Datasets:

anthonyyazdaniml

/

CT-ADE-SOC

like 1

NCT04692467

NCT04692467_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: PLWH 18-65 years of age ART duration ≥ 1 year, stable regimen ≥ 6 months HIV 1-RNA < 1,000 copies/mL within past 12 months Pre-HTN (SBP 120-139 or DBP 80-89 mm Hg) No current antihypertensive treatment Receives HIV care at GHESKIO Willing to provide consent Exclusion Criteria: Pregnancy Kidney disease or diabetes On protease inhibitor/ritonavir Advanced illness with limited life expectancy Plans to move out of the area within the next year Clinician determination that patient is unstable on ART

Participants randomized to the early HTN treatment arm will initiate 5mg daily of amlodipine immediately, increasing to 10 mg if SBP >130 mmHg after 1 month. Amlodipine 5mg: Amlodipine, Haiti's first-line antihypertensive medication, will be administered to the intervention group.

Amlodipine

CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1c1ccccc1Cl

C07FB07 | C07FB12 | C07FB13 | C08CA01 | C08CA17 | C08CA51 | C08GA02 | C09BB03 | C09BB04 | C09BB07 | C09BB13 | C09BX01 | C09BX03 | C09BX04 | C09DB01 | C09DB02 | C09DB04 | C09DB05 | C09DB06 | C09DB07 | C09DB09 | C09DX01 | C09DX03 | C09DX06 | C09DX07 | C09DX08 | C09XA53 | C09XA54 | C10BX03 | C10BX07 | C10BX09 | C10BX11 | C10BX14 | C10BX18 | C10BX19

NCT04697758

NCT04697758_EG000

No

All

Adult | Older Adult

Phase 1 | Phase 2

Inclusion Criteria: Patients 18 years of age or older with diabetic macular edema (DME) diagnosis secondary to diabetes mellitus Type 1 or 2 Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 65 to 23 in the study eye Willing and able to comply with clinic visits and study-related procedures Provide signed inform consent Exclusion Criteria: Any signs of high risk proliferative diabetic retinopathy in the study Previously-treated patients who are not responders to anti-VEGF Panretinal laser photocoagulation within 6 months and macular laser photocoagulation with 3 months of screening in the study eye Note: Other inclusion/exclusion criteria apply.

AXT107 0.1 mg/eye AXT107 0.1 mg: Single intravitreal injection of AXT107 0.1 mg/eye

Gersizangitide

CCC(C)C(NC(=O)C(CC(=O)O)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(C)NC(=O)C(Cc1ccccc1)NC(=O)C1CCCN1C(=O)C(C)NC(=O)C(NC(=O)C(CO)NC(=O)C(Cc1ccccc1)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(N)CC(C)C)C(C)O)C(C)CC)C(=O)NC(CC(N)=O)C(=O)NC(CC(=O)O)C(=O)NC(C(=O)NC(C(=O)NC(CC(N)=O)C(=O)NC(Cc1ccccc1)C(N)=O)C(C)CC)C(C)C

NCT04697758

NCT04697758_EG001

No

All

Adult | Older Adult

Phase 1 | Phase 2

Inclusion Criteria: Patients 18 years of age or older with diabetic macular edema (DME) diagnosis secondary to diabetes mellitus Type 1 or 2 Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 65 to 23 in the study eye Willing and able to comply with clinic visits and study-related procedures Provide signed inform consent Exclusion Criteria: Any signs of high risk proliferative diabetic retinopathy in the study Previously-treated patients who are not responders to anti-VEGF Panretinal laser photocoagulation within 6 months and macular laser photocoagulation with 3 months of screening in the study eye Note: Other inclusion/exclusion criteria apply.

AXT107 0.25 mg/eye AXT107 0.25 mg: Single intravitreal injection of AXT107 0.25 mg/eye

Gersizangitide

CCC(C)C(NC(=O)C(CC(=O)O)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(C)NC(=O)C(Cc1ccccc1)NC(=O)C1CCCN1C(=O)C(C)NC(=O)C(NC(=O)C(CO)NC(=O)C(Cc1ccccc1)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(N)CC(C)C)C(C)O)C(C)CC)C(=O)NC(CC(N)=O)C(=O)NC(CC(=O)O)C(=O)NC(C(=O)NC(C(=O)NC(CC(N)=O)C(=O)NC(Cc1ccccc1)C(N)=O)C(C)CC)C(C)C

NCT04697888

NCT04697888_EG000

No

All

Child

Phase 2 | Phase 3

Inclusion Criteria: The patient will be PN dependent and unable to meet nutritional needs solely by enteral nutrition. Patient will be <18 years of age. Direct bilirubin > 2.0mg/dl The patient must have failed standard therapies to prevent progression his/her liver disease. Exclusion Criteria: Other causes of chronic liver disease (Hepatitis C, Cystic fibrosis, biliary atresia, and alpha 1 anti-trypsin deficiency). Patients who are allergic to eggs/shellfish Patients who have severe hemorrhagic disorders.

Use of Omegaven for patients with parenteral nutrition associated liver disease. Omegaven: Expanded Access Therapy with Omegaven will be initiated at a starting dose of 0.5 gm/kg/day to be infused over 24 hrs. After two days of infusion the dose will be increased to 1gm/kg/day.

Promega

CCC=CCC=CCC=CCC=CCC=CCC=CCCC(=O)O.CCCC=CCC=CCC=CCC=CCC=CCCCC(=O)O

NCT04698525

NCT04698525_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Men and women from 18 to 65 years old. Diagnosis of migraine according to the ICHD-III of the IHS at least one year before the study. You must have at least 4-14 migraine attacks per month. Not receiving prophylactic treatment for migraine Sign informed consent Exclusion Criteria: Pregnant or lactating patients. Patients with another type of non-migraine headache. Allergy to Sodium Valproate and/or Memantine Being a carrier of systemic disease (infectious, immunological, or metabolic processes) or cardiovascular (myocardial, coronary, or valvular disease) prevents their participation in the study.

VPA is a well know antiepileptic drug with multiple side effects. However, in low doses are a few side effects problems.

Valproate Sodium

CCCC(CCC)C(=O)[O-].[Na+]

NCT04698525

NCT04698525_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Men and women from 18 to 65 years old. Diagnosis of migraine according to the ICHD-III of the IHS at least one year before the study. You must have at least 4-14 migraine attacks per month. Not receiving prophylactic treatment for migraine Sign informed consent Exclusion Criteria: Pregnant or lactating patients. Patients with another type of non-migraine headache. Allergy to Sodium Valproate and/or Memantine Being a carrier of systemic disease (infectious, immunological, or metabolic processes) or cardiovascular (myocardial, coronary, or valvular disease) prevents their participation in the study.

Memantine is a tolerable drug. However, it is always necessary to ask for side effects in this type o research.

Memantine

CC12CC3CC(C)(C1)CC(N)(C3)C2

N06DA52 | N06DA53 | N06DX01

NCT04699461

NCT04699461_EG001

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Written informed consent must be obtained prior to any study procedures. Male or female participants aged 18 years or older, with pathologic diagnosis of follicular lymphoma (FL) (Grade 1, 2, 3A) in the most recent tumor biopsy. Relapsed or refractory disease following two or more treatment regimens, at least one of which must have contained an anti-CD20 therapy. Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy. Measurable disease as defined by the 2014 Lugano Classification as assessed by positron emission tomography - computed tomography (PET-CT) or, if not Fluorodeoxyglucose (FDG) avid, CT or magnetic resonance imaging (MRI). Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available). Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. Adequate organ function as defined by screening laboratory values within the following parameters: Absolute neutrophil count (ANC) ≥1.0 × 10^3/μL (off growth factors at least 72 hours), Platelet count ≥75 × 10^3/μL without transfusion in the past 2 weeks, Alanine aminotransferase, AST, and GGT ≤2.5 × the upper limit of normal (ULN), Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN), Calculated creatinine clearance ≥30 mL/min by the Cockcroft and Gault equation. Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility Women of childbearing potential (WOCBP)(1) must agree to use a highly effective method(2) of contraception from the time of giving informed consent until at least 9 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 6 months after the participant receives his last dose of study treatment. WOCBP are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include hormonal contraceptives associated with inhibition of ovulation (oral, injectable, patch, intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the participant. Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception. Exclusion Criteria: Previous treatment with loncastuximab tesirine. Previous treatment with idelalisib. History of hypersensitivity to any of the excipients of loncastuximab tesirine or idelalisib. Follicular lymphoma which has transformed to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas. Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor, inducer, or sensitive substrate. History of or ongoing drug-induced pneumonitis. History of or ongoing inflammatory bowel disease. Any condition that could interfere with the absorption or metabolism of idelalisib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. Autologous transplant within 30 days prior to start of study treatment (C1D1). Allogenic transplant within 60 days prior to start of study treatment (C1D1). Active graft-versus-host disease. Post-transplantation lymphoproliferative disorders. Human immunodeficiency virus (HIV) seropositive with any of the following: CD4+ T-cell counts <350 cells/μL. Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening. Not on anti-retroviral therapy, or on anti-retroviral therapy for < 4 weeks at the time of screening. HIV viral load ≥400 copies/mL. Serologic evidence of chronic hepatitis B infection and unable or unwilling to receive standard prophylactic anti-viral therapy or with detectable hepatitis B virus (HBV) viral load. Serologic evidence of hepatitis C infection without completion of curative treatment or with detectable hepatitis C virus (HCV) viral load. History of Stevens-Johnson syndrome or toxic epidermal necrolysis. Lymphoma with active central nervous system involvement, including leptomeningeal disease. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath). Breastfeeding or pregnant. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (BP ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. Any Grade ≥3 active infection which requires IV antibiotics, IV antiviral, or IV antifungal treatment. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study treatment (C1D1), except shorter if approved by the Sponsor. Use of any other experimental medication within 30 days prior to start of study treatment (C1D1). Live vaccine administration within 4 weeks prior to Cycle(C) 1 Day (D) 1. Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (except ≤Grade 2 neuropathy or alopecia) due to previous therapy prior to screening. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.

