scholarly journals SAFETY OF AMISELIMOD IN HEALTHY SUBJECTS: RESULTS FROM A PHASE 1 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
Stephen Hanauer ◽  
Terry O’Reilly ◽  
Robert Lester ◽  
Neal Slatkin ◽  
Jimin Lee ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Vital Signs ◽  
Controlled Study ◽  
Tolerability Profile ◽  
Double Blind ◽  
Study Drug Administration ◽  
Safety Population ◽  
Physical Examinations ◽  
The Mean

Abstract Objective To evaluate the safety profile of amiselimod, a selective sphingosine 1-phosphate receptor modulator which has been shown to regulate lymphocyte trafficking and is in development for the treatment of inflammatory bowel disease. Methods A randomized, double-blind, multiple-dose, placebo-controlled, parallel study with a nested crossover design evaluated the safety and tolerability profile of amiselimod. Healthy adults were randomized in a 2:1:1 ratio during a 28-day treatment period accordingly: a single dose of placebo followed by oral amiselimod (upwardly titrated in doses ranging from 0.4 to 1.6 mg to achieve 0.4 mg and 0.8 mg steady-state exposure; a single dose of oral moxifloxacin 400 mg followed by placebo; or placebo followed by a single dose of moxifloxacin 400 mg. The safety population included all subjects who received at least one dose of treatment. Adverse events (AE) and serious AEs were collected. Treatment-emergent AEs were defined as an AE that was starting or worsening at the time of or after study drug administration. Changes in clinical laboratory parameters (including lymphocyte counts), physical examinations, vital signs, and electrocardiogram parameters (including heart rate, PR, QRS, and QT intervals) were recorded. Subjects were permitted to withdraw if lymphocyte counts were ≤ 0.2 x 109/L. Results The safety population included 190 subjects of which 95 received amiselimod and 95 were in the combined moxifloxacin group. Subjects were 40% female, 83% white, and the mean (standard deviation) age was 39.0 (8.8) years. The discontinuation rate was 8% (n=8) in the amiselimod group and 4% (n=4) in the moxifloxacin group. Three subjects who received amiselimod discontinued because they met the stopping criteria for low lymphocyte counts. One subject experienced an amiselimod-related serious AE of atrial fibrillation on day 26 (after receiving amiselimod 1.6 mg for 3 of the preceding 4 days) that required hospitalization, cardioversion, and led to discontinuation. No deaths were reported. All other AEs were mild to moderate in severity. Decreased white blood counts were the most commonly reported TEAE, followed by headache and constipation (Table). Reductions in white blood counts returned to normal range after study discontinuation without sequelae. Decreased neutrophils, lymphocytes and hemoglobin, and increased creatine kinase, alanine aminotransferase, and aspartate aminotransferase were reported, all of which resolved without sequelae. The mean absolute lymphocyte count for amiselimod exhibited a gradual decrease from predose (1.681 thou/uL) to a nadir of 0.424 thou/uL on day 27 (Figure). Changes to vital signs, physical examinations, and ECG parameters were within normal limits. Conclusions Upwardly titrated doses of amiselimod ranging from 0.4 to 1.6 mg were generally well tolerated in healthy subjects.

scholarly journals Pharmacokinetics of a Once-Daily Oral Dose of Moxifloxacin (Bay 12-8039), a New Enantiomerically Pure 8-Methoxy Quinolone

1999 ◽  
Vol 43 (11) ◽  
pp. 2793-2797 ◽  
Author(s):  
John T. Sullivan ◽  
Marilyn Woodruff ◽  
John Lettieri ◽  
Vipin Agarwal ◽  
George J. Krol ◽  
...  
Keyword(s):  
High Performance ◽  
Vital Signs ◽  
Blood Chemistry ◽  
Controlled Study ◽  
Pharmacokinetic Parameters ◽  
Fluorometric Detection ◽  
Double Blind ◽  
Time Curve ◽  
Once Daily ◽  
The Mean

ABSTRACT The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C max) and the area under the concentration-time curve from 0 to 24 h (AUC0–24) were 3.4 mg/liter and 30.2 mg · h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg · h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the meanC max/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC andC max/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.

