NZ747331B2 - Combinations of linagliptin and metformin - Google Patents

Combinations of linagliptin and metformin

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Publication number
NZ747331B2
NZ747331B2 NZ747331A NZ74733117A NZ747331B2 NZ 747331 B2 NZ747331 B2 NZ 747331B2 NZ 747331 A NZ747331 A NZ 747331A NZ 74733117 A NZ74733117 A NZ 74733117A NZ 747331 B2 NZ747331 B2 NZ 747331B2
Authority
NZ
New Zealand
Prior art keywords
patient
metformin
acceptable salt
pharmaceutically acceptable
stage
Prior art date
Application number
NZ747331A
Other versions
NZ747331A (en
Inventor
Thomas Meinicke
Eynatten Maximilian Von
Original Assignee
Boehringer Ingelheim International Gmbh
Filing date
Publication date
Application filed by Boehringer Ingelheim International Gmbh filed Critical Boehringer Ingelheim International Gmbh
Priority claimed from PCT/EP2017/064007 external-priority patent/WO2017211979A1/en
Publication of NZ747331A publication Critical patent/NZ747331A/en
Publication of NZ747331B2 publication Critical patent/NZ747331B2/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to combinations of Linagliptin with metformin for use int he treatment of metabolic diseases in patients having chronic kidney disease (CKD).

Claims (22)

Claims:
1. Use of linagliptin or a ceutically acceptable salt thereof, for the manufacture of a medicament for ng and/or preventing type 2 es in a patient with chronic kidney disease (CKD) having estimated ular filtration rate (eGFR; mL/minute/1.73 m2) levels down to 45, or down to 30, including having eGFR of 30 to 60 mL/minute/1.73 m2 (CKD stage 3); wherein the medicament is to be administered to the patient in combination with metformin or a pharmaceutically acceptable salt thereof, and optionally one or more further active agents; wherein: the patient has chronic renal impairment having eGFR levels 45-59, mild-tomoderate stage (CKD stage 3a), and the m daily dose of metformin or pharmaceutically acceptable salt thereof to be administered to the patient is 2000 mg; or the patient has chronic renal impairment having eGFR levels 30-44, moderate-tosevere stage (CKD stage 3b), and the maximum daily dose of metformin or pharmaceutically acceptable salt thereof to be administered to the patient is 1000
2. Use of metformin, or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating and/or preventing type 2 diabetes in a patient with chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR; mL/minute/1.73 m2) levels down to 45, or down to 30, including having eGFR of 30 to 60 mL/minute/1.73 m2 (CKD stage 3); wherein the medicament is to be administered to the patient in combination with linagliptin or a pharmaceutically acceptable salt thereof, and optionally one or more further active agents; wherein: the patient has chronic renal ment having eGFR levels 45-59, mild-tomoderate stage (CKD stage 3a), and the maximum daily dose of metformin or ceutically acceptable salt thereof to be administered to the patient is 2000 mg; or the patient has chronic renal impairment having eGFR levels 30-44, moderate-tosevere stage (CKD stage 3b), and the maximum daily dose of metformin or pharmaceutically acceptable salt thereof to be administered to the patient is 1000
3. Use of iptin or a pharmaceutically acceptable salt f, for the manufacture of a ment for treating and/or ting type 2 diabetes mellitus and/or conditions related o in a type 2 diabetes patient with chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR; mL/minute/1.73 m2) levels down to 45, or down to 30, including having eGFR of 30 to 60 mL/minute/1.73 m2 (CKD stage 3); wherein the medicament is to be administered to the patient in combination with metformin or a pharmaceutically acceptable salt thereof, and optionally one or more further active agents; wherein: the patient has chronic renal impairment having eGFR levels 45-59, mild-tomoderate stage (CKD stage 3a), and the maximum daily dose of metformin or pharmaceutically able salt thereof to be administered to the patient is 2000 mg; or the patient has chronic renal impairment having eGFR levels 30-44, moderate-tosevere stage (CKD stage 3b), and the m daily dose of metformin or pharmaceutically able salt thereof to be administered to the patient is 1000
4. Use of metformin or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating and/or preventing type 2 diabetes mellitus and/or conditions related thereto in a type 2 diabetes patient with c kidney disease (CKD) having estimated glomerular filtration rate (eGFR; mL/minute/1.73 m2) levels down to 45, or down to 30, including having eGFR of 30 to 60 mL/minute/1.73 m2 (CKD stage 3); wherein the medicament is to be stered to the patient in combination with linagliptin or a pharmaceutically acceptable salt thereof, and optionally one or more further active agents; wherein: the t has chronic renal impairment having eGFR levels 45-59, mild-tomoderate stage (CKD stage 3a), and the maximum daily dose of metformin or pharmaceutically acceptable salt thereof to be stered to the patient is 2000 mg; or the t has chronic renal impairment having eGFR levels 30-44, moderate-tosevere stage (CKD stage 3b), and the maximum daily dose of metformin or pharmaceutically acceptable salt thereof to be administered to the patient is 1000
5. The use of any one of claims 1 to 4, wherein the metformin or pharmaceutically acceptable salt f is in the form of metformin hloride.
