{ "resourceType" : "Composition", "id" : "568060", "meta" : { "versionId" : "5", "lastUpdated" : "2026-06-22T14:51:09.037Z", "profile" : ["http://hl7.org/fhir/uv/ebm/StructureDefinition/m11-report-section-03"] }, "language" : "en", "text" : { "status" : "additional", "div" : "
" }, "extension" : [{ "url" : "http://hl7.org/fhir/StructureDefinition/artifact-description", "valueMarkdown" : "Example of M11ReportSection03 Profile" }, { "url" : "http://hl7.org/fhir/uv/ebm/StructureDefinition/artifact-publication-status", "valueCodeableConcept" : { "coding" : [{ "system" : "http://terminology.hl7.org/CodeSystem/cited-artifact-status-type", "code" : "active", "display" : "Active" }] } }], "url" : "https://fevir.net/resources/Composition/568060", "identifier" : [{ "type" : { "coding" : [{ "system" : "http://terminology.hl7.org/CodeSystem/v2-0203", "code" : "ACSN", "display" : "Accession ID" }], "text" : "FEvIR Object Identifier" }, "system" : "https://fevir.net/FOI", "value" : "568060", "assigner" : { "display" : "Computable Publishing LLC" } }], "status" : "final", "type" : { "coding" : [{ "system" : "http://loinc.org", "code" : "35528-9", "display" : "Clinical trial protocol Clinical trial protocol" }], "text" : "CeSHarP Report" }, "category" : [{ "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218526", "display" : "ICH M11 Protocol Section 3 TRIAL OBJECTIVES AND ASSOCIATED ESTIMANDS" }], "text" : "section3-estimands" }], "subject" : [{ "reference" : "ResearchStudy/267245", "type" : "ResearchStudy", "display" : "A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example" }], "date" : "2026-06-22T14:51:09.037Z", "author" : [{ "display" : "Brian S. Alper, MD, MSPH" }], "title" : "M11 Report Section 3 (Trial Objectives and Associated Estimands) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example", "custodian" : { "reference" : "Organization/118079", "type" : "Organization", "display" : "Computable Publishing LLC" }, "relatesTo" : [{ "type" : "derived-from", "targetReference" : { "reference" : "ResearchStudy/267245", "type" : "ResearchStudy", "display" : "A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example" } }, { "type" : "cite-as", "targetMarkdown" : "M11 Report Section 3 (Trial Objectives and Associated Estimands) for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus - M11 Example [Database Entry: FHIR Composition Resource]. Contributors: Brian S. Alper, MD, MSPH [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 568060. Revised 2026-06-22. Available at: https://fevir.net/resources/Composition/568060. Computable resource at: https://fevir.net/resources/Composition/568060#json." }], "section" : [{ "title" : "3 TRIAL OBJECTIVES AND ASSOCIATED ESTIMANDS", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218526", "display" : "ICH M11 Protocol Section 3 TRIAL OBJECTIVES AND ASSOCIATED ESTIMANDS" }], "text" : "section3-estimands" }, "text" : { "status" : "empty", "div" : "

[No data.]

" }, "section" : [{ "title" : "3.1 Primary Objective(s) and Associated Estimand(s)", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218527", "display" : "ICH M11 Protocol Section 3.1 Primary Objective(s) and Associated Estimand(s)" }], "text" : "3.1-Primary-Objective(s)-and-Associated-Estimand(s)" }, "text" : { "status" : "empty", "div" : "

[No data.]

" }, "section" : [{ "title" : "3.1.1 Primary Objective 1", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218528", "display" : "ICH M11 Protocol Section 3.1.1 Primary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-primaryOutcome-0", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia (NCT03421379)" }, "text" : { "status" : "additional", "div" : "

Primary objective label: Treatment success

Primary objective description:To demonstrate that 3 mg LY900018 is non-inferior to 1 mg IMG for the proportion of patients achieving treatment success from insulin-induced hypoglycemia using a non-inferiority margin of 10%

TypePrimary
PopulationStudy Population.
TreatmentGlucagon Nasal Powder (Experimental)
TreatmentGlucagon Hydrochloride Solution (Active Comparator)
Endpoint

Proportion achieving treatment success

Endpoint title: Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia (NCT03421379)

Outcome description: The proportion of patients achieving treatment success defined as either an increase in PG to >70 mg/dL or an increase of >20 mg/dL from nadir within 30 minutes after administration of glucagon. The nadir is defined as the minimum PG value at the time of or within 10 minutes following glucagon administration.

