NTNU Intranasal Naloxone Trial (NINA-1) Study documentsdoi:10.18710/ABRUWWDataverseNO2020-04-232Skulberg, Arne Kristian; Dale, Ola, 2020, "NTNU Intranasal Naloxone Trial (NINA-1) Study documents", https://doi.org/10.18710/ABRUWW, DataverseNO, V2NTNU Intranasal Naloxone Trial (NINA-1) Study documentsDouble blinded, double dummy, randomised controlled trial of intranasal naloxone for pre- hospital useEudraCT Number: 2016-004072-22doi:10.18710/ABRUWWNCT03518021Skulberg, Arne KristianDale, OlaSkulberg, Arne KristianDale, OlaBraarud, Anne-CathrineDale, JosteinTylleskar, IdaHeyerdahl, FridtjofSkålhegg, ToreBarstein, JanNTNU – Norwegian University of Science and TechnologyDataverseNONTNU – Norwegian University of Science and TechnologySkulberg, Arne KristianSkulberg, Arne Kristian2020-04-13Medicine, Health and Life SciencesNaloxoneAdministration, IntranasalInjections, IntramuscularNarcotic AntagonistsDrug OverdoseRandomized Controlled Trials as TopicVulnerable PopulationsConsent FormsThis section contains study documents forming the basis of the NINA-1 Trial.
Documents will be added at Sponsors discretion, and aim to reflect the Trial Master File. Please consult the file 00readme for a key to how documents are coded in this dataset.
If you have any specific document you would like access to, please contact us, and Sponsor will consider publication.
Some documents will be altered to facilitate open publication. In such case this will be clearly marked.
All documents are combined with approved translations into English and original document in Norwegian where necessary.
The NINA-1 Trial is a phase 3 drugs trial of nasal naloxone. It is double-blinded, double dummy, randomised controlled trial, two-centre study, non-inferiority design. The centres are Oslo University Hospital and St Olav’s Hospital, University Hospital of Trondheim. As we compare two different routes of administration, a dummy design is needed to blind the ambulance crew for the intervention.
This means patients will receive a nasal spray and an intramuscular injection simultaneously, randomised for one to contain the antidote naloxone, the other inactive sterile saline solution. It is designed and powered to be a non-inferiority study with an estimated 200 participants to be included.
The primary endpoint is the proportion of participants with return of spontaneous respiration (≥10 breaths per minute) within 10 minutes of naloxone administration. The aim is to demonstrate that intranasal administration of naloxone is not clinically inferior to intramuscular administration. It is expected that 88% of the patients on IM treatment will be responders and an equivalent dose intranasal administration is expected to result in a similar responder rate. The non-inferiority margin
is set at Δ=0.15. The null hypothesis is that the proportion of responders given intranasal naloxone is smaller than given intramuscular naloxone.Elements from Trial Master File of NINA-1 file. Study documents relating to protocol, approvals, information, funding, statistics and other.Skulberg AK, Asberg A, Khiabani HZ, Rostad H, Tylleskar I, Dale O. Pharmacokinetics of a novel, approved, 1.4-mg intranasal naloxone formulation for reversal of opioid overdose-a randomized controlled trial. Addiction 2019; 114(5): 859-67.10.1111/add.14552Skulberg AK, Asberg A, Khiabani HZ, Rostad H, Tylleskar I, Dale O. Pharmacokinetics of a novel, approved, 1.4-mg intranasal naloxone formulation for reversal of opioid overdose-a randomized controlled trial. Addiction 2019; 114(5): 859-67.Skulberg AK, Tylleskar I, Valberg M, Braarud AC, Dale J, Heyerdahl F, et al. Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial. Addiction. 2022;117(6):1658-67.doi.org/10.1111/add.15806Skulberg AK, Tylleskar I, Valberg M, Braarud AC, Dale J, Heyerdahl F, et al. Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial. Addiction. 2022;117(6):1658-67.Skulberg AK, Tylleskar I, Nilsen T, et al. Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers. Eur J Clin Pharmacol 2018; 74(7): 873-83.10.1007/s00228-018-2443-3Skulberg AK, Tylleskar I, Nilsen T, et al. Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers. Eur J Clin Pharmacol 2018; 74(7): 873-83.Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Dale O. Naloxone nasal spray - bioavailability and absorption pattern in a phase 1 study. Tidsskr Nor Laegeforen 2019; 139(13).10.4045/tidsskr.19.0162Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Dale O. Naloxone nasal spray - bioavailability and absorption pattern in a phase 1 study. Tidsskr Nor Laegeforen 2019; 139(13).Tylleskar I, Skulberg AK, Skarra S, Nilsen T, Dale O. Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil. Eur J Clin Pharmacol 2018; 74(12): 1547-53.10.1007/s00228-018-2545-yTylleskar I, Skulberg AK, Skarra S, Nilsen T, Dale O. Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil. Eur J Clin Pharmacol 2018; 74(12): 1547-53.Madah-Amiri D, Skulberg AK, Braarud A-C, et al. Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility. Subst Abus 2018; Online 27 Jun 2018.: 1-6.10.1080/08897077.2018.1485130Madah-Amiri D, Skulberg AK, Braarud A-C, et al. Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility. Subst Abus 2018; Online 27 Jun 2018.: 1-6.Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Jansook P, Dale O. Pharmacokinetics of a new, nasal formulation of naloxone. Eur J Clin Pharmacol 2017; 73(5): 555-62.10.1007/s00228-016-2191-1Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Jansook P, Dale O. Pharmacokinetics of a new, nasal formulation of naloxone. Eur J Clin Pharmacol 2017; 73(5): 555-62.00readme-1.txtConsult this document for easier access to specific documentstext/plain01_1_NINA-1_Study_protocol-version_3_3.pdfapplication/pdf01_2_NINA-1_Study_protocol-version_1.pdfThis first trial protocol was not approved by Norwegian Medicines Agency. No participants included in the trial under this protocolapplication/pdf01_2_NINA-1_Study_protocol-version_2.pdfThis protocol version was valid prior to the inclusion of the first patient. No participants included in the trial under this protocolapplication/pdf01_2_NINA-1_Study_protocol-version_3_0.pdfapplication/pdf01_2_NINA-1_Study_protocol-version_3_1.pdfapplication/pdf01_2_NINA-1_Study_protocol-version_3_2.pdfapplication/pdf01_3_NINA-1_SPIRIT2013_33_item_checklist.pdfStandard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2013)
This statement provides evidence for the minimum content of the NINA-1 trial protocol as outlined by SPIRITapplication/pdf02_NINA-1_IB_version_7_March2020.pdfINVESTIGATOR’S BROCHURE
PRODUCT: Nalokson DnE Nasal Spray 14 mg/mLapplication/pdf03_1_NINA-1_informed_consent_forms .pdfExample informed consent information forms from study kit and online versionapplication/pdf04_1_NINA-1_Annual_Safety_Report_NoMA_2018_19.pdfAnnual Safety reports submitted to Norwegian Medicines Agency application/pdf04_2_NINA-1_Data_monitoring_committee_reports .pdfapplication/pdf04_3_NINA-1_Data_monitoring_committee_charter .pdfapplication/pdf05_1_NINA-1_ Insurance_statements.pdfapplication/pdf05_3_NINA-1_Financing_Contract_NTNU_FarmaIndusriAS.pdfAgreements between NTNU and Farma Industri governing the funding of Study Medicine and ensuring NTNU full ownership of trial results.application/pdf05_3_NINA-1_Financing_Regional_Health_Authority(EN_NO).pdfFinancing for PhD position for Arne Skulberg supervised by Prof. Ola Dale and main funding for NINA-1application/pdf06_1_NINA-1_National_Ethics_Approval_March_2017_(EN_NO).pdfTrial approval and review by The National Committee for Medical and Health Research Ethics (NEM) in Norwayapplication/pdf06_1_NINA-1_Regional_Ethics_Approval_March_2020(EN_NO).pdfApproval of protocol version 3.3 06. March 2020 by The Regional Committee for Medical and Health Research Ethics (REC) in Norwayapplication/pdf06_1_NINA-1_Regional_Ethics_Approval_Oct_2017(EN_NO).pdfApproval of protocol NINA-1 trial by The Regional Committee for Medical and Health Research Ethics (REC) in Norwayapplication/pdf06_2_NINA-1_First_trial_approval_NoMA_December_2017.pdfOriginal approval by The Norwegian Medicines Agencyapplication/pdf06_2_NINA-1_Protocol_v_3_3_approval_NoMA_March_2020.pdfApproval by Norwegian Medicines Agency protocol amendments version 3.3 dated 6th March 2020application/pdf09_1_NINA-1_Monitoringplan.pdfapplication/pdf09_2_NINA-1_Monitoring_reports_Oslo.pdfapplication/pdf09_2_NINA-1_Monitoring_reports_Trondheim.pdfapplication/pdf10_1_NINA-1_Case_report_form.pdfExample Case Report from from study kitapplication/pdf10_1_NINA-1_Serius_Adverse_event-form.pdfExample Serious Adverse Event form from study kitapplication/pdf12_1 _NINA-1_Data_management_plan.pdfapplication/pdf12_2_NINA-1_Data_managment_report.pdfapplication/pdf12_3 _NINA-1_Database_lock_documentation.pdfapplication/pdf13_1_NINA-1_Statistical_Analysis_Plan.pdfThe first, and final, Statistical Analysis Planapplication/pdf