scholarly journals First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study

2019 ◽  
Vol 6 (1) ◽  
pp. e000354 ◽  
Author(s):  
Viktoria Hermann ◽  
Anastas Batalov ◽  
Svetlana Smakotina ◽  
Pierre-Eric Juif ◽  
Peter Cornelisse
Keyword(s):  
Lymphocyte Count ◽  
Activity Index ◽  
Plasma Concentrations ◽  
Total Lymphocyte Count ◽  
Controlled Study ◽  
Double Blind ◽  
Once Daily ◽  
Receptor Modulator ◽  
Total Lymphocyte ◽  
Dsdna Antibodies

ObjectiveTo investigate the pharmacodynamics, pharmacokinetics and safety of cenerimod—a potent, oral, selective sphingosine 1-phosphate 1 receptor modulator—in patients with SLE.MethodsThis multicentre, double-blind, placebo-controlled study was conducted in two parts. In part A, patients with SLE were randomised 1:1:1:1 to receive oral cenerimod 0.5, 1 or 2 mg, or placebo once daily for 12 weeks. Following an interim safety review of part A, additional patients were randomised 3:1 for part B and received cenerimod 4 mg or placebo once daily for 12 weeks. Endpoints included changes in total lymphocyte count, SLE Disease Activity Index-2000 (SLEDAI-2K) score (modified (mSLEDAI-2K) to exclude leucopenia), biomarker anti-double-stranded DNA (anti-dsDNA) antibodies, pharmacokinetic assessments and treatment-emergent adverse events (TEAEs).ResultsPart A included 49 patients (1:1:1:1 receiving cenerimod 0.5, 1 or 2 mg, or placebo) and part B included 18 patients (13 cenerimod; 5 placebo). Cenerimod caused a statistically significant dose-dependent reduction in total lymphocyte count from baseline to end of treatment (EOT). Compared with placebo at EOT, cenerimod 4 mg had an estimated treatment effect on change from baseline in mSLEDAI-2K score of −2.420 (p=0.0306), and on anti-dsDNA antibodies of −64.55 U/mL (p=0.0082), suggesting clinical and biological improvement in these exploratory efficacy analyses. Trough plasma concentrations were dose proportional and reached steady-state conditions after 4 weeks of once daily dosing. All groups reported similar, non-dose-related frequencies of TEAEs (cenerimod 0.5 mg: 41.7%; 1 mg: 41.7%; 2 mg: 46.2%; 4 mg: 38.5% and placebo: 58.8%). A small, dose-related, non-clinically relevant decrease in heart rate was only observed in the first 6 hours after initiation.ConclusionsWith an acceptable safety profile, the efficacy findings suggest that cenerimod has the potential to treat patients with SLE. Further investigation in larger patient populations with longer treatment duration is warranted.

scholarly journals 179 Dasotraline in Children With Attention Deficit Hyperactivity Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Study

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 102-103
Author(s):  
Robert Goldman ◽  
Lenard Adler ◽  
Thomas Spencer ◽  
Robert Findling ◽  
Seth C. Hopkins ◽  
...  
Keyword(s):  
Weight Loss ◽  
Repeated Measures ◽  
Mixed Model ◽  
Rating Scale ◽  
Plasma Concentrations ◽  
Fixed Dose ◽  
Controlled Study ◽  
Double Blind ◽  
Once Daily ◽  
Stable Plasma

AbstractObjectivesOnce-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated dasotraline in children aged 6–12 years (NCT02428088).MethodsPatients were randomized 1:1:1 to 6 weeks of once-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo. The primary efficacy endpoint was change from baseline (CFB) at Week 6 in ADHD Rating Scale Version IV – Home Version (ADHD RS-IV HV) total score, using a mixed model for repeated measures (MMRM) in the intent-to-treat (ITT) population. Secondary endpoints included Clinical Global Impression-Severity (CGI-S) score and safety endpoints.ResultsThe mean age of 342 randomized patients was 9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% of patients completed the study. In the ITT population (N=336), ADHD RS-IV HV total score improved significantly with dasotraline 4 mg/day vs placebo(least squares [LS] mean [SE] CFB at Week 6: –17.53 [±1.31] vs –11.36 [±1.29], respectively, p<0.001; effect size [ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/day vs placebo at Week 6 (p=0.001, p=0.003, respectively). Improvement in CGI-S score was statistically significant with dasotraline 4 mg/day vs placebo(LS mean [SE] CFB at Week 6: –1.39 [±0.12] vs –1.04 [±0.12], respectively, p=0.040; ES: 0.29). No significant improvement was observed on the ADHD RS-IV HV total score and the CGI-S score for dasotraline 2 mg/day vs placebo. The most frequent treatment-emergent AEs (≥5% and higher than placebo) were (2 mg/day; 4 mg/day; placebo): insomnia (15.3%; 21.7%; 4.3%, all terms combined), decreased appetite (12.6%; 21.7%; 5.2%), weight loss (5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%), nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%; 5.2%; 2.6%).ConclusionsCompared with placebo, dasotraline 4 mg/day significantly improved ADHD symptoms in children, as assessed by ADHD RS-IV HV total score and inattentiveness and hyperactivity/impulsivity subscale scores. Dasotraline was generally well tolerated; most common AEs were insomnia, decreased appetite, weight loss and irritability.Funding AcknowledgementsStudy sponsored by Sunovion Pharmaceuticals Inc.

scholarly journals Effect of N-Acetylcysteine on IL-10 and Total Lymphocyte Count in HIV Infected Patients Undergoing Antiretroviral Treatment

