{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05388656","title":"Estrogen Variability and Irritability During the Menopause Transition","sponsor":"University of North Carolina, Chapel Hill","phases":["PHASE4"],"status":"COMPLETED","indication":null,"disease":"menopause"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of ESR1, MT-ND6, NDUFA10, NDUFS8, PGR has somatic-mutation evidence in menopause","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: ESR1 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000091831/GO_0042697","date":"2026-11-11T17:40:26.770Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for ESR1, MT-ND6, NDUFA10, NDUFS8, PGR in menopause","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: ESR1 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000091831/GO_0042697","date":"2026-11-11T17:40:26.770Z"},"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 NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"},"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":"ESR1 (via Estradiol Patch)","text":"Evidence types in menopause: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: ESR1 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000091831/GO_0042697","date":"2026-11-11T17:40:26.770Z"}},{"label":"MT-ND6 (via Extended Release)","text":"Open Targets has no association between MT-ND6 and menopause.","source":{"label":"Open Targets: MT-ND6 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000198695/GO_0042697","date":"2026-11-11T17:40:26.770Z"}},{"label":"NDUFA10 (via Extended Release)","text":"Open Targets has no association between NDUFA10 and menopause.","source":{"label":"Open Targets: NDUFA10 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000130414/GO_0042697","date":"2026-11-11T17:40:26.770Z"}},{"label":"NDUFS8 (via Extended Release)","text":"Open Targets has no association between NDUFS8 and menopause.","source":{"label":"Open Targets: NDUFS8 in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000110717/GO_0042697","date":"2026-11-11T17:40:26.770Z"}},{"label":"PGR (via Progesterone)","text":"Evidence types in menopause: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: PGR in menopause","url":"https://platform.opentargets.org/evidence/ENSG00000082175/GO_0042697","date":"2026-11-11T17:40:26.770Z"}}],"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":"yes","detail":"Randomised allocation","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"40 enrolled; each patient moves a rate by 100 ÷ 40 = 2.5 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Mean IDAS Ill Temper Scale Score Over Time","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"},"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":"no","detail":"Results posted 2025-11-26","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656?tab=results","date":"2026-11-11T17:40:26.770Z"},"context":[]}],"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":"235 terminated, withdrawn or suspended trials of drugs against ESR1; 23 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"ESR1: what already stopped","url":"/target/ENSG00000091831#stopped","date":"2026-11-11T17:40:26.798Z"}}],"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":"The only site is in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656?tab=locations","date":"2026-11-11T17:40:26.770Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-001109-PIP01-10 (progesterone, Treatment of female infertility): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 28 Sept 2011; EMEA-001137-PIP01-11 (progesterone, Treatment of female infertility;Prevention of recurrent spontaneous abortion): W: decision granting a waiver in all age groups for all conditions or indications, 10 Jun 2011","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/3/13/1101 withdrawn 8 Feb 2013: Treatment of moderate and severe traumatic brain injury; EU/3/05/275 positive 11 Apr 2005: Bronchopulmonary dysplasia in premature neonates of less than 30 weeks of gestational age","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":"no","detail":"EMA lists no centrally authorised medicine of Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release, Progesterone","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 Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release, Progesterone","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":"2026-11-11T17:40:26.817Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"347 interventional studies of Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release, Progesterone include patients under 18; 44 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=%22Estradiol+Patch%22+OR+%220.1+mg%2F24+Hours+Weekly+Transdermal+Film%22+OR+%22Extended+Release%22+OR+%22Progesterone%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T17:40:26.831Z"},"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":"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 North Carolina, Chapel Hill (academic or other)","source":{"label":"ClinicalTrials.gov NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"}},{"label":"principal investigator","text":"Susan Girdler, PhD, University of North Carolina, Chapel Hill","source":{"label":"Person page","url":"/person/Susan%20Girdler%2C%20PhD","date":"2026-11-11T17:40:26.770Z"}},{"label":"principal investigator","text":"Elizabeth Andersen, PhD, University of North Carolina, Chapel Hill","source":{"label":"Person page","url":"/person/Elizabeth%20Andersen%2C%20PhD","date":"2026-11-11T17:40:26.770Z"}}],"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 NCT05388656","url":"https://clinicaltrials.gov/study/NCT05388656","date":"2026-11-11T17:40:26.770Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T17:40:26.770Z"},{"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":"2026-11-11T17:40:26.765Z"}