Autoinjector Research Articles

Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results

Objective We compared the pharmacokinetic exposure following a single subcutaneous dose of benralizumab 30 mg using either autoinjectors (AI) or accessorized prefilled syringes (APFS). APFS and AI functionality and reliability for at-home benralizumab delivery have been demonstrated in the GREGALE and GRECO studies, respectively. Methods In the open-label AMES study (NCT02968914), 180 healthy adult men and women were randomized to one of two device (AI or APFS) and three injection site (upper arm, abdomen, or thigh) combinations. Randomization was stratified by weight (<70 kg, 70–84.9 kg, and ≥85 kg). Blood eosinophil counts were measured on Days 1, 8, 29, and 57. Results Benralizumab pharmacokinetic exposure was similar between AI and APFS. Geometric mean ratios (AI/APFS) (90% CI) were 92.8% (87.4–98.6) and 94.5% (88.2–101.2) for two area under the concentration‒time curve measurements (AUClast and AUCinf). Benralizumab exposure was approximately 15–30% greater for thigh vs. abdomen or upper arm administration. Exposure was slightly greater for APFS vs. AI regardless of injection site or weight class. These differences were unlikely to be clinically relevant, as eosinophil depletion was achieved consistently with both devices at all injection sites. No device malfunctions were reported. No new or unexpected safety findings were observed. Conclusion Benralizumab pharmacokinetic exposure was similar between AI and APFS, with consistent blood eosinophil count depletion observed with both devices. These results support benralizumab administration with either AI or APFS, providing patients and physicians increased choice, flexibility, and convenience for potential at-home delivery.

Proximity-Based Emergency Response Communities for Patients With Allergies Who Are at Risk of Anaphylaxis: Clustering Analysis and Scenario-Based Survey Study.

BackgroundAnaphylaxis is a potentially fatal allergic reaction. However, many patients at risk of anaphylaxis who should permanently carry a life-saving epinephrine auto injector (EAI) do not carry one at the moment of allergen exposure. The proximity-based emergency response communities (ERC) strategy suggests speeding EAI delivery by alerting patient-peers carrying EAI to respond and give their EAI to a nearby patient in need.ObjectivesThis study had two objectives: (1) to analyze 10,000 anaphylactic events from the European Anaphylaxis Registry (EAR) by elicitor and location in order to determine typical anaphylactic scenarios and (2) to identify patients’ behavioral and spatial factors influencing their response to ERC emergency requests through a scenario-based survey.MethodsData were collected and analyzed in two phases: (1) clustering 10,000 EAR records by elicitor and incident location and (2) conducting a two-center scenario-based survey of adults and parents of minors with severe allergy who were prescribed EAI, in Israel and Germany. Each group received a four-part survey that examined the effect of two behavioral constructs—shared identity and diffusion of responsibility—and two spatial factors—emergency time and emergency location—in addition to sociodemographic data. We performed descriptive, linear correlation, analysis of variance, and t tests to identify patients’ decision factors in responding to ERC alerts.ResultsA total of 53.1% of EAR cases were triggered by food at patients’ home, and 46.9% of them were triggered by venom at parks. Further, 126 Israeli and 121 German participants completed the survey and met the inclusion criteria. Of the Israeli participants, 80% were parents of minor patients with a risk of anaphylaxis due to food allergy; their mean age was 32 years, and 67% were women. In addition, 20% were adult patients with a mean age of 21 years, and 48% were female. Among the German patients, 121 were adults, with an average age of 47 years, and 63% were women. In addition, 21% were allergic to food, 75% were allergic to venom, and 2% had drug allergies. The overall willingness to respond to ERC events was high. Shared identity and the willingness to respond were positively correlated (r=0.51, P<.001) in the parent group. Parents had a stronger sense of shared identity than adult patients (t243= –9.077, P<.001). The bystander effect decreased the willingness of all patients, except the parent group, to respond (F1,269=28.27, P<.001). An interaction between location and time of emergency (F1,473=77.304, P<.001) revealed lower levels of willingness to respond in strange locations during nighttime.ConclusionsAn ERC allergy app has the potential to improve outcomes in case of anaphylactic events, but this is dependent on patient-peers’ willingness to respond. Through a two-stage process, our study identified the behavioral and spatial factors that could influence the willingness to respond, providing a basis for future research of proximity-based mental health communities.

