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WO2022067185A1 - Méthodes de traitement du cancer de la prostate à effets secondaires minimes - Google Patents

Méthodes de traitement du cancer de la prostate à effets secondaires minimes Download PDF

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Publication number
WO2022067185A1
WO2022067185A1 PCT/US2021/052209 US2021052209W WO2022067185A1 WO 2022067185 A1 WO2022067185 A1 WO 2022067185A1 US 2021052209 W US2021052209 W US 2021052209W WO 2022067185 A1 WO2022067185 A1 WO 2022067185A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
subject
day
prostate cancer
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2021/052209
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English (en)
Inventor
Mitchell Steiner
Gary K. BARNETTE
Robert Getzenberg
Domingo Rodriguez
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Veru Inc
Original Assignee
Veru Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Veru Inc filed Critical Veru Inc
Publication of WO2022067185A1 publication Critical patent/WO2022067185A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/29—Antimony or bismuth compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • ADT androgen deprivation therapy
  • hematologic toxicities e.g., neutropenias including febrile neutropenias, thrombocytopenias, etc.
  • neurotoxicities e.g., neuropathies including peripheral neuropathy which
  • Another embodiment of the invention encompasses methods wherein the amount of Compound 17ya is any of about 4.5 mg, 9 mg, 14 mg, 18 mg, 23 mg, 27 mg, 32 mg, 36 mg, 41 mg, 45 mg, 54 mg, 63 mg, 72 mg, or 81 mg.
  • the dose is a daily dose.
  • An embodiment of the invention encompasses methods wherein the subject is dosed to yield an AUCinf of less than 1950 hr*ng/mL.
  • Another embodiment of the invention encompasses wherein the dose is oral and taken once, twice, or thrice daily.
  • the present invention maximizes drug delivery in a therapeutically effective window while concurrently increasing patient tolerance and minimizing undesirable side effects.
  • many of the anticipated side effects associated with prostate cancer treatment are absent, including neutropenia, neurotoxicity, and/or myelosuppression, while side effects associated with the drug delivery method are minimal to nonexistent based on the dose and/or dosage regimen.
  • the invention encompasses methods of treating a subject with prostate cancer by administering Compound 17ya to yield an AUCinf of about 61.9 hr*ng/mL to about 3342 hr*ng/mL, whereby the subject does not experience neutropenias, neurotoxicities, or gastrointestinal toxicities.
  • the method includes an AUCinf of about 140 hr*ng/mL to about 2506.5 hr*ng/mL.
  • the method yields an AUCinf of about 278.5 hr*ng/mL to about 2228 hr*ng/mL.
  • Suitable pharmaceutically-acceptable salts of amines of compounds used in the method of the invention may be prepared from an inorganic acid or from an organic acid.
  • examples of inorganic salts of amines are bisulfates, borates, bromides, chlorides, hemisulfates, hydrobromates, hydrochlorates, 2-hydroxyethylsulfonates (hydroxyethanesulfonates), iodates, iodides, isothionates, nitrates, persulfates, phosphate, sulfates, sulfamates, sulfanilates, sulfonic acids (alkylsulfonates, arylsulfonates, halogen substituted alkylsulfonates, halogen substituted arylsulfonates), sulfonates and thiocyanates.
  • organic salts of amines include, but are not limited to, aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are acetates, arginines, aspartates, ascorbates, adipates, anthranilates, algenates, alkane carboxylates, substituted alkane carboxylates, alginates, benzenesulfonates, benzoates, bisulfates, butyrates, bicarbonates, bitartrates, citrates, camphorates, camphorsulfonates, cyclohexylsulfamates, cyclopentanepropionates, calcium edetates, camsylates, carbonates, clavulanates, cinnamates, dicarboxylates, digluconates, dodecylsulfonates, dihydrochlorides, decanoates,
  • the salts may be formed by conventional means, such as by reacting the free base or free acid form of the product with one or more equivalents of the appropriate acid or base in a solvent or medium in which the salt is insoluble or in a solvent such as water, which is removed in vacuo or by freeze drying or by exchanging the ions of an existing salt for another ion or suitable ionexchange resin.
  • a maintenance dose of a compound, composition or formulation may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level. Subjects may, however, require intermittent treatment on a long-term basis upon any recurrence of disease symptoms.
  • the solid unit dosage forms can be of the conventional type.
  • the solid form can be a capsule and the like, such as an ordinary gelatin type containing the compounds and a carrier.
  • an estimated AUCinf (AUCo-24h or AUCo-t) was determined to be: 1671 hr*ng/mL for a dose of 54 mg of Compound 17ya; 1949 hr*ng/mL for a dose of 63 mg of Compound 17ya; and 2228 hr*ng/mL for a dose of 72 mg of Compound 17ya.
  • FIG. 4A illustrates a screening CT scan: the right anterior psoas muscle cancerous lymph node (1.7 cm X 1.5 cm).
  • Figure 4A illustrates a screening CT scan 8 months later: the right anterior psoas muscle cancerous lymph node (1.1 cm X 1.0 cm).
  • Figure 4B illustrates a coronal CT scan on day one of treatment (left panel) and after 15 months of treatment (right panel), which resulted in about - 33% growth (or 33% regression) of the tumor.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des méthodes de traitement du cancer de la prostate par l'administration du Composé 17ya sans induire ou minimiser les effets secondaires indésirables.
PCT/US2021/052209 2020-09-27 2021-09-27 Méthodes de traitement du cancer de la prostate à effets secondaires minimes Ceased WO2022067185A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063083955P 2020-09-27 2020-09-27
US63/083,955 2020-09-27