Participants were administered 150 mg idelalisib, orally, twice a day throughout each cycle, where 1 cycle is 4 weeks. 1 participant received 6 cycles and the other participant received 13 cycles of treatment. The treatment duration was 140 days and 333 days, respectively.

Idelalisib

[H][C@@](CC)(Nc1ncnc2[nH]cnc12)c1nc2cccc(F)c2c(=O)n1-c1ccccc1

L01EM01

NCT04700280

NCT04700280_EG000

No

All

Adult | Older Adult

Phase 2

Key Inclusion Criteria: Documented diagnosis of pSS for <10 years prior to screening AND defined by the classification criteria >=4 described by the American College of Rheumatology - European League Against Rheumatism (ACR-EULAR). Participant has an ESSDAI score >=5 assessed on 7 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, hematological, and biological. Participant has an ESSPRI score >=5. Participant has stimulated whole salivary flow rate of >=0.1 milliliter per minute (mL/min). Participant has positive serum titers of anti-Sjögren's-syndrome-related antigen A (anti-SS-A)/Ro and/or anti-SS-B/La antibodies. Participants already on treatment should be on stable standard of care (SoC) for at least 4 weeks prior to first investigational product (IP) dosing. The following SoC medications are permitted: Corticosteroids <=7.5 mg/day (prednisone or equivalent); AND/OR Non-steroidal anti-inflammatory drugs (NSAIDs); AND/OR One single antimalarial at a stable dose (hydroxychloroquine <=400 mg/day; quinacrine 100 mg/kg/day, or chloroquine <=250 mg/day); AND/OR One single immunosuppressant at a stable dose (methotrexate [MTX] <=10 mg/week or azathioprine [AZA] <=2 mg/kg/day); AND/OR One single cholinergic stimulant at a stable dose (e.g., pilocarpine, cevimeline). Female participant of childbearing potential must have a negative highly sensitive (serum beta human chorionic gonadotropin or urine dipstick) pregnancy test. Female participant of childbearing potential or male participant must agree to use highly effective contraception/preventive exposure measures. Key Exclusion Criteria: Secondary Sjögren's syndrome according to the ACR-EULAR (2016) classification. History or presence of unstable condition not related to Sjögren's Syndrome that, in the opinion of the investigator, could constitute an unacceptable risk when taking the IP or interfere with the interpretation of data. Participant has any active systemic infection within 2 weeks prior to first IP dosing, or poorly controlled chronic cardiac, pulmonary, or renal disease. Participant has a known or suspected history of or a current immunosuppressive condition, or a history of opportunistic infections (e.g., human immunodeficiency virus [HIV] infection, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis). Participant has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV surface antigen (HBsAg) positivity. Participant has hepatitis C virus (HCV) infection, as defined by positive HCV antibody at screening and detectable HCV viremia. Participants with positive HCV antibody must undergo reflex HCV ribonucleic acid (RNA) testing, and participants with HCV RNA positivity will be excluded. Participants with positive HCV antibody and negative HCV RNA are eligible. Participant testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as detected at screening based on real time polymerase chain reaction (RT-PCR) or at baseline based on immunoglobulin M (IgM) immunoassay, or participants who have been in contact with SARS-CoV-2 infected individuals in the 2 weeks prior to first dosing of IP. Participants presenting any signs or symptoms of SARS-CoV-2 infection, as detected prior to first IP dosing following careful physical examination (e.g., cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc). In addition, any other locally applicable standard diagnostic criteria may also apply to rule out SARS-CoV-2 infection. Participant has taken any disallowed therapies: Mycophenolate mofetil (MMF) within a week prior to screening. Cyclosporine/Tacrolimus within a week prior to screening. Cyclophosphamide within 6 months prior to screening. Ocular medicines (e.g., topical cyclosporine, topical NSAIDs/ corticosteroids) for at least 4 weeks prior to screening, except for a sporadic use. Biologics such as, but not limited to, rituximab, abatacept, and any other unapproved biologic within 6 months prior to screening. Plasmapheresis within 12 weeks prior to screening. Plasma exchange within 12 weeks prior to screening. Intravenous immunoglobulin (IVIG) therapy within 24 weeks prior to screening. Other prohibited medications within 2 weeks or 5 half-lives, whichever is longer, prior to first IP dosing. Concurrent use of anticholinergic agents or any other medication known to cause dry mouth/dry eyes that, in the opinion of the investigator, are a contributing factor to the participant's dryness and/or use of anticholinergic agents not contributing to this dryness, if not stable at least 4 weeks prior to screening. Participant has a history of tuberculosis (TB) diagnosis or evidence of active or latent infection with Mycobacterium tuberculosis. Participant has a history of lymphoma or any malignancy within the past 5 years prior to screening with the exception of excised and curatively treated non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of cervix which is considered cured with minimal risk of recurrence. Participant has severe organ manifestation or life-threatening condition, or has planned a surgery during the study. Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Participants received GLPG3970 400 mg (2 *200 mg tablet), orally, once daily for 12 weeks.

UA6B2TI4MO

COc1cc(-c2cnc3cc(OCCN4CCOCC4)ccn23)cc2c1C(=O)N(CC(F)(F)F)CC2

NCT04701593

NCT04701593_EG001

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: Patient must have rhegmatogenous retinal detachment and be scheduled to undergo scleral buckle surgery for correction Exclusion Criteria: Advanced Glaucoma History of corticosteroid responsive elevation in IOP Allergy to Triamcinolone Acetonide or other corticosteroids Pre-existing chronic pain disorders Herpes zoster Prior corneal allograft Allergy to local anesthetic or penicillin Patients unable to consent on own behalf Patients unable to communicate pain and nausea levels Pregnancy Incarceration

receives a sub-tenon irrigation of 1 cc 40mg/mL triamcinolone acetonide around the base of the scleral buckle (0.25 cc in each quadrant) at time of operation Triamcinolone Acetonide 40mg/mL: Sub-tenon irrigation 1cc

Kenalog

CC1(C)OC2CC3C4CCC5=CC(=O)C=CC5(C)C4(F)C(O)CC3(C)C2(C(=O)CO)O1

NCT04704713

NCT04704713_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Aged greater than 18 years Male or female patients with a documented history of PLE diagnosed or confirmed by a photodermatologist or photobiologist, with a history of PLE related pruritus symptoms. Recurrent PLE episodes that occur at least once a year (as evidenced by PLE related pruritus symptoms) developing in their own country (to exclude patients affected only when traveling to sunnier climates) Written informed consent prior to the performance of any study-specific procedure Are willing and able to comply with the conditions specified in the protocol and study procedures in the opinion of the Investigator Exclusion Criteria: Currently requiring treatment with systemic immunosuppressive agents Documented history of other photosensitivity conditions which may be confused with PLE or interfere with the assessment of PLE episodes Solarium use in the three months prior to study involvement and throughout the duration of the study Use of immunosuppressive medications, drugs that cause hyperpigmentation or any other treatment that in the opinion of the Investigator may interfere with this study Documented presence (> 1 in 320) of Anti-Nuclear Antibody (ANA) and/or positive Extractable Nuclear Antibody (ENA); historical results from the 3 years prior to randomisation are acceptable if available In the opinion of the Investigator, any evidence of clinically significant organ dysfunction, or any clinically significant deviation from normal in clinical or laboratory parameters History of drug or alcohol abuse (in the last 1 year) Female who is pregnant (confirmed by positive serum beta-Human chorionic gonadotropin (β-HCG) pregnancy test prior to baseline) or lactating Female of child-bearing potential (pre-menopausal, not surgically sterile) that is not using or is not willing to use adequate contraceptive measures (e.g. oral contraceptives, condoms, diaphragm plus spermicide, intrauterine device) Sexually active men with partners of child bearing potential not willing to use barrier contraception during the trial and for a period of three months thereafter Participation in a clinical trial with another Investigational Medicinal Product (IMP) within 30 days prior to the Screening visit or during the study Hypersensitivity to afamelanotide or any of its components

Afamelanotide implants were administered on Days 0 and 60. Patients returned to the clinic on Day 120 for the final visit. Afamelanotide

Afamelanotide

CCCCC(NC(=O)C(CO)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(C)=O)C(=O)NC(CCC(=O)O)C(=O)NC(Cc1cnc[nH]1)C(=O)NC(Cc1ccccc1)C(=O)NC(CCCNC(=N)N)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NCC(=O)NC(CCCCN)C(=O)N1CCCC1C(=O)NC(C(N)=O)C(C)C