P031 Systematic-analysis of injection-site pain from administration of subcutaneous adalimumab biosimilar FKB327 versus the adalimumab reference product humira via different methods

BACKGROUND: FKB327 is a proposed biosimilar of the adalimumab reference product (RP). Several studies in both healthy volunteers and patients with active rheumatoid arthritis (RA) were undertaken, the results of which have been reported elsewhere. The formulation excipients of the biosimilar product differ from that of the RP, and different injection-site pain with subcutaneous injection has been reported. The current meta-analysis examines pooled data from these studies in relation to the amount of injection-site pain resulting from using prefilled syringes (PFS) versus auto-injectors (AI) versus regular syringes (RS) and the proposed biosimilar, FKB327, versus the RP. METHODS: Data from 4 studies, FKB327-001, -002, -003, and -004, were pooled in an effort to compare injection-site pain upon subcutaneous administration of FKB327 versus the RP (citrate-containing formulation of the RP (40 mg/0.8 mL). Study FKB327-001, in healthy volunteers (n = 180), involved a single subcutaneous dose of either FKB327 or the RP. Study FKB327-004 was a similar study in healthy Japanese volunteers (n = 130). Study FKB327-002 was a randomized (FKB327 with RS or the RP), double-blind, multiple-dose study in patients with active RA. This was followed by Study FKB327-003, in which patients were rerandomized to receive either FKB327-PFS or the RP in the randomization phase, followed by an open-label extension phase of the study, in which AI was introduced. As patients were continued on treatment or switched during the course of the FKB327-002 and -003 studies, the injection-site pain was assessed at the first dosing occasion of FKB327 or the RP (n = 691). Data from all 4 studies were examined by meta-analysis of the visual analog scale (VAS) using a 100-mm horizontal scale for FKB327 versus the RP and for comparison of AI, PFS, and RS. RESULTS: Data were analyzed from a total of 2007 assessments in 1,001 subjects. A linear mixed model of the VAS in mm for the RP versus FKB327 across all 4 studies showed a 12.6-point improvement in the score for FKB327 versus the RP (95% confidence interval [CI], –14.3 to –10.8; P &lt; 0.001). For the AI and PFS used for FKB327 administration, AI showed a 1.7-point improvement in VAS compared with PFS (95% CI, –3.3 to –0.1; P = 0.035). Gender, age, body weight, and population (healthy subject or patient) were not identified for differences in injection-site pain. CONCLUSION(S): FKB327 showed a significant advantage in terms of injection-site pain compared with the RP, as well as lack of inferiority for both AI and PFS versus RS.

Usability of mepolizumab single-use prefilled autoinjector for patient self-administration

Objective: To evaluate usability of mepolizumab as a liquid drug product self-administered via a single-use prefilled autoinjector (AI) by patients with severe eosinophilic asthma (SEA), or their caregivers, in-clinic and at home.Methods: This open-label, single-arm, Phase IIIa study (NCT03099096; GSK ID: 204959) included patients aged ≥12 years with SEA who were either receiving mepolizumab (100 mg subcutaneously [SC]) every 4 weeks (Q4W) for ≥12 weeks before screening or not receiving mepolizumab but met criteria indicative of SEA. Patients/caregivers self-administered mepolizumab (100 mg SC) via an AI Q4W for 12 weeks. The first (Week 0) and third (Week 8) doses were observed in-clinic; the second dose (Week 4) was administered unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively (determined by investigator/site staff). Patient experience, mepolizumab trough concentrations, blood eosinophil count (BEC), and safety were also assessed.Results: Of 159 patients/caregivers who self-administered ≥1 dose of mepolizumab, 157 completed the study. Nearly all patients successfully self-administered their third mepolizumab dose in-clinic and second dose at home (≥98% and ≥96%, respectively); this was further confirmed by mepolizumab trough concentrations/BEC. At study end, ≥88% of patients were “very” or “extremely” confident about using the AI correctly. Incidence of on-treatment drug-related adverse events (AEs) was low (3%); no fatal AEs occurred.Conclusions: Patients/caregivers successfully self-administered mepolizumab via the AI both in-clinic and at home; no new safety concerns were identified.

