{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05474846","title":"Combination Therapy for Treatment of Sleep Disturbance in Patients With Advanced Cancer","sponsor":"M.D. Anderson Cancer Center","phases":["PHASE2","PHASE3"],"status":"ACTIVE_NOT_RECRUITING","indication":null,"disease":"sleep"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of MTNR1A, MTNR1B, SLC6A3, SLC6A2 has somatic-mutation evidence in sleep","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: MTNR1A in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000168412/GO_0030431","date":"2026-11-11T20:07:52.887Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for MTNR1A, MTNR1B, SLC6A3, SLC6A2 in sleep","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: MTNR1A in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000168412/GO_0030431","date":"2026-11-11T20:07:52.887Z"},"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 NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},"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":"MTNR1A (via Melatonin)","text":"Open Targets has no association between MTNR1A and sleep.","source":{"label":"Open Targets: MTNR1A in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000168412/GO_0030431","date":"2026-11-11T20:07:52.887Z"}},{"label":"MTNR1B (via Melatonin)","text":"Open Targets has no association between MTNR1B and sleep.","source":{"label":"Open Targets: MTNR1B in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000134640/GO_0030431","date":"2026-11-11T20:07:52.887Z"}},{"label":"SLC6A3 (via Methylphenidate)","text":"Open Targets has no association between SLC6A3 and sleep.","source":{"label":"Open Targets: SLC6A3 in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000142319/GO_0030431","date":"2026-11-11T20:07:52.887Z"}},{"label":"SLC6A2 (via Methylphenidate)","text":"Open Targets has no association between SLC6A2 and sleep.","source":{"label":"Open Targets: SLC6A2 in sleep","url":"https://platform.opentargets.org/evidence/ENSG00000103546/GO_0030431","date":"2026-11-11T20:07:52.887Z"}}],"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 NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"169 enrolled; each patient moves a rate by 100 ÷ 169 = 0.6 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Pittsburgh Sleep Quality Index (PSQI) questionnaires","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},"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":"Primary completion expected 2027-02-28; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},"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":"84 terminated, withdrawn or suspended trials of drugs against MTNR1A; 9 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"MTNR1A: what already stopped","url":"/target/ENSG00000168412#stopped","date":"2026-11-11T20:07:52.906Z"}}],"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 NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846?tab=locations","date":"2026-11-11T20:07:52.887Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-003189-PIP01-22-M01 (Methylphenidate (hydrochloride), Treatment of Attention Deficit Hyperactivity Disorder (ADHD)): PM: decision on the application for modification of an agreed PIP, 24 Jan 2023; compliance positive 2 Feb 2023; EMEA-000440-PIP02-11-M05 (melatonin, Treatment of insomnia): PM: decision on the application for modification of an agreed PIP, 6 Apr 2017; compliance positive 21 Apr 2017; EMEA-002034-PIP01-16 (Methylphenidate (hydrochloride), Treatment of Attention Deficit Hyperactivity Disorder (ADHD)): W: decision granting a waiver in all age groups for all conditions or indications, 16 Mar 2017; EMEA-000440-PIP01-08 (melatonin, Primary insomnia): RW: decision refers to a refusal on a request for waiver in all age groups for the listed condition(s), 24 Mar 2009","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/3/12/978 positive 2 Apr 2012: Treatment of perinatal asphyxia; EU/3/23/2757 positive 15 Feb 2023: Treatment of perinatal asphyxia; - negative 28 Nov 2022: Treatment of retinopathy of prematurity; N/A negative 14 Oct 2022: Prevention of spaceflight-related radiation and microgravity; +15 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":"Tuzulby: authorised since 28 Feb 2025; Slenyto: authorised since 20 Sept 2018; Circadin: authorised since 29 Jun 2007; Melatonin Neurim: authorised since 7 Nov 2022","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 Melatonin, Methylphenidate","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":"2026-11-11T20:07:52.920Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"369 interventional studies of Melatonin, Methylphenidate include patients under 18; 56 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=%22Melatonin%22+OR+%22Methylphenidate%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T20:07:52.927Z"},"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":"M.D. Anderson Cancer Center (academic or other)","source":{"label":"ClinicalTrials.gov NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"}},{"label":"principal investigator","text":"Sriram Yennu, MD, MD Anderson","source":{"label":"Person page","url":"/person/Sriram%20Yennu%2C%20MD","date":"2026-11-11T20:07:52.887Z"}}],"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 NCT05474846","url":"https://clinicaltrials.gov/study/NCT05474846","date":"2026-11-11T20:07:52.887Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T20:07:52.887Z"},{"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":"2026-11-11T20:07:52.885Z"}