Pharmacokinetics, safety, and tolerability of four 28-day cycle intramuscular injections for risperidone-ISM 75 mg in patients with schizophrenia: A phase-2 randomized study (PRISMA-2)

2016 ◽  
Vol 33 (S1) ◽  
pp. s240-s241 ◽  
Author(s):  
L. Anta ◽  
J. Llaudó ◽  
I. Ayani ◽  
B. Gorostidi ◽  
M. Monreal ◽  
...  
Keyword(s):  
Injection Site ◽  
Drug Administration ◽  
Randomized Study ◽  
Deltoid Muscle ◽  
Study Medication ◽  
Open Label ◽  
Active Moiety ◽  
Intramuscular Injections ◽  
Competing Interest ◽  
Long Acting

IntroductionRisperidone-ISM is a new long acting intramuscular formulation of risperidone, for monthly administration without oral supplementation.ObjectiveTo characterize the pharmacokinetic of risperidone over multiple intramuscular injections in patients with schizophrenia.MethodA multicenter, open label, two-arm, parallel design clinical trial was performed. Each patient received 4 intramuscular injections of 75 mg of risperidone-ISM in either, gluteal or deltoid muscle at 28-day intervals.ResultsA total of 70 patients were randomized, 67 received at least one dose of study medication. Preliminary data show that mean Cmax of the active moiety was achieved 24-48 hours (Tmax) after each administration and ranged over four consecutive doses from 39.6-53.2 ng/mL and 54.1-61 ng/mL, when given in gluteal or deltoid, respectively. All subjects achieved therapeutic levels (> 7.5 ng/mL for the active moiety) between 2-8 hours after drug administration. The mean concentrations were maintained above therapeutic levels throughout the 4-week dosing period. No significance changes across the study were observed, either on Positive and Negative Syndrome Scale or Extrapyramidal Symptoms Scale. Overall, 63 subjects (94%) experienced at least 1 Treatment Emergent Adverse Event (TEAE) during the study. One serious TEAE (dystonia) was related to study treatment. One death not related to study medication was informed. The most frequently reported TEAEs were hyperprolactinaemia (57.7%) and injection site pain (32.8%).ConclusionsRisperidone-ISM achieved therapeutic levels from the first hours after drug administration and provided a sustained release throughout the 4-weeks dosing period over multiple intramuscular injections independently of the injection site. Risperidone-ISM was found to be safe and well tolerated.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study

PLoS Medicine ◽  
2019 ◽  
Vol 16 (6) ◽  
pp. e1002839 ◽  
Author(s):  
Gary J. Weil ◽  
Joshua Bogus ◽  
Michael Christian ◽  
Christine Dubray ◽  
Yenny Djuardi ◽  
...  
Keyword(s):  
Lymphatic Filariasis ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Randomized Study ◽  
Open Label ◽  
Cluster Randomized

scholarly journals One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study

2020 ◽  
Vol 11 ◽  
pp. 204062072096613
Author(s):  
Hubert Schrezenmeier ◽  
Austin Kulasekararaj ◽  
Lindsay Mitchell ◽  
Flore Sicre de Fontbrune ◽  
Timothy Devos ◽  
...  
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Controlled Trial ◽  
Randomized Study ◽  
Phase Iii ◽  
Complement Inhibitor ◽  
Open Label ◽  
Evaluation Period ◽  
Open Label Extension ◽  
Primary Evaluation ◽  
Long Acting