Advantages and perspectives of using medicines in the form of auto injectors and prefilled syringes

Today, there is a need to introduce medical devices into everyday medical practice with the goal to self-administer injectional drugs. The speed and safety of auto-injectors / pre-filled syringe pens use (AI/PFS) is the introduction of an injectional form drug in a special medical device, which allows patients to enter a pre-designated therapeutic dose due to the characteristics of the structure of the product, automatic dosing, data of the interactive display on some devices, comfortable design, etc. Considering that AI/PFS were developed to improve the quality of life of patients with various pathological conditions, therefore the creation of affordable medical devices for low-income groups of the population is relevant today. Also an actual issue is the provision of high-quality first-aid kits for soldiers, which is a vital component for medical care in the context of active combat conditions and the lack of the required number of field hospitals.The speed of administration, the onset of effect and ease of use provides significant advantages for AI / PFS. Therefore, the issue of affordability for the low-income groups of the population and the army with the necessary drugs should be sufficiently supported by state regulation.Purpose of study – study of the international experience in the implementation and use of drugs (drugs) in the form of affordable, safe and effective modern dosage forms in the form of autoinjectors.Materials and methods – foreign and domestic literature on the use of AI/PFS in complex and monotherapy treatment of various diseases. State registries of medicines of Ukraine, the USA and some EU countries. The study used systematic, statistical and comparative analyzes, as well as the generalization of information. The data used is freely available among various medical scientific and metric bases, the Internet and international scientific conferences.The analysis of the use of AI/PFS indicates that today the world market of medicines and medical devices contains a large number of drugs under different trade names. However, many patients in the world refrain from using these dosage forms due to the significant cost of medical devices, which makes impossible the required regular use of such drugs for the low-income population groups. This is a significant disadvantage, since AI / PFS is implemented to correct not only chronic diseases such as rheumatoid arthritis, multiple sclerosis, but also to provide emergency careinurgent conditions (anaphylactic reactions, intense pain, etc.).In the global market for drugs and medical devices, injectable medicines in the form of AI/PFS are widely represented. The effectiveness of the use of such devices indicates the advantages and prospects for the use of existing AI/PFS on the global market for patients and medical personnel. Today, the most commonly used drugs in AI/PFSare for the treatment of diabetes, emergency conditions in civil and military medicine, chronic diseases of various etiologies, pediatric practice. The use of AI /PFS significantly improves patient compliance for the treatment of chronic diseases due to ease of use and reduction of adverse reactions at the site of administration. Most of the analyzed sources indicate a low level of economic affordability of drugs in the form of AI/PFS for the population and the government sector of drug supply due to the high cost of the medical devices, compared to traditional syringes. But the results of the study indicate a high level of advantages and prospects in the use of drugs in AI/PFS in medical practice for both medical personnel and patients.

Evidence of bioequivalence and positive patient user handling of a tocilizumab autoinjector

ABSTRACTBackground: The anti–interleukin-6 receptor antibody tocilizumab is approved for subcutaneous injection using a prefilled syringe (PFS). We report results from a bioequivalence study in healthy subjects and a user-handling study in patients with rheumatoid arthritis (RA) using an autoinjector (AI) for tocilizumab.Methods: A randomized crossover study in healthy subjects (N = 161) examined the bioequivalence, safety, and tolerability of tocilizumab after a single subcutaneous injection by AI versus PFS. A nonrandomized observational, real-life human factors study in RA patients (N = 54) assessed user (RA patients, caregivers, health care providers) ability to administer tocilizumab effectively by AI.Results: Bioequivalence criteria for tocilizumab AI versus PFS were met for key pharmacokinetic parameters. Safety was comparable between devices and consistent with the established tocilizumab profile. In the real-life human factors study, the proportion of users who successfully performed all essential tasks required to operate the AI to deliver the full dose was 92.3% at first assessment and 98.1% at second assessment, with no safety concerns.Conclusions: Tocilizumab administration by AI was bioequivalent to administration by PFS. Intended users were successful in performing the tasks required to administer tocilizumab by AI. No new safety signals were observed in either study.Clinical Trial Registration: NCT02678988, NCT02682823

PNS231 THE VALUE OF EMBEDDED INTERVIEWS: CASE STUDY OF QUALITATIVE AND QUANTITATIVE ASSESSMENT OF THE PATIENT EXPERIENCE OF MEPOLIZUMAB SELF-ADMINISTRATION