6. The use of any one of claims 1 to 5, wherein said medicament is for: i) ng type 2 diabetes mellitus; ii) treating or slowing progression of chronic kidney disease (diabetic nephropathy); and/or iii) treating, preventing, protecting against, reducing the risk of, delaying the progression and/or delaying the occurrence of albuminuria (micro- or macro-albuminuria).
7. The use of any one of claims 1 to 6, wherein the linagliptin or ceutically acceptable salt thereof and metformin or pharmaceutically acceptable salt thereof are to be administered in a single pharmaceutical composition, such as e.g. in form of a single oral dosage form (e.g. tablet).
8. The use according to claim 7, wherein the linagliptin or pharmaceutically acceptable salt thereof is present in the ceutical composition in a dosage strength of 2.5 mg, preferably for twice daily oral administration; or of 5 mg, preferably for once daily oral administration.
9. The use according to claim 7 or 8, wherein the metformin or pharmaceutically acceptable salt thereof is present in the pharmaceutical composition in a dosage strength of 500 mg, 850 mg or 1000 mg, preferably in form of immediate release metformin, preferably for twice daily oral administration; or of 500 mg, 750 mg, 1000 mg, 1500 mg or 2000 mg, ably in form of extended release min, preferably for once daily oral administration.
10. The use according to claim 7, wherein the pharmaceutical composition comprises 2.5 mg linagliptin or a pharmaceutically acceptable salt thereof and 500 mg, 850 mg or 1000 mg metformin or a ceutically acceptable salt thereof, optionally in an immediate release form, and ally one or more pharmaceutically auxiliaries, such as e.g. for twice daily oral administration of the composition.
11. The use according to claim 7, wherein the pharmaceutical composition ses 5 mg linagliptin or a pharmaceutically acceptable salt thereof and 1000 mg metformin or a pharmaceutically acceptable salt thereof, optionally in an extended e form, and optionally one or more pharmaceutically auxiliaries, such as e.g. for once daily oral administration of the ition as one tablet, or wherein the pharmaceutical composition comprises 2.5 mg linagliptin or a pharmaceutically acceptable salt thereof and 750 mg or 1000 mg metformin or a pharmaceutically acceptable salt thereof, optionally in an extended release form, and ally one or more pharmaceutically auxiliaries, such as e.g. for once daily oral administration of the composition as two tablets.
12. The use ing to any one of claims 1 to 11, wherein linagliptin or a pharmaceutically acceptable salt thereof is to be administered in a total oral daily dose of 5 mg, such as e.g. 2.5 mg linagliptin twice daily or 5 mg linagliptin once daily.
13. The use ing to any one of claims 1 to 12, wherein metformin or a pharmaceutically acceptable salt thereof is to be administered up to maximum daily dose, such as e.g. up to 500 mg, 1000 mg or 2000 mg per day.
14. The use according to any one of claims 1 to 13, wherein the type 2 es patient has not been usly d with an antihyperglycemic agent; or wherein the type 2 diabetes patient has insufficient glycemic control despite previous mono-therapy with metformin; or wherein the type 2 diabetes patient has insufficient glycemic control despite previous dual combination therapy with metformin and a sulphonylurea; or wherein the type 2 diabetes patient has insufficient glycemic control despite us dual combination therapy with metformin and an insulin.