scholarly journals Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary ExtractSceletium tortuosum(Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Simon Chiu ◽  
Nigel Gericke ◽  
Michel Farina-Woodbury ◽  
Vladimir Badmaev ◽  
Hana Raheb ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Rating Scale ◽  
Vital Signs ◽  
Camp Response Element Binding ◽  
Alzheimer’S Dementia ◽  
Controlled Study ◽  
Double Blind ◽  
Alzheimer's Dementia ◽  
Female Ratio ◽  
Element Binding Protein

Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB).Objective. The primary endpoint was to examine the neurocognitive effects of extractSceletium tortuosum(Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects.Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (totaln=21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale.Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P<0.032) and executive function (P<0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated.Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer’s dementia. This trial is registered with ClinicalTrials.govNCT01805518.

TOP-PRO study: A randomized double-blind controlled trial of topiramate versus propranolol for prevention of chronic migraine

Cephalalgia ◽  
2021 ◽  
pp. 033310242110474
Author(s):  
Debashish Chowdhury ◽  
Luv Bansal ◽  
Ashish Duggal ◽  
Debabrata Datta ◽  
Ankit Mundra ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Virus Disease ◽  
Controlled Trial ◽  
Preventive Treatment ◽  
Point Estimate ◽  
Tolerability Profile ◽  
Double Blind ◽  
Significant Difference ◽  
The Mean

Objective The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. Background Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. Methods Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. Results As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was −5.3 ± 1.2 vs −7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of −1.99 with a 95% confidence interval of −5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. Conclusion Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile. Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997)

scholarly journals Percutaneous Mastoid Electrical Stimulator Improves Poststroke Depression and Cognitive F unction in Patients with Ischaemic Stroke: A Prospective, Randomized, Double-blind, and Sham-controlled Study

2020 ◽  
Author(s):  
Taoli Lu ◽  
Lanying He ◽  
Bei Zhang ◽  
Jian Wang ◽  
Lili Zhang ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Sham Group ◽  
Mean Value ◽  
Controlled Study ◽  
Poststroke Depression ◽  
Score Change ◽  
Double Blind ◽  
The Mean ◽  
Electrical Stimulator ◽  
Moca Score

Abstract Background : Poststroke depression can lead to functional dependence, cognitive impairment and reduced quality of life. The aim of this study was to evaluate the effects of a percutaneous mastoid electrical stimulator (PMES) plus antidepressants on poststroke depression and cognitive function. Methods: This study was a prospective, randomized, double-blind, and sham-controlled study . A total of 258 clinically depressed ischaemic stroke patients within 14 days of index stroke were randomly assigned to the PMES plus antidepressant (PMES group, N=125) and sham plus antidepressant (sham group, N=133) groups. All patients underwent the Montreal Cognitive Assessment (MoCA) and Hamilton Rating Scale for Depression (HRSD) test at 2 weeks (baseline), and 6 months(M6) after ischaemic stroke. Primary outcomes were the percentage of patients showing a treatment response (≥50% reduction in HRSD score) and depression remission (HRSD score≤9) at 6 months. The secondary outcome was the percentage of patients with a MoCA score <26 . Results: The percentages of patients showing a treatment response and depression remission were significantly higher in the PMES group than in the sham group (57.60% vs 41.35%, P=0.009; 44.00% vs 29.32%, P=0.014 respectively). The mean value of the HRSD score change [M(month)6-baseline] was significantly higher in the PMES group than in the sham group at 6 months (-11.93 ±5.32 vs -10.48 ± 6.10, P = 0.036, respectively). The percentage of patients with MoCA scores <26 was lower in the PEMS group than in the sham group(12.0% vs 24.06%, P=0.012,respectively), and the mean value of the MoCA score change (M6-baseline) was higher in the PMES group than in the sham group (3.50±2.55 vs 2.72±2.52, P=0.005,respectively). Conclusion: These findings demonstrate that PMES adjunctive to antidepressant therapy is effective in reducing depression, achieving remission in the short term, and improving cognition. Trial registration: This trial was retrospectively registered (registration number: ChiCTR1800016463) on 03 June 2018

scholarly journals A Randomised Controlled Trial on the Efficacy and Safety of Oral Ketamine in Neonatal Circumcision