To describe the value and operational learnings of embedded interviews using mepolizumab trials as a case study. Mepolizumab is licensed to treat severe eosinophilic asthma in the US. Development of a prefilled autoinjector (AI) and prefilled syringe (PFS) has been undertaken to allow self-administration, which may improve the patient treatment experience. Quantitative questionnaires [AI: n=153; PFS: n=56] and complementary qualitative exit interviews [AI: n=25; PFS: n=7] assessing the patient experience of self-injection were embedded in two real-world use studies of mepolizumab administered via an AI [N=159] and PFS [N=56]. • Capturing the patient experience through clinical endpoints alongside quantitative and qualitative patient reported outcomes provided a fuller picture of the value of the mepolizumab AI and PFS. • Qualitative interviews allowed improved interpretation of quantitative results. Example – mepolizumab AI/PFS self-administration studies Primary endpoint • > 99% of injections via both devices were successfully self-administered at week 8. Example of patient treatment experience results • Quantitative (satisfaction): >96% of respondents were “satisfied”/“very satisfied” with using the device (AI/PFS) at home. ○ AI qualitative response example: “… it’s comfortable. I have it at home, I’m independent from anyone else. I can do it any day of the week, any time of the day, and, you know, it’s easy to do. It’s not a big deal”. • Quantitative (convenience): >96% of respondents reported receiving mepolizumab using the device at home (AI/PFS) as “moderately”/”very”/”extremely” convenient. ○ AI qualitative response example: “It’s very convenient, because like I said, you don’t have to leave the house to go to some office in order to get it done”. Operationalisation learnings will allow for implementation improvements of future embedded interviews. Seeking the patient experience can provide valuable additional information. Including qualitative interviews alongside quantitative questionnaires increases response understanding. However, proactive consideration of the operationalisation of embedded interviews is necessary.

GP2017, an adalimumab biosimilar: pharmacokinetic similarity to its reference medicine and pharmacokinetics comparison of different administration methods

ABSTRACT Background: To compare the pharmacokinetics of Sandoz biosimilar adalimumab (GP2017) with reference adalimumab (Humira) in healthy volunteers (PK similarity study) and to compare the pharmacokinetics of GP2017 administered by autoinjector (AI) or prefilled syringe (PFS; delivery study). Methods: Healthy male subjects were randomized to receive a single 40 mg subcutaneous injection of GP2017, US-licensed or EU-authorized reference adalimumab (US/EU-Humira; PK similarity study) or a single 40 mg subcutaneous injection of GP2017 via AI or PFS (delivery study). Pharmacokinetics, safety, and immunogenicity were assessed over 72 days post-injection. Results: The geometric mean ratios (90% confidence intervals) for Cmax and AUC0–inf were 1.05 (0.99–1.11) and 1.04 (0.96–1.13) for GP2017/EU-Humira and 1.00 (0.94–1.06) and 1.08 (1.00–1.18) for GP2017/US-Humira, all within the prespecified margin of 0.80–1.25 (PK similarity study). Pharmacokinetic parameters of GP2017 matched between AI and PFS (delivery study). Safety and immunogenicity were similar across groups in both studies. Conclusion: PK similarity between GP2017, EU- and US-Humira was demonstrated. The safety profile of GP2017 was consistent with previous reports for Humira. These results contribute to the ‘totality-of-the-evidence’ supporting biosimilarity of GP2017 to Humira. PK and tolerability were equivalent for GP2017 dosed by AI or PFS. Trial registration: PK similarity study EudraCT no. 2015-000579-28; Delivery study: EudraCT no. 2014–002879-29

Usability and safety of SB5 (an adalimumab biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis

Objective: To demonstrate comparability between administration of the adalimumab biosimilar, SB5, via prefilled syringe (PFS) and autoinjector (AI) pen based on injection site pain, patient preference, and safety in rheumatoid arthritis (RA) patients.Methods: In this phase 2, open-label study (NCT02565810; EudraCT Number 2014-004887-39), adult RA patients self-administered 40 mg SB5 subcutaneously via PFS at weeks 0 and 2, followed by AI at weeks 4, 6, 8, and 10. Patients rated injection site pain from 0 (no pain) to 10 (severe pain) using a visual numeric scale immediately and 15–30 min post-injection at weeks 0, 2, 4, and 6. Equivalence between PFS and AI was concluded if the 97.5% confidence interval (CI) of the difference in the injection site pain scores at weeks 2 and 6 was contained within the equivalence margin of ±5. Overall impression and preference for PFS and AI were also evaluated. Safety was assessed up to 20 weeks after the first injection.Results: Of 49 patients enrolled, 48 completed the study. Mean injection site pain scores were equivalent between PFS and AI immediately (2.3 vs 2.0; 97.5% CI = −0.99–0.30) and 15–30 min post-injection (0.8 vs 0.7; 97.5% CI = −0.47–0.25). The overall impression of both devices was comparable. The overall preference of AI was higher than PFS. Treatment-emergent adverse events (TEAE) were mild-to-moderate. There were no severe or serious TEAEs reported during the study.Conclusions: In RA patients, SB5 showed equivalent injection site pain and comparable safety when administered via PFS and AI.Trial registration: ClinicalTrials.gov identifier: NCT02565810.