D02BB02

NCT04706091

NCT04706091_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: Men or women of any ethnic origin Written informed consent is obtained Speaks and writes in English A willingness and ability to comply with study procedures Age 25-85 years Diagnosis of RLS via Cambridge-Hopkins RLS questionnaire International Restless Legs Syndrome Study Group scale score (IRLS) < 15 RLS treatment with a dopaminergic agonist or an alpha-2-delta agent No changes in RLS medication in the previous month DSM-5 criteria for Insomnia Disorder Report a total sleep time ≤ 7 hours and wake after sleep onset (WASO) > 45 minutes on 7 or more of the 14 nightly sleep logs during both the initial 2-week screening period and the two-week screening run-in period. WASO does not decrease by more than 50% on the 2-week sleep diary obtained between the screening visit and the randomization visit Exclusion Criteria: Diagnosis of moderate/severe obstructive sleep apnea (AHI > 30) not using continuous positive airway pressure therapy (CPAP) (can be included if CPAP adherent), or other untreated primary sleep disorders (e.g. narcolepsy) Shift workers Unwillingness to not use sedative-hypnotics (other than suvorexant) during the study period Unwillingness to maintain stable RLS medication during the study unless medically indicated Current use of an opiate medication Unwillingness to not take stimulants (e.g. caffeine) after 4:00 pm during the study Current major depressive episode, by report and as indicated by the Patient Health Questionnaire (PHQ-9) Lifetime history of bipolar disorder, psychosis, or other serious psychiatric illness Current alcohol/substance use disorder BMI ≥ 40 kg/m^2 Renal or hepatic disease judged to interfere with drug metabolism and excretion Pregnancy or breastfeeding Malignancy within past 2 years Surgery within past 3 months Neurological disorder or cardiovascular disease raising safety concerns about use of suvorexant and/or judged to interfere with ability to assess efficacy of the treatment Medical instability considered to interfere with study procedures Concomitant medications with drug interaction or co-administration concerns Contraindications or allergic responses to suvorexant History of being treated with suvorexant Travel across two time-zones during the week prior to enrollment Greater than 6 cups of coffee per day

Participants in both arms of the study received suvorexant treatment, either during treatment one or treatment two.

Suvorexant

[H][C@@]1(C)CCN(c2nc3cc(Cl)ccc3o2)CCN1C(=O)c1cc(C)ccc1-n1nccn1

N05CJ01 | N05CM19

NCT04707469

NCT04707469_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive). BMI equal to or above 25 kg/m^2 Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens: No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *: Metformin (equal to or above1500 mg or maximum tolerated or effective dose). Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose). Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose). Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label). Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out). Exclusion Criteria: Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed. Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 68.

Semaglutide

CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C

A10BJ06

NCT04707469

NCT04707469_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive). BMI equal to or above 25 kg/m^2 Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens: No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *: Metformin (equal to or above1500 mg or maximum tolerated or effective dose). Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose). Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose). Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label). Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out). Exclusion Criteria: Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed. Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to 12 and 25 mg from week 12 to week 68.

Semaglutide

CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C

A10BJ06

NCT04707469

NCT04707469_EG002

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive). BMI equal to or above 25 kg/m^2 Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens: No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *: Metformin (equal to or above1500 mg or maximum tolerated or effective dose). Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose). Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose). Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label). Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out). Exclusion Criteria: Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed. Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to 12, 25 mg from week 12 to week 16 and 50 mg from week 16 to week 68.

Semaglutide

CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C

A10BJ06

NCT04707534

NCT04707534_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: Age ≥ 18 years old RT-PCR confirmed COVID-19 infection Positive pressure ventilation (non-invasive or invasive) or high flow nasal cannula (HFNC) or need supplemental oxygen with oxygen mask or nasal cannula Exclusion Criteria: Underlying disease requiring chronic corticosteroids Severe adverse events before admission, i.e. cardiac arrest; Contraindication for corticosteroids; Death is deemed to be imminent and inevitable during the next 24 hours Recruited in other clinical intervention trial Pregnancy Patient on judicial protection

Dexamethasone 20 mg daily for 5 days, followed by dexamethasone 10 mg daily for 5 days Dexamethasone: Dexamethasone

Betamethasone

CC1CC2C3CCC4=CC(=O)C=CC4(C)C3(F)C(O)CC2(C)C1(O)C(=O)CO

A01AC02 | A07EA04 | C05AA05 | C05AA09 | D07AB19 | D07AC01 | D07BC01 | D07CB04 | D07CC01 | D07XB05 | D07XC01 | D10AA03 | H02AB01 | H02AB02 | R01AD03 | R01AD06 | R01AD53 | R03BA04 | S01BA01 | S01BA06 | S01BB04 | S01CA01 | S01CA05 | S01CB01 | S01CB04 | S02BA06 | S02BA07 | S02CA06 | S03BA01 | S03BA03 | S03CA01 | S03CA06

NCT04707534

NCT04707534_EG001

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: Age ≥ 18 years old RT-PCR confirmed COVID-19 infection Positive pressure ventilation (non-invasive or invasive) or high flow nasal cannula (HFNC) or need supplemental oxygen with oxygen mask or nasal cannula Exclusion Criteria: Underlying disease requiring chronic corticosteroids Severe adverse events before admission, i.e. cardiac arrest; Contraindication for corticosteroids; Death is deemed to be imminent and inevitable during the next 24 hours Recruited in other clinical intervention trial Pregnancy Patient on judicial protection

Dexamethasone 6 mg daily for 10 days Dexamethasone: Dexamethasone

Betamethasone

CC1CC2C3CCC4=CC(=O)C=CC4(C)C3(F)C(O)CC2(C)C1(O)C(=O)CO

A01AC02 | A07EA04 | C05AA05 | C05AA09 | D07AB19 | D07AC01 | D07BC01 | D07CB04 | D07CC01 | D07XB05 | D07XC01 | D10AA03 | H02AB01 | H02AB02 | R01AD03 | R01AD06 | R01AD53 | R03BA04 | S01BA01 | S01BA06 | S01BB04 | S01CA01 | S01CA05 | S01CB01 | S01CB04 | S02BA06 | S02BA07 | S02CA06 | S03BA01 | S03BA03 | S03CA01 | S03CA06

NCT04707664

NCT04707664_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Patients with a positive laboratory diagnosis of SARS-CoV-2 infection by an antigen or a molecular test ≤5 days prior to randomization. The test should have been authorized by the relevant regulatory authority. Have one or more of the following mild or moderate COVID-19 symptoms for ≤5 days prior to randomization: Fever or chills New onset or worsening cough Sore throat Malaise or fatigue Headache Muscle pain (myalgias) or body aches Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) New onset or worsening shortness of breath or difficulty breathing Nasal congestion or runny nose New loss of taste (ageusia) and/or smell (anosmia). Note: any of these symptoms (ageusia, anosmia) alone or in combination cannot be used as the SOLE qualifying symptoms for enrollment. At higher risk for progression to more severe COVID-19 Age ≥ 60 years Age 18-59 years with a clinically stable medical history of at least 1 or more of the following conditions that could lead to severe COVID-19: Chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis Obesity with BMI ≥ 30 kg/m2 Cardiovascular disease Sickle cell disease or thalassemia Diabetes mellitus being managed with concomitant medications Hypertension being managed with concomitant medications Chronic kidney disease Oxygen saturation by pulse oximeter > 93% on room air. Note: at altitudes of >4000 feet above sea level, oxygen saturation by pulse oximeter > 91% on room air is permitted Negative pregnancy test (if woman of childbearing potential) Females of childbearing potential and males with female partners of childbearing potential must agree to use acceptable contraceptive methods from screening to Day 28 The patient (or legally authorized decision maker) must give informed consent Exclusion Criteria: Hospitalized patients Patients who have received or are receiving other treatments that are not approved/authorized by the relevant regulatory authority for the treatment of patients with mild or moderate COVID-19 in an outpatient setting Patients enrolled in interventional clinical trials for other experimental therapies Patients on chronic oxygen supplementation due to cardiopulmonary or other conditions Patients with unstable comorbid conditions (e.g., decompensated congestive heart failure, COPD with exacerbation, current angina pectoris, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled asthma) Patients with severe pulmonary comorbid conditions, including systemic steroid-dependent asthma, systemic steroid-dependent COPD, oxygen-dependent COPD, lung transplant, or cystic fibrosis Patients who have received highly immunosuppressive therapy (to include systemic corticosteroids) or anti-cancer combination chemotherapy within 24 hours prior to first dose of study drug Patients with known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product Patients who have previously experienced severe and unexplained side effects during aerosol delivery of any kind of medical product Pregnant or breastfeeding females Patients who, in the opinion of the Investigator, will not be able to comply with all the study procedures and visits as outlined in the schedule of events, including follow-up

Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: All patients randomized to the sargramostim treatment arm will be treated with 250 mcg inhaled sargramostim administered via a vibrating mesh nebulizer once daily for 5 days.

Zidovudine

Cc1cn([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)c(=O)[nH]c1=O

J05AF01 | J05AR01 | J05AR04 | J05AR05

NCT04709835

NCT04709835_EG001

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test)at screening Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days prior to randomization Exclusion Criteria: Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate ≥30, heart rate ≥125, peripheral capillary oxygen saturation ≤93% on room air Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct acting antivirals, convalescent plasma, monoclonal antibodies against SARS CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to screening Requirement, in the opinion of the investigator, for any of the prohibited medications during the study Use of hydroxychloroquine or amiodarone within 3 months of screening Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-527. Women of childbearing potential must have a negative urine pregnancy test result at screening Abnormal laboratory test results at screening Clinically significant abnormal ECG, as determined by the Investigator, at screening Planned procedure or surgery during the study Known allergy or hypersensitivity to study drug or drug product excipients Substance abuse, as determined by the investigator, within 12 months prior to screening Poor peripheral venous access Malabsorption syndrome or other condition that would interfere with enteral absorption Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion History of anaphylaxis Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.

