PRT064445 as an antidote for reversal of anticoagulation from direct and indirect fXa inhibitors is investigational. Vandana:Portola Pharmaceuticals: Consultancy. Michael:Portola Pharmaceuticals: Employment, Equity Ownership. Genmin:Portola Pharmaceuticals: Employment, Equity Ownership. Conley:Portola Pharmaceuticals: Employment, Equity Ownership. Stanley:Portola Pharmaceuticals: Employment, Equity Ownership. Castillo:Portola Pharmaceuticals: Employment, Equity Ownership. Hutchaleelaha:Portola Pharmaceuticals: Consultancy. Karbarz:Portola Pharmaceuticals: Employment. Lin:Portola Pharmaceuticals: Employment. Barron:Portola Pharmaceuticals: Employment. Russell:Portola Pharmaceuticals: Employment. Levy:Portola Pharmaceuticals: Employment. Connolly:Portola Pharmaceuticals: Consultancy. Curnutte:Portola Pharmaceuticals: Employment, Equity Ownership.

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