All unexpired Emerade autoinjectors recalled after pens fail to activate

All unexpired Emerade autoinjectors recalled after pens fail to activate

Effects of Iron Fortification on Fatty Acid Profiles of Caprine Milk Cheddar Cheeses under Different Storage Treatment Regimens

Three types of caprine milk Cheddar cheeses as non-fortified control cheese (CC), regular ferrous sulfate (RFS) and large microencapsulated ferrous sulfate (LMFS) fortified cheeses were manufactured in three batches each to evaluate effects of iron addition on fatty acid compositions of two iron fortified cheeses compared to those of CC cheese. All manufactured experimental cheeses were subjected to storage treatments of two temperatures (4 and -18°C) and three periods (0, 2, and 4 months). Fatty acid profiles of the experimental cheeses were quantified using a gas chromatograph equipped with a fused silica capillary column, flame ionization detector, AOC-20s auto sampler and AOC-20i auto injector. Results showed that cheese type significantly (p<0.05 or p<0.01) affected levels of most fatty acids, except for C10:0, C14:1, C16:1, C18:1, and C20:0 acids, indicating that fatty acid contents of iron fortified cheeses were generally higher than control cheese especially at 4 months of storage. The level of C16:0 was highest, followed by C18:1, C18:0 and C10:0 acid, respectively, in all three types of the experimental goat milk cheeses for all storage treatment regimens. The main factors of cheese type, storage temperature and time had significant influences on several different fatty acids, and some of the 2-way and 3-way interactions also showed significant effects on levels of different fatty acids. It was concluded that iron fortification, storage temperature and period had significant influences on the levels of majority of tested fatty acids in the experimental caprine milk Cheddar cheeses.

Use of Auto-Injector for Methotrexate Subcutaneous Self-Injections: High Satisfaction Level and Good Compliance in SELF-I Study, a Randomized, Open-Label, Parallel Group Study

IntroductionThe objective of the study was to compare compliance and acceptability of a new auto-injector (AI) versus syringe for administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA).MethodsWe conducted a randomized, open-label, parallel group study comparing AI to pre-filled syringe (PFS). Adult patients with RA (ACR/EULAR 2010) receiving MTX (orally or by injection) for at least 3 months were allocated to AI or PFS for 6 months and then were allocated to AI for 6 further months. Two co-primary endpoints were defined at M6: percentage of patients with compliance at least 80%; change in functional capacity assessed by Health Assessment Questionnaire (HAQ). Secondary endpoints included quality of life (RaQoL), RA activity (DAS28), and acceptability. Local safety at injection site was assessed at each visit.ResultsTwo-hundred and sixty-five patients were randomized. The main analysis was conducted on per protocol set (99 AI and 98 PFS). Compliance was 96.2% in AI and 98.9% in PFS. Good complier rates were 89.9% and 94.9%, thus a difference of − 5.0% (− 18.9%; 8.9%). HAQ remained stable in both groups. No difference was found on RaQoL, change in RA activity, and safety profile. Autonomy, acceptability, and patient satisfaction were better with AI, and patients having had the experience of both AI and PFS preferred AI (p < 0.001).ConclusionsAlthough this study did not demonstrate non-inferiority of AI versus PFS, compliance was excellent in the two groups, and AI, which was preferred by patients, is a valuable alternative to PFS for administration of MTX.Trial RegistrationClinicalTrials.gov identifier, NCT02553018.FundingNordic Pharma SAS.

Opioid overdose response training in pharmacy education: An analysis of students’ perception of naloxone use for opioid overdose prevention

Background and purposePharmacists in New Mexico have prescriptive authority to prescribe naloxone. However, no formal naloxone training has been provided for students at the University of New Mexico College of Pharmacy. Educational activity and settingTraining was incorporated into a pharmaceutical care laboratory course. First-year (P1) (n = 63) and third-year (P3) (n = 78) pharmacy students were asked to answer a pre- and post-training survey. The survey was designed to assess students’ self-rated knowledge, clinical-type skills related to naloxone and opioids, and attitude toward prescribing naloxone. In class students reviewed the epidemiology of opioid overdose and risk assessment methods for patients, and the students practiced using an intranasal spray and an auto injector. FindingsThe pre-survey showed that P3 students had higher confidence levels in regards to naloxone therapy compared with P1 students. However, educational materials significantly increased confidence levels in drug knowledge, clinical-type skills, and patient counseling in both cohorts. The P3 cohort tended to be more likely to disagree with advertisements about the availability of naloxone therapy by pharmacists as compared to the P1 cohort. SummaryP1 and P3 students demonstrated improved knowledge, skills, and attitudes in regards to naloxone therapy and dispensing. Naloxone training is essential to increase pharmacy students’ knowledge about opioid overdose and naloxone benefits. Although the training helped increase students’ confidence level, additional practical training and longitudinal instruction in a pharmacy curriculum would be valuable so that students could transfer the knowledge into practice as a pharmacist.