Bemnifosbuvir hemisulfate

CNc1nc(N)nc2c1ncn2C1OC(COP(=O)(NC(C)C(=O)OC(C)C)Oc2ccccc2)C(O)C1(C)F.CNc1nc(N)nc2c1ncn2C1OC(COP(=O)(NC(C)C(=O)OC(C)C)Oc2ccccc2)C(O)C1(C)F.O=S(=O)(O)O

NCT04709835

NCT04709835_EG002

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test)at screening Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days prior to randomization Exclusion Criteria: Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate ≥30, heart rate ≥125, peripheral capillary oxygen saturation ≤93% on room air Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct acting antivirals, convalescent plasma, monoclonal antibodies against SARS CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to screening Requirement, in the opinion of the investigator, for any of the prohibited medications during the study Use of hydroxychloroquine or amiodarone within 3 months of screening Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-527. Women of childbearing potential must have a negative urine pregnancy test result at screening Abnormal laboratory test results at screening Clinically significant abnormal ECG, as determined by the Investigator, at screening Planned procedure or surgery during the study Known allergy or hypersensitivity to study drug or drug product excipients Substance abuse, as determined by the investigator, within 12 months prior to screening Poor peripheral venous access Malabsorption syndrome or other condition that would interfere with enteral absorption Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion History of anaphylaxis Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.

Bemnifosbuvir hemisulfate

CNc1nc(N)nc2c1ncn2C1OC(COP(=O)(NC(C)C(=O)OC(C)C)Oc2ccccc2)C(O)C1(C)F.CNc1nc(N)nc2c1ncn2C1OC(COP(=O)(NC(C)C(=O)OC(C)C)Oc2ccccc2)C(O)C1(C)F.O=S(=O)(O)O

NCT04711837

NCT04711837_EG000

Accepts Healthy Volunteers

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Subjects undergoing elective surgery (nonemergency, noncardiothoracic, and nonintracranial surgery anticipated to last at least 1 hour ). Males or females, aged ≥18 years old, with American Society of Anesthesiologists Physical Status (ASA PS) I to IV. Body mass index (BMI) ≥18 kg/m2. For all females of childbearing potential, negative pregnancy test at screening and baseline. Additionally, females of childbearing potential must agree to use birth control (such as condom, intrauterine device [IUD], abstinence) from the time of consent until 30 days post study drug administration. Capable of understanding the procedures and methods of this study, willing to sign an Informed Consent Form, and to complete this study in strict compliance with the study protocol. Exclusion Criteria: Contraindications to deep sedation/general anesthesia or a history of adverse reaction to sedation/general anesthesia. Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol; subject having contraindications to propofol, opioids, and their antidotes. Medical condition or evidence of increased sedation/general anesthesia risk. Management risks of respiratory tract and judged by the investigator to be unsuitable for inclusion in the study. Any medication that has the potential to interact synergistically with propofol or HSK3486, including but not limited to all sedatives and hypnotics. Laboratory parameters significantly out of range at screening. Female subjects with a positive pregnancy test (serum or urine) at screening or baseline; lactating subjects; any subject planning to get pregnant within 1 month after the study (including the male subject's partner). Judged by the investigator to have any other factors that make the subject unsuitable for participation in the study.

HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.

Cipepofol

CC(C)c1cccc(C(C)C2CC2)c1O

NCT04711837

NCT04711837_EG001

Accepts Healthy Volunteers

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Subjects undergoing elective surgery (nonemergency, noncardiothoracic, and nonintracranial surgery anticipated to last at least 1 hour ). Males or females, aged ≥18 years old, with American Society of Anesthesiologists Physical Status (ASA PS) I to IV. Body mass index (BMI) ≥18 kg/m2. For all females of childbearing potential, negative pregnancy test at screening and baseline. Additionally, females of childbearing potential must agree to use birth control (such as condom, intrauterine device [IUD], abstinence) from the time of consent until 30 days post study drug administration. Capable of understanding the procedures and methods of this study, willing to sign an Informed Consent Form, and to complete this study in strict compliance with the study protocol. Exclusion Criteria: Contraindications to deep sedation/general anesthesia or a history of adverse reaction to sedation/general anesthesia. Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol; subject having contraindications to propofol, opioids, and their antidotes. Medical condition or evidence of increased sedation/general anesthesia risk. Management risks of respiratory tract and judged by the investigator to be unsuitable for inclusion in the study. Any medication that has the potential to interact synergistically with propofol or HSK3486, including but not limited to all sedatives and hypnotics. Laboratory parameters significantly out of range at screening. Female subjects with a positive pregnancy test (serum or urine) at screening or baseline; lactating subjects; any subject planning to get pregnant within 1 month after the study (including the male subject's partner). Judged by the investigator to have any other factors that make the subject unsuitable for participation in the study.

Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.

Propofol

CC(C)c1cccc(C(C)C)c1O

N01AX10

NCT04715932

NCT04715932_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Covid-19 positive by polymerase chain reaction (PCR) testing; Participant must be able to evaluate their symptoms and report them in the symptoms diary; Patients must be able to take their oral temperature daily with an electronic thermometer provided to them with study materials; Males and females, at least 18 years of age, capable and willing to provide informed consent; Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing at least one method of contraception and preferably two complementary forms of contraception including a barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, diaphragm, intrauterine device (IUD)) throughout the study; Patient must have received a diagnosis of COVID-19 infection within the last 48 hours and have one or more symptoms; Outpatient setting (not currently hospitalized or under immediate consideration for hospitalization); Patient must be able and willing to comply with the requirements of this study protocol. Exclusion Criteria: Patient currently hospitalized or under immediate consideration for hospitalization; Patient currently in shock or with hemodynamic instability; Patient undergoing chemotherapy for cancer; Patient is unable to take oral temperature using an electronic thermometer; Patient who received at least one dose of the COVID-19 vaccine; Female patient who is pregnant or breast-feeding or is considering becoming pregnant during the study; People taking anticoagulant/antiplatelet medications, those with bleeding disorders, and people two weeks before or after surgery; Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study; Regular consumption of natural products containing more than 150 mg of hesperidin or regular consumption of more than 1 glass of orange juice per day; Known allergy to any of the medicinal and non-medicinal ingredient: hesperidin, microcrystalline cellulose, magnesium stearate.

Patients will receive study medication Hesperidin and will take 2 capsules of 500mg at the same time in the evening, at bedtime with water.

Hesperidin

COc1ccc([C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2)cc1O

NCT04716413

NCT04716413_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: Age range 18-100 years Currently taking Suboxone ASA (American Society of Anesthesiology) physical score 1-3 Able to provide a signed informed consent General anesthesia (either endotracheal intubation or laryngeal mask airway) or MAC (monitored anesthesia care) without the use of regional anesthesia Exclusion Criteria: Known allergic reactions to Dsuvia and its excipients Severe respiratory illness including exacerbation of asthma attack Significant intraoperative hemodynamic instability Use of Regional anesthesia techniques

Subjects will receive dose of Dsuvia 30mcg SL (1st dose) after induction but before first incision. Post-operatively, if subject rates pain higher than 4 out of 10, subject will receive a second dose of Dsuvia 30mcg SL (sublingual). If 30 minutes after second dose, subject rates pain higher than 4 out of 10, subject will receive ibuprofen 800mg IV. If 60 minutes after second dose, subject rates pain higher than 7 out of 10, subject will receive hydromorphone 0.4 mg IV. Dsuvia: Subject will receive up to 2 doses of Dsuvia. The first dose will be intra-op and the second dose will be post-op (if needed)

Sufentanil

CCC(=O)N(c1ccccc1)C1(COC)CCN(CCc2cccs2)CC1

N01AH03

NCT04716426

NCT04716426_EG000

Accepts Healthy Volunteers

All

Adult | Older Adult

Not Applicable

Inclusion Criteria: good general health (without serious health problems); tested negative, by means of immunoglobulin (Ig) G and IgM serology tests and chain real-time polymerase chain reaction (RT-PCR), for COVID-19. Exclusion Criteria: previous immunization against COVID-19; allergy to tetracycline hydrochloride; diagnosis of Lyme disease; immunocompromised; share housing with someone diagnosed with COVID-19 at the time of the baseline evaluation; serious illnesses, such as cancer, kidney failure, decompensated cardiorespiratory and metabolic diseases, etc.

4 drops of tetracycline hydrochloride 3% (APT™ T3X) applied inside of the nasal channels and inside of nostrils, once a day, every day for 21 days (except health professionals that will be instructed to use 4 drops of APT™ T3X twice a day, every day for 21 days. Tetracycline hydrochloride 3%: Proprietary formulation composed of FDA approved inactive ingredients and the active pharmaceutical ingredient tetracycline hydrochloride.

Tetracycline hydrochloride

CN(C)C1C(=O)C(C(N)=O)=C(O)C2(O)C(=O)C3=C(O)c4c(O)cccc4C(C)(O)C3CC12.Cl

NCT04720105

NCT04720105_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria Subject is able to provide written, informed consent and comply with the study protocol. Subject is at least 18 years of age. Subject has a diagnosis of plaque-type palmar and/or plantar psoriasis. Patient has at least one psoriatic plaque outside of the palms and soles or psoriatic nail findings. Subject has a ppPGA ≥ 3 at screening/baseline visit. Subject is using adequate birth control during the study period as defined as follows: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. OR Option 3: Abstinence from sex when it is a lifestyle choice, and not just a social circumstance. Exclusion Criteria Subject is not able to provide written, informed consent and comply with the study protocol. Subject is less than 18 years of age. Subject has non-plaque type psoriasis on the hands and/or feet. Patient does not have any evidence of psoriasis elsewhere. Subject has concurrent cutaneous disease affecting the hands and/or feet that would interfere with assessments. Subject has a ppPGA < 3 at screening/baseline visit. Subject refuses to discontinue concomitant prescription medications on hands and/or feet. Subject has used topical prescription treatments or received phototherapy treatment for psoriasis within 2 weeks of screening/baseline visit. Subject has used intralesional kenalog within 4 weeks of screening/baseline visit. Subject has taken oral treatments for psoriasis within 4 weeks of screening/baseline visit. Subject has received any treatment with biologic medications within 5 half-lives (if known) or 16 weeks prior to screening/baseline, whichever is longer. Subject refuses to use adequate birth control during the duration of the study period. Subject is currently pregnant or breastfeeding.