Population-level Summaryrisk difference
" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-primaryOutcome-0", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia (NCT03421379)" }, { "reference" : "Group/267506", "type" : "Group", "display" : "M11 IGBJ Protocol Example Eligibility Criteria" }, { "reference" : "Group/370701", "type" : "Group", "display" : "Glucagon Nasal Powder (Experimental)" }, { "reference" : "Group/370702", "type" : "Group", "display" : "Glucagon Hydrochloride Solution (Active Comparator)" }] }] }, { "title" : "3.2 Secondary Objective(s) and Associated Estimand(s)", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218529", "display" : "ICH M11 Protocol Section 3.2 Secondary Objective(s) and Associated Estimand(s)" }], "text" : "3.2-Secondary-Objective(s)-and-Associated-Estimand(s)" }, "text" : { "status" : "additional", "div" : "
" }, "section" : [{ "title" : "3.2.1 Secondary Objective 1", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "display" : "serious adverse events (SAEs)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: Safety and tolerability

Secondary objective description: To compare the safety and tolerability of 3 mg LY900018 with 1 mg IMG

Estimand CharacteristicDescription
Endpoint

serious adverse events (SAEs)

" }, "entry" : [{ "display" : "serious adverse events (SAEs)" }] }, { "title" : "3.2.1 Secondary Objective 2", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "display" : "treatment-emergent adverse events (TEAEs)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: Safety and tolerability

Secondary objective description: To compare the safety and tolerability of 3 mg LY900018 with 1 mg IMG

Estimand CharacteristicDescription
Endpoint

treatment-emergent adverse events (TEAEs)

Outcome description: treatment-emergent adverse events (TEAEs) (including gastrointestinal, nasal, and non-nasal AEs)

" }, "entry" : [{ "display" : "treatment-emergent adverse events (TEAEs)" }] }, { "title" : "3.2.1 Secondary Objective 3", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "display" : "vital signs" }, "text" : { "status" : "generated", "div" : "
Estimand CharacteristicDescription
Endpoint

vital signs

" }, "entry" : [{ "display" : "vital signs" }] }, { "title" : "3.2.1 Secondary Objective 4", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-0", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) (NCT03421379)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: To characterize the PK profile of 3 mg LY900018 compared to 1 mg IMG

Secondary objective description: PK parameters include AUC, Cmax, Tmax PD parameters include BGmax and Tmax

Estimand CharacteristicDescription
Endpoint

Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) (NCT03421379)

" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-0", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM) (NCT03421379)" }] }, { "title" : "3.2.1 Secondary Objective 5", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-1", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }, "text" : { "status" : "generated", "div" : "
Estimand CharacteristicDescription
Endpoint

PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)

" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-1", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }] }, { "title" : "3.2.1 Secondary Objective 6", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-2", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: To characterize the PK profile of 3 mg LY900018 compared to 1 mg IMG

Secondary objective description: PK parameters include AUC, Cmax, Tmax PD parameters include BGmax and Tmax

Estimand CharacteristicDescription
Endpoint

Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)

" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-2", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }] }, { "title" : "3.2.1 Secondary Objective 7", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-3", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: To characterize the PK profile of 3 mg LY900018 compared to 1 mg IMG

Secondary objective description: PK parameters include AUC, Cmax, Tmax PD parameters include BGmax and Tmax

Estimand CharacteristicDescription
Endpoint

PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)

" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-3", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }] }, { "title" : "3.2.1 Secondary Objective 8", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218530", "display" : "ICH M11 Protocol Section 3.2.1 Secondary Objective" }] }, "focus" : { "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-4", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }, "text" : { "status" : "additional", "div" : "

Secondary objective label: To characterize the PK profile of 3 mg LY900018 compared to 1 mg IMG

Secondary objective description: PK parameters include AUC, Cmax, Tmax PD parameters include BGmax and Tmax

Estimand CharacteristicDescription
Endpoint

PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)

" }, "entry" : [{ "type" : "EvidenceVariable", "identifier" : { "type" : { "text" : "FEvIR Linking Identifier" }, "system" : "https://fevir.net/FLI", "value" : "NCT03421379-secondaryOutcome-4", "assigner" : { "display" : "Computable Publishing LLC" } }, "display" : "PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM (NCT03421379)" }] }] }, { "title" : "3.3 Exploratory Objective(s)", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218531", "display" : "ICH M11 Protocol Section 3.3 Exploratory Objective(s)" }], "text" : "3.3-Exploratory-Objective(s)" }, "text" : { "status" : "additional", "div" : "
" }, "section" : [{ "title" : "3.3.1 Exploratory Objective 1", "code" : { "coding" : [{ "system" : "http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl", "code" : "C218532", "display" : "ICH M11 Protocol Section 3.3.1 Exploratory Objective" }] }, "focus" : { "display" : "Presence of anti-glucagon antibodies" }, "text" : { "status" : "additional", "div" : "

\u00a0

\n
\n
Exploratory Objectives\n

Description Explore the formation of anti-glucagon antibodies to glucagon

\n

Outcome Measures:

\n

Unnamed outcome measure

\n \n \n \n \n \n \n \n
EndpointPresence of anti-glucagon antibodies

\u00a0 \u00a0

\n

Name: To evaluate the recovery from clinical symptoms of hypoglycemia

\n

Description Hypoglycemia symptoms questionnaire

" }, "entry" : [{ "display" : "Presence of anti-glucagon antibodies" }] }] }] }] }