Erratum.

EpilepsiaVolume 59, Issue 12 p. 2344-2344 ERRATUMFree Access Erratum This article corrects the following: A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures Bassel Abou-Khalil, James Wheless, Joanne Rogin, Kevin D. Wolter, Glenn C. Pixton, Rajesh B. Shukla, Nancy A. Sherman, Kenneth Sommerville, Veeraindar Goli, Carl L. Roland, Volume 54Issue 11Epilepsia pages: 1968-1976 First Published online: September 20, 2013 First published: 19 November 2018 https://doi.org/10.1111/epi.14616AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In 1, the National Clinical Trial (NCT) number was omitted from the article abstract. Below is the article abstract updated to include the NCT number. We apologize for this error. Abstract Purpose: A diazepam auto-injector (AI) has been developed for intramuscular administration to treat acute repetitive seizures (ARS). The objective of this study was to evaluate the efficacy and safety of the diazepam AI when administered by caregivers to control an episode of ARS (ClinicalTrials.gov identifier NCT00319501). Methods: In this phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter study, subjects with epilepsy on a stable antiepileptic drug regimen who required intermittent medical intervention to control ARS were randomized 1:1 to the placebo AI or the diazepam AI group. Subjects were stratified according to age (2–5, 6–11, ≥12 years). Dose (5, 10, 15, or 20 mg) was based on age and weight. A single dose of study medication was dispensed to be administered by caregivers in an outpatient setting when required. The primary end point was time to next seizure or rescue from 15 min to 12 h postdose. Secondary end points included rescue medication use, number of seizures postdose, caregiver and physician treatment assessments, and safety measures. Key findings: Of 234 subjects randomized, 81/110 in the placebo AI group and 82/124 in the diazepam AI group were included in the intent-to-treat analysis. Baseline characteristics were similar for both groups. Time to next seizure or rescue was significantly longer in the diazepam AI group compared with the placebo AI group, with a hazard ratio of 0.55 (95% confidence interval [CI] 0.34–0.88; p = 0.012) for diazepam AI versus placebo AI, adjusted for age group. The 25th percentile for time to the next seizure or rescue was 1.18 h (95% CI 0.38–2.03) for placebo AI and 2.70 h (95% CI 0.48–11.42) for diazepam AI; the median was 5.9 h for placebo AI and was inestimable for diazepam AI due to the low number of events experienced by subjects in that group. The proportion of subjects using rescue medication postdose was 30% (24/81) placebo AI versus 17% (14/82) diazepam AI (p = 0.066). An event (seizure or rescue) occurred in 55.6% of subjects in the placebo AI group and 35.4% in the diazepam AI group. The number of seizures experienced during the 12-h postdose period was significantly lower for diazepam AI (median 0.0) compared with placebo AI (median 1.0; p = 0.010). Treatment-emergent adverse events (TEAEs) were reported in 44% (35/79) of subjects in the placebo AI group and 42% (34/81) in the diazepam AI group. The most common TEAEs reported were injection site pain (15% placebo AI, 17% diazepam AI) and injection site hemorrhage (6% placebo AI, 5% diazepam AI). Significance: The diazepam AI was significantly more effective than placebo AI at delaying the next seizure or rescue. Secondary efficacy end points were generally supportive of the primary outcome. Diazepam AI administered by trained caregivers was effective for the treatment of ARS and was well tolerated, with a safety profile similar to placebo. Reference 1Abou-Khalil B, Wheless J, Rogin J, et al. A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures. Epilepsia. 2013; 54: 1968– 76. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume59, Issue12December 2018Pages 2344-2344 ReferencesRelatedInformation

Comparison of practical application steps of the previously used adrenaline auto injector in Turkey (EpiPen) and the currently available adrenaline auto injector (Penepin): a multi-center study.