Participants with plaque type psoriasis to be treated with Duobrii® (halobetasol propionate 0.01%/tazarotene 0.045% lotion, HP/TAZ) to be applied thinly once a day on the affected areas of hands and/or feet at weeks 0,2,8,16 for a total of 24 weeks.

Tazarotene

CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(C)(C)CCS3)nc1

D05AX05 | D05AX55

NCT04726969

NCT04726969_EG001

No

All

Child | Adult

Phase 3

Inclusion Criteria: Aged between 12 and 60 years Written informed consent signed by either parents/caregivers for underage adolescents (aged 12-17 years) or by the participant him/herself (18-60 years of age); and written assent by underage participant Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and at follow-up assessment 14-21 days after treatment Willing to be examined by a study physician prior to treatment At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura and infection intensities of at least 48 EPG Exclusion Criteria: Presence or signs of major systemic illnesses, e.g. body temperature ≥ 38°C, severe anemia (below 80g/l Hb according to WHO) upon initial clinical assessment Known or suspected infection with Loa loa History of acute or severe chronic disease Abnormal liver function assessed by multiple biochemical blood-based analyses Recent use of anthelmintic drug (within past 4 weeks) Attending other clinical trials during the study Pregnancy, lactating, and/or planning to become pregnant within the next 3 months Known allergy to study medications (i.e. albendazole, ivermectin or moxidectin) Taking medication with known contraindication to or interaction with study drugs

Placebo (for moxidectin, 4 tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0 Albendazole 400 mg Oral Tablet: Tablets of 400 mg albendazole

Albendazole

CCCSc1ccc2nc(NC(=O)OC)[nH]c2c1

P02CA03

NCT04728802

NCT04728802_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Admitted to the hospital with symptoms of COVID-19 Male and females age ≥18 years old Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 3, 4, 5, or 6 Coagulation: INR ≤ 1.5×ULN, and APTT ≤ 1.5×ULN Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study Exclusion Criteria: Subject enrolled in a study to investigate a treatment for COVID-19 Requires mechanical ventilation Subject taking an anti-androgen of any type including: androgen depravation therapy, 5-alpha reductase inhibitors, etc… Patients who are allergic to the investigational product or similar drugs (or any excipients); Subjects who have malignant tumors in the past 5 years, with the exception of completed resected basal cell and squamous cell skin cancer and completely resected carcinoma in situ of any type Subjects with known serious cardiovascular diseases, congenital long QT syndrome, torsade de pointes, myocardial infarction in the past 6 months, or arterial thrombosis, or unstable angina pectoris, or congestive heart failure which is classified as New York Heart Association (NYHA) class 3 or higher, or left ventricular ejection fraction (LVEF) < 50%, QTcF > 450 ms Subjects with uncontrolled medical conditions that could compromise participation in the study(e.g. uncontrolled hypertension, hypothyroidism, diabetes mellitus) Known diagnosis of human immunodeficiency virus(HIV) , hepatitis C, active hepatitis B, treponema pallidum (testing is not mandatory） Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal. Estimated glomerular filtration rate (eGFR) < 30 ml/min Severe kidney disease requiring dialysis Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception, as shown below, throughout the study and for 3 months after stopping GT0918 treatment. Highly effective contraception methods include: Total Abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, or Use of one of the following combinations (a+b or a+c or b+c): Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. Placement of an intrauterine device (IUD) or intrauterine system (IUS) ; Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository ; Female sterilization (have had prior surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment ; Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient; In case of use of oral contraception women should have been stable for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, is she considered not of child bearing potential; Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping GT0918 treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid Subject likely to transfer to another hospital within the next 28 days Subject (or legally authorized representative) not willing or unable to provide informed consent

Proxalutamide + usual care as determined by care provider Proxalutamide: Proxalutamide 300mg q.d

Proxalutamide

CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2F)C(=S)N1c1ccc(CCCc2ncco2)nc1

NCT04737187

NCT04737187_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded). RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy. Has received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen. Has measurable or non-measurable disease as defined by RECIST version 1.1 Is able to swallow oral tablets. Estimated life expectancy ≥12 weeks. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 Exclusion Criteria: More than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer. Pregnancy, lactating female or possibility of becoming pregnant during the study. Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization. Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation). Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease. Has severe or uncontrolled active acute or chronic infection. Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. Known Hepatitis B or Hepatitis C Virus infection. Known carriers of HIV antibodies. Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia. Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization. Treatment with any of the following within the specified time frame prior to randomization: major surgery within 4 weeks prior to randomisation (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study Prior radiotherapy if completed less than 4 weeks before randomisation, except if provided as a short course for symptoms palliation only. Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks prior to randomization Other clinically significant medical conditions. Other malignancies.

Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.

5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1H-pyrimidine-2,4-dione;1-[(5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione;hydrochloride

Cl.N=C1CCCN1Cc1[nH]c(=O)[nH]c(=O)c1Cl.O=c1[nH]c(=O)n(C2CC(O)C(CO)O2)cc1C(F)(F)F.O=c1[nH]c(=O)n(C2CC(O)C(CO)O2)cc1C(F)(F)F

NCT04737278

NCT04737278_EG000

No

All

Adult | Older Adult

Phase 1 | Phase 2

Inclusion Criteria: Male or female age 18-75 If female, subject is not of child bearing potential. Defined as females who have had a hysterectomy or oophorectomy. bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation). Female subject of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo--Provera, Lunelle), or hormone implant (Norplant System), Intrauterine devices, Vasectomy of partner, Total Abstinence Subject has unresolved persistent muscle or nerve pain (muscle or nerve pain population) Subjects using other therapies for nerve/muscle pain (e.g., exercise, TENS, acupuncture, exercise, psychotherapy, massage, physiotherapy, etc), must be used at a stable schedule for 1 month prior to the trial and subject agrees to continue these therapies at the same schedule during the trial avoiding changes in frequency or intensity and to record therapies in the study diary Agrees to comply with study procedures Has given voluntary, written, informed consent to participate in the study Exclusion Criteria: Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial Planned surgery during the course of the trial Use of prescription drugs for fibromyalgia or nerve pain (e.g.Lyrica, Cymbalta and Savella and others). Use of prescription medications for depression, anxiety or other mental disorders Requires the use of prescription drugs to control pain (other than provided rescue medication) Use of oral or topical prescription or over the counter medications or natural health products for pain relief 3 days prior to randomization and during the trial (other than provided rescue medication) Use of natural health products including vitamins and minerals within 3 days prior to randomization and during the trial Use of blood thinning medications (e.g. warfarin) Chronic lyme disease or chronic parasitic infections Uncontrolled hypertension defined as untreated systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg Subjects with diabetes History of bleeding disorders, or significant blood loss in the past 3 months Alcohol use >2 standard alcoholic drinks per day and/or alcohol or drug abuse within the past year Allergy or sensitivity to study supplement ingredients or acetaminophen Participation in a clinical research trial within 30 days prior to randomization Individuals who are cognitively impaired and/or who are unable to give informed consent Any other condition which in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may pose significant risk to the subject

Cunermuspir (Copper Niacin Chelate) 6.06mg per capsule. Non--medicinal ingredients: Organic evaporated cane juice powder, hypromellose, titanium dioxide Two doses per day: one with the morning meal and the other with a mid afternoon snack. The study duration was 28 days. Cunermuspir: Copper Niacin Chelate, 6.06 mg per capsule Non-medicinal ingredients: Organic evaporated cane juice powder, hypromellose, titanium dioxide

Cunermuspir

O=C([O-])c1cccnc1.[Cu+]

NCT04738318

NCT04738318_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria • All adults ≥18 years old with an isolated, intra-articular traumatic elbow fracture to be treated at Vanderbilt University Medical Center with operative intervention and a standardized post-operative rehab protocol. Intra-articular elbow fracture defined as: Distal humerus Proximal ulna Radial head fracture Combination fracture of two or more of the above Radiographs present confirming intra-articular injury Exclusion Criteria Patients with bilateral elbow fractures Patients with an altered mental status Pregnant Allergy or contra-indication to glucocorticoid administration Type 1 or Type 2 diabetes Pre-injury limitation in elbow range or motion (patient reported) Unable to provide consent for themselves

Patients will receive a single intraoperative dose of 10mg of intravenous dexamethasone. Following surgery, the participant will be provided with a 1) six-day oral methylprednisolone taper course. Glucocorticoids: Patients will receive a single intraoperative dose of 10mg of intravenous dexamethasone intraoperatively. Following surgery, the participant will be provided with a six-day oral methylprednisolone taper course.