2021 ◽  
Vol 22 (2) ◽  
pp. 114-118
Author(s):  
Filia Yuniza ◽  
Eddy Mart Salim ◽  
Zen Hafy ◽  
Nova Kurniati ◽  
Harun Hudari ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Antiretroviral Therapy ◽  
Lymphocyte Count ◽  
Antiretroviral Treatment ◽  
Total Lymphocyte Count ◽  
Aids Patients ◽  
Double Blind ◽  
Total Lymphocyte ◽  
Hiv Aids

Objective: To determine NAC oral administration’s effect on changes in IL-10 levels and total lymphocyte count (TLC) in patients with HIV/AIDS in Dr Mohammad Hoesin Hospital, Palembang. Material and Methods: This study was a double-blind, randomized clinical trial. A total of 32 HIV/AIDS patients undergoing ARV treatment were randomly divided into two groups: the placebo and NAC groups. In the placebo group, patients were given capsules containing lactose at a dose of 3x1 capsules/ day, while the NAC group, were given NAC at a dose of 3x200 mg/day. Each group was treated for 12 weeks. Results: NAC administration significantly reduced IL-10 levels P= 0.038 but could not significantly increase TLC after treatment P= 0.376. However, TLC on the NAC group remained higher when compared with TLC on the placebo group. Conclusion: NAC administration significantly reduced levels of IL-10 and increased TLC; therefore, NAC has potential effects of increasing the effectiveness of antiretroviral therapy in HIV/AIDS patients, although it still needs to be studied further. J MEDICINE 2021; 22: 114-118

Correlation between total and CD4 lymphocyte counts in HIV infection: not making the good an enemy of the not so perfect

1996 ◽  
Vol 7 (6) ◽  
pp. 422-428 ◽  
Author(s):  
E J Beck ◽  
E J Kupek ◽  
M M Gompels ◽  
A J Pinching
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Lymphocyte Count ◽  
Cell Subset ◽  
Total Lymphocyte Count ◽  
Aids Patients ◽  
T Cell Subset ◽  
Total Lymphocyte ◽  
Asymptomatic Patients ◽  
Cd4 Lymphocyte

The aim of this study was to assess the correlation and average cost of total lymphocyte count compared with CD4 count as a broad estimate of immunosuppression in HIV-1 infected individuals. Spearman's partial rank correlation were calculated between total lymphocyte count, absolute CD4 count and CD4 per cent stratified by stage of HIV-1 infection for routinely collected samples. Data were collected prospectively from a T cell-subset register combined with clinical data obtained retrospectively from case notes of HIV-infected patients managed at St Mary's Hospital, London 1982-1991. Costing data were obtained through a survey of the departments of haematology and immunology 1989 90 prices . The correlation between 1534 paired absolute lymphocyte count and CD4 lymphocyte count was found to be high R 0.76 . When analysed by stage of HIV infection, the correlation increased from R 0.64 for asymptomatic patients, to R 0.72 for patients with symptomatic non-AIDS HIV infection and R 0.73 for AIDS patients. Correlations between absolute lymphocyte count and CD4 per cent were considerably weaker: R 0.41 all paired counts; R 0.32 for asymptomatic patients; R 0.25 for symptomatic non-AIDS patients; R 0.32 for AIDS patients. Average cost was 8 per full blood count compared with 38 per T-cell subset analysis. The high correlation between total and CD4 lymphocyte counts, especially for patients with symptomatic HIV disease, demonstrates the suitability of the use of total lymphocyte count in the absence of CD4 counts. Given the considerably lower prices of total lymphocyte counts compared with T-cell subset analysis, this is particularly relevant for developing countries.

Serum albumin and total lymphocyte count as predictors of outcome in hip fractures

2010 ◽  
Vol 29 (1) ◽  
pp. 89-93 ◽  
Author(s):  
Brendan J. O'Daly ◽  
James C. Walsh ◽  
John F. Quinlan ◽  
Gavin A. Falk ◽  
Robert Stapleton ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Hip Fractures ◽  
Lymphocyte Count ◽  
Total Lymphocyte Count ◽  
Predictors Of Outcome ◽  
Total Lymphocyte

scholarly journals Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study

2009 ◽  
Vol 161 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Gudmundur Johannsson ◽  
Ragnhildur Bergthorsdottir ◽  
Anna G Nilsson ◽  
Hans Lennernas ◽  
Thomas Hedner ◽  
...  
Keyword(s):  
Single Dose ◽  
Replacement Therapy ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Double Blind ◽  
Once Daily ◽  
Physiological Serum ◽  
Cortisol Levels ◽  
Dual Release

BackgroundEndogenous plasma cortisol levels have a well-defined circadian rhythm. The aim of this project is to develop a once daily oral dual-release formulation for cortisol replacement therapy that mimics the diurnal variation in the plasma cortisol profile.ObjectiveTo determine single-dose plasma pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release hydrocortisone tablets in healthy volunteers. In addition, the effect of food intake was investigated for the 20 mg dose.DesignA randomised, controlled, two-way cross-over, double-blind, phase I study of oral hydrocortisone (modified (dual) release; 5 and 20 mg) with an open food-interaction arm.MethodsThe single dose pharmacokinetic studies were performed with betamethasone suppression. The two first study days were blinded and randomised between morning administration of 5 and 20 mg tablet in a fasting state. The third day was open with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma samples were assayed using both a validated LC–MS/MS and an immunoassay. The plasma pharmacokinetic variables were calculated using non-compartmental data analysis.ResultsThe time to reach a clinically significant plasma concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431 (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h thereafter and all plasma concentrations 18–24 h after intake were below 50 nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min based on LC–MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced an increase in plasma exposure of cortisol that was not fully dose proportional.ConclusionThe dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.

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