It has been shown by a great number of studies that the correct use of adrenaline auto injectors prescribed to patients with anaphylaxis is associated with the design of the auto injector, in addition to training. The aim of this study was to compare the skills of adults in using two different auto injectors prescribed to patients with anaphylaxis. Parents of patients aged between 1 and 18 years who referred to allergy outpatients were included in the study. A total of 630 volunteers from nine centers were included in the study. Four hundred fifty-seven (72.5%) of the participants were females and 235 (37.3%) were undergraduates. The rate of showing all the steps of auto injector trainers correctly by the participants was found as (60.2%) (n=379) for EpiPen and 42.9% (n=270) for Penepin (p<0.001). The most frequent mistake with both auto injector trainers was the step of "place appropriate injection tip into outer thigh/press the trigger so it clicks." When the preferences of the volunteers were asked after training and application, 527 (83.7%) chose EpiPen, stating that it was easier and simpler to use. Our study showed that the correct usage rates of both adrenaline auto injectors were much lower than expected and there could be mistakes in the application of both. It could be appropriate to make improvements in the design of Penepin, which is still the only available adrenaline auto injector in Turkey, such that its application steps will be simpler and quicker.

The composition of nonbeverage alcohols consumed in Russia in 2015–2017

Introduction From previous research it is known that nonbeverage alcohols (NAs) were consumed by significant proportions of Russian population for drinking (e.g. 7% of working age males). In illegal NAs spirits other than ethanol may be used for their manufacturing. Such cases of illegal production from time to time manifest in outbreaks of deadly alcohol poisonings. The most recent such outbreak occurred in December 17–26 2016 in the Siberian city of Irkutsk, where 123 people, who drunk spirituous bath additive “Hawthorn” containing admixture of methanol, were poisoned, of whom 76 died. In a previous study conducted in 2005 NAs typically contained rectified highly concentrated ethanol. However, the study was conducted more than a decade ago and on a relatively small number of samples purchased only in one region of Russian Federation. To provide most up to date information on the problem we conducted a study of composition of NAs, which were available in retail in cities across the vast geography of Russia. Methods For analysis of composition we selected 92 samples of NAs, which were purchased in a survey of NAs availability in 50 Russian cities between 2015 and 2017. Consumption for drinking of selected types of NAs has been confirmed in simultaneous survey of subjects with substance use disorders recruited in narcology clinic in Kazan, Russia in 2015–2017. Gas chromatography and mass spectrometry (GC-MS) on a Hewlett-Packard 7820A gas chromatograph were used to determine NAs composition. For detection of extractable organic components we employed a method of micro extraction in a vial. For this purpose nonbeverage alcohol, internal standard and extragent were aliquoted to a standard vial for auto injector. After extraction of organic compounds inside the vial in a vibro shaker and separation of organic layer the later was taken for GC-MS analysis. The literature on toxicity of identified admixtures was reviewed. Results The majority of NAs contained 60 v/v% or more ethanol and represented either pure solutions of ethanol without other admixtures, or contained specific active ingredients. The following substances were identified in significant amounts in some of the analysed samples: –eau-de-colognes and some lotions consumed for drinking (e.g. Troynoi, Shipr, Ogurechniy, Hawthorn): propylene glycol and polypropylene glycols (e.g. dypropylene glycol), phenylethyl alcohol, linalyl anthranilate, ethyl salicylate, diphenyl ether; butylated hydroxytoluene, 3-phenyl-2-butanol, benzenemethanol, cyclamal, lilyal, and other substances; –cosmetic lotions: diethyl phthalate; –antiseptics: formic acid; –medicinal tinctures: compounds of plant extracts. Some medicinal tinctures sold in 100 ml bottles and cosmetic lotions didn’t contain active substances (e.g. capsaicin, flavouring agents, plant extracts). Conclusions On some identified compounds (e.g. 3,3′-oxybis-2-butanol; lilyal, etc.) limited or no human toxicity data is available, especially when ingested. Propylene glycols, although classed as substances with low toxicity, when ingested in large amounts may cause metabolic acidosis, cardiac arrhythmias and even cardiac arrest. Antiseptic containing 1.4% solution of formic acid in 70% ethanol when swallowed may cause multiple toxic effects of various severities, depending on amount consumed. These include gastrointestinal mucous burns, ulcerations, and bleeding; circulatory collapse, renal failure, ischemic lesions in liver and heart; late oesophageal, gastric and pyloric stenosis; asphyxial death due to glottic oedema, or due to toxic shock among others. Absence of active substances in some NAs suggests their illegal nature. Control of NAs production and consumption in Russia must be a priority as toxicity of some of them is determined not only by cheap concentrated ethanol, but also by other toxic admixtures. More toxicological research is needed on interaction of various compounds of NAs with ethanol and its metabolites.