Betamethasone

CC1CC2C3CCC4=CC(=O)C=CC4(C)C3(F)C(O)CC2(C)C1(O)C(=O)CO

A01AC02 | A07EA04 | C05AA05 | C05AA09 | D07AB19 | D07AC01 | D07BC01 | D07CB04 | D07CC01 | D07XB05 | D07XC01 | D10AA03 | H02AB01 | H02AB02 | R01AD03 | R01AD06 | R01AD53 | R03BA04 | S01BA01 | S01BA06 | S01BB04 | S01CA01 | S01CA05 | S01CB01 | S01CB04 | S02BA06 | S02BA07 | S02CA06 | S03BA01 | S03BA03 | S03CA01 | S03CA06

NCT04738318

NCT04738318_EG001

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria • All adults ≥18 years old with an isolated, intra-articular traumatic elbow fracture to be treated at Vanderbilt University Medical Center with operative intervention and a standardized post-operative rehab protocol. Intra-articular elbow fracture defined as: Distal humerus Proximal ulna Radial head fracture Combination fracture of two or more of the above Radiographs present confirming intra-articular injury Exclusion Criteria Patients with bilateral elbow fractures Patients with an altered mental status Pregnant Allergy or contra-indication to glucocorticoid administration Type 1 or Type 2 diabetes Pre-injury limitation in elbow range or motion (patient reported) Unable to provide consent for themselves

Patients will receive a single intraoperative dose of 10 mg of saline. Following surgery, the participant will be provided with a six-day placebo course. Saline: Patients will receive a single intraoperative dose of 10 mg of saline. Following surgery, the participant will be provided with a six-day placebo course.

SODIUM CHLORIDE

[Cl-].[Na+]

A12CA01 | B05CB01 | B05XA03 | S01XA03

NCT04739865

NCT04739865_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Signed ICF. 18 years of age or older At least moderate MDD Hamilton Depression Rating Scale (17 item) score ≥18 Currently receiving treatment with a selective serotonin reuptake inhibitor Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatments McLean Screening Instrument for Borderline Personality Disorder <7 at Screening (V1). Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits. Exclusion Criteria: Psychiatric Exclusion Criteria: Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, as assessed by medical history, McLean Screening Instrument for Borderline Personality Disorder and a structured clinical interview (version 7.0.2 MINI). Prior electroconvulsive therapy and/or ketamine for current episode. Ongoing use of an antidepressant medication, including augmentation or combination therapies, other than a single SSRI Current psychological therapies that will not remain stable within 21 days of the psilocybin session. Psychological therapies cannot be initiated within 21 days of baseline. Current (within the last year) alcohol or substance use disorder as informed by DSM 5 (diagnosed by MINI 7.0.2) at Screening (V1). Significant suicide risk as defined C-SSRS within the past year Depression secondary to other severe medical conditions according to clinicians' judgement. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin, including exposure to psilocybin within the past year and use of psychedelics, such as ayahuasca, during the current depressive episode. General Medical Exclusion Criteria: Women who are pregnant, nursing or planning a pregnancy. Cardiovascular conditions Uncontrolled or insulin dependent diabetes. Seizure disorder. Positive urine drug screen for illicit drugs or drugs of abuse Current enrolment in any investigational drug or device study or participation in such within 30 days prior to Screening (V1). Current enrolment in another clinical study of an investigational medical or participation in such within 30 days of Screening (V1). Abnormal and clinically significant results on the physical examination, vital signs, ECG or laboratory tests at Screening (V1). Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study.

25 mg COMP360 Psilocybin Psilocybin: Open label

Psilocybin

CN(C)CCc1c[nH]c2cccc(OP(=O)(O)O)c12

NCT04740827

NCT04740827_EG001

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: At least a 1-year history of migraine with or without aura consistent with a diagnosis according to the ICHD-3, 2018. Age of the participant at the time of migraine onset < 50 years -History of 4 to 14 migraine days per month on average in the 3 months prior to Visit 1 in the investigator's judgment Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. 4 to 14 migraine days in the 28-day baseline period per eDiary Failed oral migraine prophylaxis medications from 2 to 4 medication classes Exclusion Criteria: Any clinically significant hematologic, endocrine, pulmonary, hepatic, gastrointestinal, or neurologic disease Participant has any other concurrent pain condition that, in the opinion of the investigator, may significantly impact the current headache disorder In the opinion of the investigator, confounding psychiatric conditions, dementia, epilepsy, or significant neurological disorders other than migraine Has ≥ 15 headache days per month on average across the 3 months prior to Visit 1 in the investigator's judgment Has ≥ 15 headache days in the 28-day baseline period per eDiary Clinically significant cardiovascular or cerebrovascular disease Has a history of migraine accompanied by diplopia or decreased level of consciousness or retinal migraine as defined by ICHD-3, 2018 Has a current diagnosis of chronic migraine, new persistent daily headache, medication overuse headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3, 2018

Participants received atogepant 60 mg, orally, QD for up to 12 weeks in a DB treatment period.

Atogepant

C[C@@H]1[C@H](c2c(F)ccc(F)c2F)C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N1CC(F)(F)F

N02CD07

NCT04741074

NCT04741074_EG000

No

All

Adult | Older Adult

Phase 3

Inclusion Criteria: - Age ≥ 18 years - BMI 25-45 kg/m2 - T2DM - Advanced CKD* (last eGFR <30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to <45 ml/min/1.73m2 with albumin/creatinine ratio >30 mg/g). - Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes [A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference >120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers]. - Ability to provide informed consent before any trial-related activities - Access to a telephone The cause of the CKD does not need to be due specifically to diabetes Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers) - Active malignancy - History of pancreatitis - Active substance abuse - Severe COPD - Pulmonary fibrosis - Symptomatic angina or recent myocardial infarction within 6 months - Severe peripheral vascular disease - Cirrhosis - New York Health Association (NYHA) Class III-IV congestive heart failure - Severe cognitive impairment - Drug addiction - History of non-adherence to therapy - Active infection - Expected life expectancy < 5 years Additional exclusion criteria - Type 1 diabetes mellitus - History of diabetic ketoacidosis within the last 12 months - Planning on undergoing bariatric surgery in next 9 months. - Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures - Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking - Psychiatric hospitalization in past year - Principal investigator discretion (i.e. concerns about safety, compliance) - Known or suspected allergy to trial medication - Previous participation (i.e. randomized) in this trial - Use of GLP1-RA or pramlintide within 90 days prior to screening - Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2) - Use of DPP-4 inhibitors within 30 days prior to screening - Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome - Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening

This arm will receive semaglutide. Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution: Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.

Semaglutide

CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C

A10BJ06

NCT04746963

NCT04746963_EG000

No

All

Adult | Older Adult

Phase 1 | Phase 2

Inclusion Criteria: Patients 50 years of age or older diagnosed in the study eye with subfoveal choroidal neovascularization (CNV) or juxtafoveal CNV secondary to AMD Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 65 to 10 in the study eye Willing and able to comply with clinic visits and study-related procedures Provide signed inform consent Exclusion Criteria: Macular edema or CMV secondary to any causes other than AMD in the study eye Previously-treated patients who are not responders to anti-VEGF Any condition that may preclude improvement in visual acuity in the study eye Previous vitreoretinal surgery, filtration surgery, and cataract surgery within 3 months in the study eye Note: Other inclusion/exclusion criteria apply

AXT107 0.1 mg/eye AXT107 0.1 mg: Single intravitreal injection of AXT107 0.1 mg/eye (low dose)

Gersizangitide

CCC(C)C(NC(=O)C(CC(=O)O)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(C)NC(=O)C(Cc1ccccc1)NC(=O)C1CCCN1C(=O)C(C)NC(=O)C(NC(=O)C(CO)NC(=O)C(Cc1ccccc1)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(N)CC(C)C)C(C)O)C(C)CC)C(=O)NC(CC(N)=O)C(=O)NC(CC(=O)O)C(=O)NC(C(=O)NC(C(=O)NC(CC(N)=O)C(=O)NC(Cc1ccccc1)C(N)=O)C(C)CC)C(C)C