2021 ◽  
Author(s):  
Victor Ifeanyichukwu Modekwe ◽  
Jideofor Okechukwu Ugwu ◽  
Okechukwu Hyginus Ekwunife ◽  
Andrew Nwankwo Osuigwe ◽  
Jideofor Chukwuma Orakwe ◽  
...  
Keyword(s):  
Placebo Group ◽  
Controlled Trial ◽  
Controlled Study ◽  
Categorical Variables ◽  
Paediatric Surgery ◽  
Peripheral Oxygen Saturation ◽  
Double Blind ◽  
Oral Ketamine ◽  
The Mean ◽  
Neonatal Circumcision

Introduction: Procedural analgesia use in neonatal circumcision is not widespread in the developing world. An easy-to-administer, adequate and safe analgesia will encourage usage in neonatal circumcision. Orally administered ketamine may prove effective and safe, and may encourage procedural analgesia use in neonatal circumcision. Aim: To determine the analgesic efficacy of oral ketamine in Plastibell® neonatal circumcision. Materials and Methods: A hospital based randomised double blind controlled study was conducted at the paediatric surgery unit of the hospital, from March 2015 to December 2015. Total 121 neonates were sequentially recruited, and randomised into two groups. Group A received oral ketamine, and Group B received plain syrup (placebo) as procedural analgesia. Continuous pulse oximeter monitoring was done before, during and immediately after the procedure. The pre-procedural and intra-procedural peripheral oxygen saturation (SpO2) and Pulse Rate (PR) were determined at the various stages. Also, the Neonatal Infant Pain Scale (NIPS) scores were assessed during the stages of the procedure. Differences in mean scores were analysed. Mann-Whitney U test and Independent t-test were used to compare means of continuous variable, while Fisher’s exact test was used to compare categorical variables. Significance was set at p<0.05. Results: Sixty-one neonates received oral ketamine, while 60 received placebo. The intraoperative mean SpO2 were lower in the placebo group and significant at the tying stage with p=0.022. The mean intraoperative PR was higher in the placebo group and significant at dorsal-slit, tying and excision stages (p<0.05). The mean intraoperative NIPS scores were significantly higher in the placebo group. Conclusion: Oral ketamine provides effective and safe analgesia for neonatal Plastibell® circumcision in comparison to placebo.

Effect of Chlorophyllin on Urinary Odor in Incontinent Geriatric Patients

1983 ◽  
Vol 17 (10) ◽  
pp. 732-734 ◽  
Author(s):  
Milap C. Nahata ◽  
Carole A. Slencsak ◽  
Judith Kamp
Keyword(s):  
Visual Analog Scale ◽  
Washout Period ◽  
Geriatric Patients ◽  
Odor Intensity ◽  
Controlled Study ◽  
Analog Scale ◽  
Double Blind ◽  
Mean Intensity ◽  
The Mean ◽  
Percent Decrease

This randomized, double-blind, crossover, placebo-controlled study involved 20 incontinent geriatric patients; all had indwelling Foley catheters. Each patient received chlorophyllin 100 mg/d for two weeks and placebo daily for two weeks, separated by a washout period of one week. For each subject, the intensity of urinary odor was measured ten times during both the treatment and placebo regimen and three times during the washout period, using a visual analog scale. A decrease in urinary odor was associated with chlorophyllin in 12 patients and with placebo in 6 patients at the end of two weeks on each regimen. Chlorophyllin treatment was associated with about a 21-percent decrease in mean urinary odor intensity, whereas placebo increased the odor by about 9 percent. The mean intensity of urinary odor was lowest during the second week of chlorophyllin treatment. Despite the decrease in urinary odor in many patients receiving chlorophyllin, its effect was not significantly greater than that of placebo. Our data suggest that chlorophyllin 100 mg/d for two weeks may not be effective in incontinent geriatric patients with mild to moderate urinary odor.

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