# US 2021/0330675 A1 · Methods of treating liver disorders or lipid disorders with a thr-beta agonist > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0330675 A1 - Document ID: US20210330675A1 - Status: Published application - Kind: A1 - Application number: 17/369,197 - Filed: 2021-07-07 - Published: 2021-10-28 - Earliest claimed: 2016-10-18 - Assignees: Madrigal Pharmaceuticals, Inc. - Applicants: Madrigal Pharmaceuticals, Inc. - Inventors: Rebecca TAUB - Web page: https://patentgrep.com/patent/US20210330675A1 ## CPC - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 3/06: Antihyperlipidemics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention provides a method for treating a liver disorder or lipid disorder in a subject in need thereof with 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile, a stereoisomer, a salt thereof, or a morphic form thereof. ## Claims ### Claim 1 A method of treating a lipid disorder in a subject in need thereof, the method comprising: (a) performing a first biomarker test on a first biological sample obtained from the subject, wherein the first biomarker test measures a first expression level of a biomarker, the biomarker being sex hormone-binding globulin (SHBG); (b) administering a first dose of 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile (“Compound A”) to the subject daily for a first period of time; (c) performing a second biomarker test on a second biological sample obtained from the subject, wherein the second biomarker test measures a second expression level of SHBG; (d) determining a change or degree of change in the expression level of SHBG based on the results in steps (a) and (c), wherein the change or degree of change is indicative of the subject's sensitivity to Compound A; and (e) administering a second dose of Compound A to the subject for a second period of time based on the sensitivity result from step (d). ### Claim 2 (depends on 1) The method of claim 1, wherein the second dose of Compound A is further determined based on at least one demographic feature of the subject, medication history of the subject, physical information of the subject, a genetic test or a pharmacokinetic test on a biological sample obtained from the subject, a physical examination on the subject, or a combination thereof. ### Claim 3 (depends on 1) The method of claim 1, wherein the lipid disorder is hyperlipidemia or hypercholesterolemia. ### Claim 4 (depends on 1) The method of claim 1, wherein the lipid disorder is hyperlipidemia. ### Claim 5 (depends on 1) The method of claim 1, wherein the lipid disorder is hypercholesterolemia. ### Claim 6 (depends on 1) The method of claim 1, wherein the biological sample is a blood or serum sample. ### Claim 7 (depends on 1) The method of claim 1, wherein the first dose is in the range of about 5 to 300 mg. ### Claim 8 (depends on 1) The method of claim 1, wherein the first dose is about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, or about 200 mg. ### Claim 9 (depends on 1) The method of claim 1, wherein the second dose is in the range of about 5 to 300 mg. ### Claim 10 (depends on 1) The method of claim 1, wherein the second dose is about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, or about 200 mg. ### Claim 11 (depends on 1) The method of claim 1, wherein Compound A is in a morphic form characterized by an X-ray powder diffraction pattern including peaks at about 10.5, 18.7, 22.9, 23.6, and 24.7 degrees 2θ. ### Claim 12 (depends on 1) The method of claim 1, wherein the first period of time is in the range of about 2-21 days. ### Claim 13 (depends on 1) The method of claim 1, wherein Compound A is administered orally. ### Claim 14 (depends on 1) The method of claim 1, wherein the lipid disorder is heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH). ### Claim 15 (depends on 2) The method of claim 2, wherein the pharmacokinetic test comprises measuring a level of a metabolite of Compound A in the biological sample at a predetermined time after the administration of the first dose. ### Claim 16 (depends on 15) The method of claim 15, wherein the metabolite of Compound A comprises M1 having the following structure: ### Claim 17 (depends on 15) The method of claim 15, wherein the predetermined time is at least 20 minutes.