{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05525416","title":"Sex Differences in Sympathetic Vascular Reactivity at High Altitude","sponsor":"University of Alberta","phases":["NA"],"status":"COMPLETED","indication":null,"disease":"cold-induced vasodilation"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of GUCY1B1, GUCY1A2, GUCY1A1, ADRA1A, ADRA1D, ADRA1B, ADRA2A, ADRB1, ADRB2 has somatic-mutation evidence in cold-induced vasodilation","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: GUCY1B1 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000061918/EFO_0803534","date":"2026-11-11T22:45:33.812Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for GUCY1B1, GUCY1A2, GUCY1A1, ADRA1A, ADRA1D, ADRA1B, ADRA2A, ADRB1, ADRB2 in cold-induced vasodilation","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: GUCY1B1 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000061918/EFO_0803534","date":"2026-11-11T22:45:33.812Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"no","detail":"Not on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"GUCY1B1 (via Sodium Nitroprusside)","text":"Open Targets has no association between GUCY1B1 and cold-induced vasodilation.","source":{"label":"Open Targets: GUCY1B1 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000061918/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"GUCY1A2 (via Sodium Nitroprusside)","text":"Open Targets has no association between GUCY1A2 and cold-induced vasodilation.","source":{"label":"Open Targets: GUCY1A2 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000152402/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"GUCY1A1 (via Sodium Nitroprusside)","text":"Open Targets has no association between GUCY1A1 and cold-induced vasodilation.","source":{"label":"Open Targets: GUCY1A1 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000164116/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRA1A (via Phenylephrine Hydrochloride)","text":"Open Targets has no association between ADRA1A and cold-induced vasodilation.","source":{"label":"Open Targets: ADRA1A in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000120907/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRA1D (via Phenylephrine Hydrochloride)","text":"Open Targets has no association between ADRA1D and cold-induced vasodilation.","source":{"label":"Open Targets: ADRA1D in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000171873/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRA1B (via Phenylephrine Hydrochloride)","text":"Open Targets has no association between ADRA1B and cold-induced vasodilation.","source":{"label":"Open Targets: ADRA1B in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000170214/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRA2A (via Norepinephrine)","text":"Open Targets has no association between ADRA2A and cold-induced vasodilation.","source":{"label":"Open Targets: ADRA2A in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000150594/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRB1 (via Norepinephrine)","text":"Open Targets has no association between ADRB1 and cold-induced vasodilation.","source":{"label":"Open Targets: ADRB1 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000043591/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}},{"label":"ADRB2 (via Propranolol Hydrochloride)","text":"Open Targets has no association between ADRB2 and cold-induced vasodilation.","source":{"label":"Open Targets: ADRB2 in cold-induced vasodilation","url":"https://platform.opentargets.org/evidence/ENSG00000169252/EFO_0803534","date":"2026-11-11T22:45:33.812Z"}}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"no","detail":"Non-randomised","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"17 enrolled; each patient moves a rate by 100 ÷ 17 = 5.9 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Change in systolic, diastolic, and mean arterial blood pressure; Change in arterial blood flow; Change in vascular conductance (and 3 more)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"yes","detail":"Primary completion 2023-02-05, 45 months ago; no results posted","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},"context":[{"figure":"40.9% of applicable trials report results within a year","dataset":"Results-reporting studies summarised in spec §11","years":"all therapy areas","caveat":"All areas, not oncology only."}]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"161 terminated, withdrawn or suspended trials of drugs against GUCY1B1; 10 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"GUCY1B1: what already stopped","url":"/target/ENSG00000061918#stopped","date":"2026-11-11T22:45:33.880Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"yes","detail":"All 2 sites in Canada","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416?tab=locations","date":"2026-11-11T22:45:33.812Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMA/PE/0000182928 (propranolol hydrochloride, Treatment of arrhythmias): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 15 Apr 2025; EMEA-003091-PIP01-21 (acetylcysteine;paracetamol;phenylephrine, Treatment of upper respiratory tract infections): W: decision granting a waiver in all age groups for all conditions or indications, 31 Dec 2021; EMEA-001256-PIP02-12-M02 (phenylephrine hydrochloride;ketorolac trometamol (OMS302), Lens therapeutic procedures): W: decision granting a waiver in all age groups for all conditions or indications, 7 Dec 2018; EMEA-000511-PIP01-08-M04 (propranolol hydrochloride, Treatment of haemangioma): PM: decision on the application for modification of an agreed PIP, 21 Jan 2013; compliance positive 14 Feb 2013; +1 more","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/22/2713 positive 11 Nov 2022: Treatment of familial cerebral cavernous malformations; EU/3/19/2217 positive 17 Oct 2019: Treatment of retinopathy of prematurity; EU/3/17/1841 positive 27 Feb 2017: Treatment of von Hippel-Lindau disease; EU/3/16/1805 positive 12 Dec 2016: Treatment of soft tissue sarcoma; +1 more","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Hemangiol: authorised since 23 Apr 2014; Omidria: authorised since 28 Jul 2015","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"no","detail":"FDA's table lists no pediatric approval of Sodium Nitroprusside, Phenylephrine Hydrochloride, Norepinephrine, Propranolol Hydrochloride","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-11T22:45:33.899Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"198 interventional studies of Sodium Nitroprusside, Phenylephrine Hydrochloride, Norepinephrine, Propranolol Hydrochloride include patients under 18; 26 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Sodium+Nitroprusside%22+OR+%22Phenylephrine+Hydrochloride%22+OR+%22Norepinephrine%22+OR+%22Propranolol+Hydrochloride%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T22:45:33.907Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Cited case","text":"In February 2022 FDA asked its Oncologic Drugs Advisory Committee whether sintilimab's application, resting on ORIENT-11, a phase 3 run only in China, needed further trials showing it applies to US patients and US practice. One case, not a rule.","source":{"label":"FDA, ODAC 10 Feb 2022, draft questions","url":"https://www.fda.gov/media/156017/download","date":"2022-02-10"}},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"University of Alberta (academic or other)","source":{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"}},{"label":"principal investigator","text":"Sean van Diepen, MD, MSc, University of Alberta","source":{"label":"Person page","url":"/person/Sean%20van%20Diepen%2C%20MD%2C%20MSc","date":"2026-11-11T22:45:33.812Z"}},{"label":"principal investigator","text":"Craig D Steinback, PhD, University of Alberta","source":{"label":"Person page","url":"/person/Craig%20D%20Steinback%2C%20PhD","date":"2026-11-11T22:45:33.812Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT05525416","url":"https://clinicaltrials.gov/study/NCT05525416","date":"2026-11-11T22:45:33.812Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T22:45:33.812Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-11T22:45:33.809Z"}