Background: Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in complement inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results with up to 52 weeks of treatment. Methods: Patients assigned to ravulizumab every 8 weeks (q8w) or eculizumab every 2 weeks during the randomized primary evaluation period received ravulizumab q8w during the 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization, transfusion avoidance, breakthrough hemolysis (BTH), LDH levels, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and stabilized hemoglobin. Serum free C5 levels and safety were assessed. Outcomes as of the data cut-off (4 September 2018) were summarized using descriptive statistics. Results: Overall, 124 patients continued ravulizumab, and 119 switched from eculizumab to ravulizumab. During the extension, 43.5% and 40.3% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved LDH normalization; 76.6% and 67.2% avoided transfusion. BTH decreased in the eculizumab–ravulizumab arm; no events were associated with free C5 ⩾0.5 μg/mL while receiving ravulizumab. Overall, 73.4% and 65.5% of patients in the ravulizumab–ravulizumab and eculizumab–ravulizumab arms, respectively, achieved stabilized hemoglobin. Similar proportions of patients achieved ⩾3-point improvement in FACIT-Fatigue at week 52 (ravulizumab–ravulizumab, 64.5%; eculizumab–ravulizumab, 57.1%). All patients maintained free C5 <0.5 μg/mL during the ravulizumab extension, including those who experienced C5 excursions ⩾0.5 μg/mL while receiving eculizumab during the primary evaluation period. Adverse events were comparable between groups and decreased over time. Conclusion: In adult, complement inhibitor–naïve patients with PNH, ravulizumab q8w for up to 52 weeks demonstrated durable efficacy and was well tolerated, with complete and sustained free C5 inhibition and a decreased incidence of BTH with no events associated with loss of free C5 control. Trial registration: ClinicalTrials.gov identifier, NCT02946463

scholarly journals Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study

2021 ◽  
Author(s):  
John T. Anderson ◽  
Vincent R. Bonagura ◽  
Juthaporn Cowan ◽  
Connie Hsu ◽  
S. Shahzad Mustafa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Injection Site ◽  
Primary Immunodeficiency ◽  
Flow Rate ◽  
Immunoglobulin G ◽  
Randomized Study ◽  
Open Label ◽  
Serum Igg Levels ◽  
Trough Levels ◽  
Infusion Duration

Abstract Purpose To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (> 25 mL and > 25 mL/h per injection site) in patients with primary immunodeficiency. Methods The Hizentra® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25–50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25–100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study. Conclusion Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times. Trial Registration NCT03033745; registered January 27, 2017

A COMPARISON OF PLASMA 17-HYDROXYCORTICOSTEROID LEVELS WITH THE URINARY EXCRETION OF 17-KETOGENIC STEROIDS AND 17-KETOSTEROIDS

1960 ◽  
Vol XXXIV (IV) ◽  
pp. 524-530 ◽  
Author(s):  
Per Lingjoerde ◽  
Knut Kirkeby ◽  
Gunnar Hangård
Keyword(s):  
Urinary Excretion ◽  
Negative Correlation ◽  
Cortical Response ◽  
Intermediate Position ◽  
Urinary Concentration ◽  
Chronic Polyarthritis ◽  
Intramuscular Injections ◽  
Long Acting

ABSTRACT Plasma 17-OHCS and urinary excretion of 17-KGS and 17-KS have been compared in 24 patients with chronic polyarthritis, who had been treated for years with corticosteroids. All medication was discontinued 3 days before this investigation. To test the adrenal cortical response the patients were given intramuscular injections of 40 IU of a long-acting ACTH preparation twice daily on 6 consecutive days. Plasma 17-OHCS were determined at 8 a. m. before the first ACTH injection and 3 hours after the injection on the first and sixth treatment days. The urinary concentration of 17-KGS and 17-KS were measured in 24 hour samples on the control day, and on the first and sixth days of treatment. The results show a greater variation in the 17-KS groups than in the 17-KGS and 17-OHCS groups, the smallest variation being in the 17-OHCS groups. There is a significant increase in all values after the first ACTH injection and a further significant increase after the sixth injection, but the t-values are much larger in the 17-OHCS groups than in the 17-KS groups, while the 17-KGS groups occupy an intermediate position. The plasma 17-OHCS values correlate better with the urinary 17-KGS than with the 17-KS. The correlation between 17-OHCS and 17-KGS is not very good (P > 0.05). There is a negative correlation between 17-OHCS and 17-KS control values, and the correlation after ACTH is very poor. 17-KGS correlate well with 17-KS (P < 0.01).

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