Similar Pharmacokinetics of the Adalimumab (Humira®) Biosimilar BI 695501 Whether Administered via Subcutaneous Autoinjector or Prefilled Syringe (VOLTAIRE®-AI and VOLTAIRE®-TAI): Phase 1, Randomized, Open-Label, Parallel-Group Trials.

IntroductionBI 695501 has shown similar efficacy, safety, and immunogenicity to the adalimumab reference product, Humira®. We present two phase 1 studies comparing the pharmacokinetics, safety, and immunogenicity of BI 695501 delivered via autoinjector (AI) vs. prefilled syringe (PFS).MethodsBoth trials were randomized, open-label, parallel-group studies undertaken in subjects aged ≥ 18–65 years. VOLTAIRE®-AI (NCT02606903) recruited healthy, Caucasian, male, non-athletic volunteers with BMI ≥ 18 to ≤ 30 kg/m2. VOLTAIRE®-TAI (NCT02899338) recruited healthy men and women with BMI > 17.5 to < 35 kg/m2. In both studies, a single dose of BI 695501 40 mg was administered via AI or PFS to the abdomen (VOLTAIRE®-AI) or thigh (VOLTAIRE®-TAI). The observation period was 43/57 days and the safety follow-up was 70 days. Co-primary endpoints were AUC0–1032 or AUC0–1368, Cmax, and AUC0–∞. Safety and immunogenicity were assessed.ResultsSubjects (VOLTAIRE®-AI: N = 71; VOLTAIRE®-TAI: N = 162) were randomized to AI (n = 35; n = 81) or PFS (n = 36; n = 81). Baseline characteristics were balanced between treatment groups in each study. Total exposure of BI 695501 was similar for both groups; adjusted geometric mean ratios for AUC0–∞, AUC0–1032, and Cmax were 106.17, 104.09, and 114.83%, respectively, for VOLTAIRE®-AI; 103.19, 101.71 (AUC0–1368), and 100.11% for VOLTAIRE®-TAI. In both studies, similar immunogenicity was observed between groups in terms of frequency of binding and neutralizing anti-drug antibody-positive subjects. Incidence of adverse events was similar for both groups.ConclusionsPharmacokinetics and immunogenicity of BI 695501 delivered via AI were similar to administration using a PFS, independent of injection site. No differences are expected between AI and PFS use in clinical practice.FundingBoehringer Ingelheim.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0119-1) contains supplementary material, which is available to authorized users.

Successful administration of BI 695501, an adalimumab biosimilar, using an autoinjector (AI): results from a Phase II open-label clinical study (VOLTAIRE®-RL)

ABSTRACTBackground: This study examined the patient handling experience and self-injection success of patients with rheumatoid arthritis (RA) administering BI 695501 using an AI.Methods: This Phase II, 7-week, open-label, interventional study (NCT02636907) included adult patients with moderately to severely active RA not adequately controlled by DMARDs, with no experience of self-injecting with AI/pen. Patients self-injected BI 695501 via AI every 2 weeks in the AI Assessment Period (AAP). Training was given on first injection; AI handling events were recorded. Percentage of self-injection success was the primary end point. Patients could enter a 42-week pre-filled syringe (PFS) safety extension.Results: The AAP was completed by 73/77 patients. In total, 216/218 (99.1%) self-injections on Days 15, 29, and 43, were successful. Nine (11.7%) patients had drug-related adverse events (AEs). Two patients reported four serious AEs (SAEs), none drug-related. Overall (in the AAP and PFS extension), 28 (36.4%) patients had drug-related AEs; nine patients had SAEs, one was considered drug-related. Five (6.5%) patients reported injection-site reactions in the AAP; 13 (18.1%) in the PFS extension.Conclusions: After training, almost all patients were successfully able to self-administer BI 695501 using an AI. BI 695501 via AI (and via PFS in the extension) was well tolerated.Clinical Trial Registration: NCT02636907

School Based Health Care Program Provides Epinephrine Auto Injector Prescription and Training In Schools

PROGRAM: On April 21, 2014, Ohio Governor John Kasich signed House Bill (HB) 296 into law permitting schools to procure non-individual specific Epinephrine Auto Injectors (EAI) for use in emergency anaphylaxis. Participating schools must adopt a policy governing use and maintenance, written in collaboration with a licensed health professional who is authorized to prescribe. Our School Based Health Care Program (SBHC) aims to team up and collaborate with schools to provide a prescription for minimum of two EAI per school with multiple refills for 1 year, assists in developing the …

School Based Health Care Program Provides Epinephrine Auto Injector Prescription and Training In Schools

School Based Health Care Program Provides Epinephrine Auto Injector Prescription and Training In Schools