NCT04748783

NCT04748783_EG002

Accepts Healthy Volunteers

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: Diagnosed SARS-CoV-2+ status. Either became symptomatic in the prior 7 days, or if not symptomatic, likely infected/exposed within the prior 7 days. All patients listed from the University of North Carolina at Chapel Hill (UNC) Respiratory Diagnostic Center (RDC) have a confirmed SARS-CoV-2 infection and have consented to be contacted for research purposes. For patients contacting study coordinators for enrollment, who were not tested in the RDC, they must provide written proof of positive SARS-CoV-2 status in the prior 7 days. Individuals (all sex, all gender) at least 18 years of age and at most 65 years of age and in good oral health without any known allergies to commercial dental products or cosmetics. American Society of Anaesthesiologists (ASA) class I or II prior to SARS-CoV-2 infection. Evidence of a personally signed and dated informed consent document indicating the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial and all of their questions have been answered. Able to comprehend and follow the requirements of the study (including availability on scheduled visit dates) based on research site personnel's assessment. Females of childbearing potential will have a negative urine pregnancy test (on site) or be physically incapable of pregnancy (implants or injections, Intrauterine device, Bilateral tubal ligation, Hysterectomy, Ovariectomy, Women post-menopausal) Exclusion Criteria: Subjects presenting with any of the following will not be included in the study: Patients who have been eating or drinking within an hour of the study Patients under 18 years of age and older than 65 years of age Subjects presenting with and/or self-reporting any of the following will not be included in the study: history of significant adverse effects following use of oral hygiene products such as toothpastes and mouthrinses. (self-reported) Self-reported allergy to hydrogen peroxide, peroxyl, chlorhexidine gluconate, periogard, peridex, colgate total zero, colgate total, cetylpyridinium chloride, essential oils (Eucalyptol, Menthol, Methyl salicylate, Thymol), and other components in the mouth rinses (methyl salicylate, ethanol, saccharin sodium, glycerin, propylene glycol, sorbitol, Federal Food, Drug, and Cosmetic (FD&C) blue additive no. 1, Poloxamer 407, Benzoic acid, Zinc chloride, Sodium benzoate, Sucralose, Polyethylene Glycol (PEG-40) sorbitan diisostearate, potassium sorbate, citric acid). History of serious medical conditions that, at the discretion of the Investigator, will disqualify the subject. (Self-reported) A history of severe dry mouth (xerostomia), severe drug-induced xerostomia (antidepressants, anticonvulsants, antihypertensives), or Sjogren's syndrome A history of recent (within the last 30 days) or current recent oral herpes flare up, candida (thrush) infection, apthous ulcer flare up, current/active severe periodontal disease, or other recent oral viral infection or flare up within the past 30 days (self-reported) Current history of alcohol or drug abuse (self-reported). History of drinking water or eating food within an hour of the study visit. History of drinking alcohol within 12 hours of the study visit. History of using a commercial mouthrinse within 24 hours of the study visit. Participation in any study involving oral care products, concurrently or within the previous 30 days. (self-reported) Positive pregnancy test reported pregnancy or lactation (this criterion is due to oral tissue changes related to pregnancy and nursing which can affect interpretation of study results. Additionally, women are advised to check with their physician before using Chlorhexidine Gluconate during pregnancy and lactation, which cannot occur in a blinded, randomized trial.) Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this trial. Patient with developmental/cognitive disability that cannot self-consent, comprehend and follow the requirements of the study based on research site personnel's assessment. Patients with sizable mucosal tears, abrasions, growths or burns in the mouth Patients with kidney dysfunction

Subject participants will rinse mouth one time for 60 seconds with 10 mL Periogard (0.12% Chlorhexidine Gluconate) rinse.

CID 12303048

NC(=NCCCCCCN=C(N)N=C(N)Nc1ccc(Cl)cc1)N=C(N)Nc1ccc(Cl)cc1.O=C(O)C(O)C(O)C(O)C(O)CO.O=C(O)C(O)C(O)C(O)C(O)CO

S03AA04

NCT04749797

NCT04749797_EG000

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: ≥18 years of age Need for elective supratentorial craniotomy Preoperative GCS > 13 Exclusion Criteria: Preoperative GCS ≤ 13 Child (<18 years of age) Inability to understand or use the visual analog scale (VAS) Proven or suspected allergy to local anesthetics Craniotomy incision extending beyond the field of the block Patients chronically (more than 2 wk) treated with narcotic medications Previous scalp incision Bilateral craniotomies Allergies to local anesthetics GCS verbal score < 4 after extubation Patients whose surgeries extend past 6 hours (will be placed on standard of care and removed from study) Patients currently on ergot-type oxytoxic drugs, MAOIs, or certain antidepressants Lactating Mothers

The surgeon will administer injectable saline as a cranial block according to a technique previously described by Pinosky et al (Pinosky et al., 1996). The supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, postauricular lesser and greater occipital nerve branches on the ipsilateral side of the operation will be blocked with 5-10 cc of solution (with a maximum of 60 cc at all sites) by needle infiltration. This process generally takes 1-2 minutes. Following this, the general anesthesia is lightened and the patient is extubated in usual fashion. Saline: Used as cranial block for craniotomy surgery

SODIUM CHLORIDE

[Cl-].[Na+]

A12CA01 | B05CB01 | B05XA03 | S01XA03

NCT04749797

NCT04749797_EG001

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: ≥18 years of age Need for elective supratentorial craniotomy Preoperative GCS > 13 Exclusion Criteria: Preoperative GCS ≤ 13 Child (<18 years of age) Inability to understand or use the visual analog scale (VAS) Proven or suspected allergy to local anesthetics Craniotomy incision extending beyond the field of the block Patients chronically (more than 2 wk) treated with narcotic medications Previous scalp incision Bilateral craniotomies Allergies to local anesthetics GCS verbal score < 4 after extubation Patients whose surgeries extend past 6 hours (will be placed on standard of care and removed from study) Patients currently on ergot-type oxytoxic drugs, MAOIs, or certain antidepressants Lactating Mothers

The surgeon will administer bupivacaine as a cranial block according to a technique previously described by Pinosky et al (Pinosky et al., 1996). The supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, postauricular lesser and greater occipital nerve branches on the ipsilateral side of the operation will be blocked with 5-10 cc of solution (with a maximum of 60 cc at all sites) by needle infiltration. This process generally takes 1-2 minutes. Following this, the general anesthesia is lightened and the patient is extubated in usual fashion. Bupivacaine Injection: Used as cranial block for craniotomy surgery

Bupivacaine

CCCCN1CCCCC1C(=O)Nc1c(C)cccc1C

N01BB01 | N01BB10 | N01BB51 | N01BB59

NCT04749797

NCT04749797_EG002

No

All

Adult | Older Adult

Phase 4

Inclusion Criteria: ≥18 years of age Need for elective supratentorial craniotomy Preoperative GCS > 13 Exclusion Criteria: Preoperative GCS ≤ 13 Child (<18 years of age) Inability to understand or use the visual analog scale (VAS) Proven or suspected allergy to local anesthetics Craniotomy incision extending beyond the field of the block Patients chronically (more than 2 wk) treated with narcotic medications Previous scalp incision Bilateral craniotomies Allergies to local anesthetics GCS verbal score < 4 after extubation Patients whose surgeries extend past 6 hours (will be placed on standard of care and removed from study) Patients currently on ergot-type oxytoxic drugs, MAOIs, or certain antidepressants Lactating Mothers

The surgeon will administer Exparel (liposomal bupivacine) as a cranial block according to a technique previously described by Pinosky et al (Pinosky et al., 1996). 20 mL of Exparel will be diluted with saline to constitute 60 mL total. The supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, postauricular lesser and greater occipital nerve branches on the ipsilateral side of the operation will be blocked with 5-10 cc of solution (with a maximum of 60 cc at all sites) by needle infiltration. This process generally takes 1-2 minutes. Following this, the general anesthesia is lightened and the patient is extubated in usual fashion. Liposomal bupivacaine: Used as cranial block for craniotomy surgery

Bupivacaine

CCCCN1CCCCC1C(=O)Nc1c(C)cccc1C

N01BB01 | N01BB10 | N01BB51 | N01BB59

NCT04752475

NCT04752475_EG000

No

Female

Adult | Older Adult

Phase 3

Inclusion Criteria: Postpartum women No antenatal diagnosis of hypertensive disorder of pregnancy at the time of admission for delivery, defined as existing chronic hypertension diagnosis or documented blood pressure of ≥140 systolic OR ≥90 diastolic on at least 2 occasions at least 4 hours apart prior to delivery admission who do not go on to get magnesium for seizure prophylaxis by the time of delivery At least 18 years of age English or Spanish speakers One or more high risk factors for development of de novo postpartum hypertension Exclusion Criteria: Non-English or Spanish speakers Women with a contraindication to diuretic therapy Women who have used diuretics in the two weeks prior to delivery

Furosemide 20 mg, oral, once daily for 5 days Furosemide: Furosemide 20 mg pill taken daily for 5 days

Furosemide

NS(=O)(=O)c1cc(C(=O)O)c(NCc2ccco2)cc1Cl

C03CA01 | C03CB01 | C03EB01 | G01AE10

NCT04753164

NCT04753164_EG000

No

All

Adult

Phase 2

Inclusion Criteria: Criteria assessed at Visit 1: Signed and dated informed consent form prior to any study-mandated procedure. Male or female study participants aged 18 to 55 years at the time of signing the informed consent form. Binge-eating disorder (BED) in accordance with Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria diagnosed using the Structured Clinical Interview for DSM-5 (SCID-5). Self-reported BED severity of at least moderate level, defined as at least 4 BE episodes per week, on average, for a duration of at least 6 months. BED in accordance with Eating Disorder Examination Questionnaire (EDE-Q). Clinical Global Impression of Severity scale (CGI-S) score of ≥ 4. For women of childbearing potential (WOCBP): Negative serum pregnancy test at Visit 1; agreement to undertake monthly urine or serum pregnancy tests during the study and up to the EOS visit; agreement to use an acceptable contraceptive method. Criteria assessed at Visit 2: Reporting ≥3 BE days for each of the 2 weeks prior to randomization as documented in the participant's BE diary and with BE diary entries completed for at least 6 days per week during this 2-week period (between Visit 1 and 2). CGI-S score of ≥ 4. For WOCBP: negative urine pregnancy test. Exclusion Criteria: Criteria assessed at Visit 1: BMI < 18.0 kg/m² or > 45 kg/m². Any acute or chronic-persistent psychiatric disorder other than BED diagnosed in the past, including anorexia nervosa, bulimia, psychotic disorders, bipolar disorder, hypomania, or dementia, as defined by the DSM-5 criteria or by the Mini International Neuropsychiatric Interview (MINI©). Use of any medications for the treatment of BED (including lisdexamfetamine [Vyvanse®]), any other eating disorder, obesity, or weight gain, or any other medication that could result in weight gain or weight loss, including over-the-counter and herbal products, within 3 months prior to Screening. Any clinically unstable medical condition, significant medical disorder or acute illness that, in the investigator's opinion, could interfere with the participants ability to comply with study assessments or abide by study restrictions. Criteria assessed at Visit 1 and Visit 2 HAMD-17 score ≥ 17 points at Visit 1 and/or Visit 2. Any of the following conditions related to suicidality: Participant is considered to have a suicide risk in the investigator's opinion or has a previous history of suicide attempt within the past 12 months. Participant answers "yes" to "suicidal ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS© assessment at Screening (in the past month). Participants who answer "yes" to this question must be referred to the investigator for follow-up evaluation. Female participants: pregnant, lactating or planning to become pregnant during the projected course of the study.