Publications (1)

Publication Number Publication Date
WO2022067185A1 true WO2022067185A1 (fr) 2022-03-31

Family

ID=80846928

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/052209 Ceased WO2022067185A1 (fr) 2020-09-27 2021-09-27 Méthodes de traitement du cancer de la prostate à effets secondaires minimes

Country Status (1)

Country Link
WO (1) WO2022067185A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114805307A (zh) * 2022-04-29 2022-07-29 南京雷正医药科技有限公司 一种用于制备冠状病毒治疗药物的吲哚类化合物
US20230348433A1 (en) * 2022-04-28 2023-11-02 Veru Inc. Polymorphs of [2-(1h-indol-3-yl)-1h-imidazol-4-yl](3,4,5-trimethoxy)methanone and its salts

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004056971A2 (fr) * 2002-12-19 2004-07-08 Genta Incorporated Methodes de traitement d'un trouble associe au bcl-2 a l'aide d'oligomeres anti-sens bcl-2
US20090181944A1 (en) * 2008-01-11 2009-07-16 John Frederick Boylan Method for cancer therapy
US20150374717A1 (en) * 2013-03-04 2015-12-31 Aventis Pharma S.A. Cabazitaxel and its use for treating metastatic prostate cancers
US20160015688A1 (en) * 2013-03-05 2016-01-21 University Of Tennessee Research Foundation Compounds for treatment of cancer
WO2016145298A1 (fr) * 2015-03-12 2016-09-15 The Regents Of The University Of California Méthodes de traitement du cancer par des inhibiteurs de ror gamma
US20180092930A1 (en) * 2016-09-30 2018-04-05 Janssen Pharmaceutica Nv Methods of diagnosing and treating abiraterone acetate- glucocorticoid -resistant or -sensitive metastatic castration resistant prostate cancer
WO2020157699A1 (fr) * 2019-01-30 2020-08-06 Aragon Pharmaceuticals, Inc. Anti-androgènes pour le traitement du cancer de la prostate métastatique sensible à la castration

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004056971A2 (fr) * 2002-12-19 2004-07-08 Genta Incorporated Methodes de traitement d'un trouble associe au bcl-2 a l'aide d'oligomeres anti-sens bcl-2
US20090181944A1 (en) * 2008-01-11 2009-07-16 John Frederick Boylan Method for cancer therapy
US20150374717A1 (en) * 2013-03-04 2015-12-31 Aventis Pharma S.A. Cabazitaxel and its use for treating metastatic prostate cancers
US20160015688A1 (en) * 2013-03-05 2016-01-21 University Of Tennessee Research Foundation Compounds for treatment of cancer
WO2016145298A1 (fr) * 2015-03-12 2016-09-15 The Regents Of The University Of California Méthodes de traitement du cancer par des inhibiteurs de ror gamma
US20180092930A1 (en) * 2016-09-30 2018-04-05 Janssen Pharmaceutica Nv Methods of diagnosing and treating abiraterone acetate- glucocorticoid -resistant or -sensitive metastatic castration resistant prostate cancer
WO2020157699A1 (fr) * 2019-01-30 2020-08-06 Aragon Pharmaceuticals, Inc. Anti-androgènes pour le traitement du cancer de la prostate métastatique sensible à la castration

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230348433A1 (en) * 2022-04-28 2023-11-02 Veru Inc. Polymorphs of [2-(1h-indol-3-yl)-1h-imidazol-4-yl](3,4,5-trimethoxy)methanone and its salts
US12240834B2 (en) * 2022-04-28 2025-03-04 Veru Inc. Polymorphs of [2-(1H-indol-3-yl)-1H-imidazol-4- yl] (3,4,5-trimethoxyphenyl)methanone and its salts
CN114805307A (zh) * 2022-04-29 2022-07-29 南京雷正医药科技有限公司 一种用于制备冠状病毒治疗药物的吲哚类化合物

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