ACT-539313: ACT-539313 as capsules at a strength of 100 mg, taken orally, b.i.d. in the morning at breakfast and in the evening at dinner, with a glass of water during the treatment period.

Nivasorexant

Cc1ccc(C(=O)N2CCOCC2Cc2cccc(-n3nccn3)c2)c(-n2nccn2)c1

NCT04756128

NCT04756128_EG000

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Male and (non-pregnant, non-breastfeeding) females aged 18 years or older Requiring admission to Methodist or Regions Hospital due to laboratory-confirmed COVID-19 Meets criteria of only up to moderate COVID-19 disease as defined by a clinical score of 2 or 3 at the time of enrollment, and one or more of the following: Dyspnea limiting usual activities on baseline O2 needs Respiratory rate >/= 30/min on O2 or room air Blood oxygen saturations <94% on room air (or on baseline O2 needs if on supplemental oxygen prior to presentation at the hospital for a condition unrelated to COVID-19). Requiring supplemental 02 above baseline needs (i.e. prior to presentation at hospital) COVID-19 contributed to the current hospital admission, per attending provider's clinical assessment of the patient. Ability to provide written informed consent, or has identifiable LAR that is able to do so on the patient's behalf as defined by study protocol, prior to performing study procedures. Exclusion Criteria: Patients meeting criteria for severe/critical COVID-19 as defined by study protocol or requiring O2 supplementation ≥10L nasal cannula at screening Patients currently in shock as defined by hemodynamic instability requiring vasopressors Patients with a current hospitalization for COVID-19 that is >/=7 days at the time of screening. Clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment Patients in which EITHER symptom onset OR a positive COVID-19 laboratory test occurred >14 days prior to enrollment. Patients with concomitant influenza A or B at time of hospitalization if tested as part of ED/hospital admission. Female patients who are pregnant or breastfeeding at time of hospital admission Diagnosis of Chronic Kidney Disease stage ≥4 as documented in the patient's problem list (not based on CrCI calculations alone) CrCl < 30 mL/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening History of cirrhosis or advanced liver disease, or active hepatic viral infection Transplant of kidney, lung, heart, or liver in the past 2 years Uncontrolled severe gastrointestinal disorders, Crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months Patients currently receiving agents that are p-glycoprotein AND strong CYP3A4 inhibitors with CrCl < 60 mL/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential Colchicine and Naltrexone interactions). Patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies Chronic or current use of colchicine or any mu-opioid antagonist. Chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. Pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, TNF-inhibitors, or JAK inhibitors. NOTE: Patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for COVID-19. Use of tocilizumab at baseline for another indication will continue to be excluded. Participation in any other clinical trial of an experimental treatment for COVID-19, note: While convalescent plasma is no longer recommended within HP, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; Patients previously enrolled in the C3PO study can enroll in this study, as any convalescent plasma received would have been outpatient; Remdesivir is allowed per standard protocol; Dexamethasone is allowed per standard protocol Patients actively enrolled in hospice or that are DNI or on palliative care History of hypersensitivity reaction to colchicine or its inactive ingredients History of hypersensitivity reaction to naltrexone or its inactive ingredients Incarcerated or a ward of the state Any patient considered an unsuitable candidate, for any reason, by study investigators.

Patients randomized to a colchicine-containing treatment arm will receive colchicine 0.6 mg twice daily for up to 28 days. Patients experiencing gastrointestinal side effects (nausea, vomiting, and diarrhea) on twice daily dosing may have the dose decreased to 0.6 mg daily. Dosing will continue twice daily unless there is a change that requires a dose adjustment or an exclusion criterion is met. Dosing deviations above the study protocol will be allowed if medically necessary for the treatment of an additional indication (e.g. colchicine for viral pericarditis). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production.

Colchicine

COc1cc2c(c(OC)c1OC)-c1ccc(OC)c(=O)cc1[C@@H](NC(C)=O)CC2

M04AC01

NCT04756128

NCT04756128_EG002

No

All

Adult | Older Adult

Phase 2

Inclusion Criteria: Male and (non-pregnant, non-breastfeeding) females aged 18 years or older Requiring admission to Methodist or Regions Hospital due to laboratory-confirmed COVID-19 Meets criteria of only up to moderate COVID-19 disease as defined by a clinical score of 2 or 3 at the time of enrollment, and one or more of the following: Dyspnea limiting usual activities on baseline O2 needs Respiratory rate >/= 30/min on O2 or room air Blood oxygen saturations <94% on room air (or on baseline O2 needs if on supplemental oxygen prior to presentation at the hospital for a condition unrelated to COVID-19). Requiring supplemental 02 above baseline needs (i.e. prior to presentation at hospital) COVID-19 contributed to the current hospital admission, per attending provider's clinical assessment of the patient. Ability to provide written informed consent, or has identifiable LAR that is able to do so on the patient's behalf as defined by study protocol, prior to performing study procedures. Exclusion Criteria: Patients meeting criteria for severe/critical COVID-19 as defined by study protocol or requiring O2 supplementation ≥10L nasal cannula at screening Patients currently in shock as defined by hemodynamic instability requiring vasopressors Patients with a current hospitalization for COVID-19 that is >/=7 days at the time of screening. Clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment Patients in which EITHER symptom onset OR a positive COVID-19 laboratory test occurred >14 days prior to enrollment. Patients with concomitant influenza A or B at time of hospitalization if tested as part of ED/hospital admission. Female patients who are pregnant or breastfeeding at time of hospital admission Diagnosis of Chronic Kidney Disease stage ≥4 as documented in the patient's problem list (not based on CrCI calculations alone) CrCl < 30 mL/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening History of cirrhosis or advanced liver disease, or active hepatic viral infection Transplant of kidney, lung, heart, or liver in the past 2 years Uncontrolled severe gastrointestinal disorders, Crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months Patients currently receiving agents that are p-glycoprotein AND strong CYP3A4 inhibitors with CrCl < 60 mL/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential Colchicine and Naltrexone interactions). Patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies Chronic or current use of colchicine or any mu-opioid antagonist. Chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy. Pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, TNF-inhibitors, or JAK inhibitors. NOTE: Patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for COVID-19. Use of tocilizumab at baseline for another indication will continue to be excluded. Participation in any other clinical trial of an experimental treatment for COVID-19, note: While convalescent plasma is no longer recommended within HP, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment; Patients previously enrolled in the C3PO study can enroll in this study, as any convalescent plasma received would have been outpatient; Remdesivir is allowed per standard protocol; Dexamethasone is allowed per standard protocol Patients actively enrolled in hospice or that are DNI or on palliative care History of hypersensitivity reaction to colchicine or its inactive ingredients History of hypersensitivity reaction to naltrexone or its inactive ingredients Incarcerated or a ward of the state Any patient considered an unsuitable candidate, for any reason, by study investigators.

Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. The first dose can be given at any time during the day of enrollment/randomization, and will be timed at 08:00 daily thereafter (with AM colchicine dose, if in combined colchicine/LDN arm) for up to 28 days (unless new contraindication or exclusion criteria met). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent that has been shown to reduce symptom severity in fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. For this study, patients enrolled in a naltrexone-containing arm will take their daily dose of the medication (4.5mg) by oral suspension.

Naltrexone

[H][C@@]12Oc3c(O)ccc4c3[C@@]13CCN(CC1CC1)[C@]([H])(C4)[C@]3(O)CCC2=O

A08AA62 | N02AA56 | N07BB04

NCT04756154

NCT04756154_EG002

Accepts Healthy Volunteers

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Subjects of any race Subjects in good health Minimum skin flora baseline requirements on inguinal region Exclusion Criteria: Any tattoos, scars, breaks in the skin, or any form of dermatitis, or other skin disorders (including acne) on the applicable test area Topical antimicrobial exposure within 14 days prior to screening and treatment days Use of systemic or topical antibiotics, steroid medications, or any other products known to affect the normal microbial flora of the skin within 14 days prior to screening and treatment days

Apply topically to the inguinal region for 2 minutes

SODIUM CHLORIDE

[Cl-].[Na+]

A12CA01 | B05CB01 | B05XA03 | S01XA03

NCT04756804

NCT04756804_EG000

Accepts Healthy Volunteers

All

Adult | Older Adult

Phase 3

Inclusion Criteria: Be male or female and at least 18 years of age. Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English. Be planning to undergo clean (class I wound) or clean-contaminated (class II wounds) surgery. Expect to be available for up to 30-days after the surgery. Exclusion Criteria: Active infection or fever including evidence of infection at or adjacent to the operative site. Immunosuppressed. Kidney/liver failure. Immunosuppressive therapy (chemotherapy, steroids) within the previous 1 week. Any history of allergy to chlorhexidine or isopropyl alcohol or any other component in ZuraGard including citric acid, sodium citrate, methylparaben, or propylparaben, and FD&C Yellow #6.

70% v/v Isopropyl Alcohol novel preoperative skin antisepsis preparation 70% v/v Isopropyl Alcohol Surgical Solution: Patient preoperative skin preparation

ISOPROPYL ALCOHOL

CC(C)O

D08AX05