15. The use according to any one of claims 1 to 14, wherein the patient has (chronic) renal impairment of te stage (CKD stage 3, eGFR 30-60); optionally with or without micro- or macroalbuminuria, in particular with micro- or macroalbuminuria.
16. The use ing to any one of claims 1 to 15, wherein the patient has chronic renal impairment of o-moderate stage having eGFR levels 45-59 (CKD stage 3a), wherein the metformin or pharmaceutically able salt thereof is metformin hydrochloride, and wherein the maximum daily dose of metformin hydrochloride to be administered to the patient is 2000 mg.
17. The use ing to any one of claims 1 to 15, wherein the patient has chronic renal impairment of moderate-to-severe stage having eGFR levels 30-44 (CKD stage 3b), wherein the metformin or pharmaceutically acceptable salt thereof is metformin hydrochloride, and wherein the maximum daily dose of metformin hydrochloride to be administered to the patient is 1000 mg.
18. The use according to any one of claims 1 to 17, wherein the patient has: albuminuria (e.g. micro- or macro-albuminuria) previous macrovascular (e.g. cardio- or cerebrovascular) disease (such as e.g. myocardial infarction, coronary artery e, (ischemic or haemorrhagic) stroke, d artery disease and/or peripheral artery disease), and/or either (mild or moderate) renal impairment (e.g. CKD stage 1, 2 or 3, such as CKD stage 1, 2 (mild) or 3a (mild-moderate), ably eGFR = 45-75 mL/min/1.73 m2) with macroalbuminuria (moderate or severe) renal impairment (e.g. CKD stage 3, such as CKD stage 3b (moderate-severe), preferably eGFR 30-45 mL/min/1.73 m2, or CKD stage 4, preferably eGFR 15-29 mL/min/1.73 m2), with or without any albuminuria (such as e.g. with or without micro- or macro-albuminuria).
19. The use according to any one of claims 1 to 18, wherein the patient has: (i) nuria (micro or macro) (such as e.g. urine albumin creatinine ratio (UACR) = 30 mg/g creatinine or = 30 mg/l (milligram albumin per liter of urine) or = 30 µg/min (microgram albumin per minute) or = 30 mg/24 h (milligram albumin per 24 hours)) and previous macrovascular disease, such as e.g. defined as one or more of a) to f): a) previous myocardial infarction, b) advanced coronary artery disease, c) high-risk -vessel coronary artery e, d) previous ischemic or rhagic stroke, e) presence of carotid artery disease, f) presence of peripheral artery disease; and/or (ii) impaired renal function (e.g. with or without CV co-morbidities), such as e.g. defined • impaired renal function with an eGFR 15-45 mL/min/1.73 m2 or 30-45 mL/min/1.73 m2 with any urine albumin creatinine ratio (UACR), and/or • impaired renal function with an eGFR = 45-75 mL/min/1.73 m2 with an urine albumin creatinine ratio (UACR) > 200 mg/g creatinine or > 200 mg/l gram albumin per liter of urine) or > 200 µg/min (microgram albumin per minute) or > 200 mg/24 h (milligram albumin per 24 .
20. The use according to any one of claims 1 to 19, wherein the medicament is to be administered to the patient in combination with one or more active agents; n the one or more active agents are selected from: other antidiabetic agents such as an insulin or a sulfonylurea and/or antihypertensive agents such as an angiotensin-converting enzyme (ACE) tor or an angiotensin II receptor blocker (ARB).
21. The use according to any one of claims 1 to 20, wherein the patient is to be treated over a period of at least 1-6 years.
22. Use of iptin, or a pharmaceutically acceptable salt thereof, and metformin or a pharmaceutically acceptable salt thereof, optionally in the form of metformin hydrochloride, and optionally one or more further active agents, for the cture of a medicament for ng and/or preventing type 2 diabetes in a patient, wherein the patient has (chronic) renal impairment of moderate-to-severe stage such as having eGFR levels 30-44 (CKD stage 3b), wherein the maximum daily dose of metformin or a pharmaceutically acceptable salt thereof, optionally metformin hydrochloride, is 1000 mg, wherein linagliptin or a pharmaceutically able salt thereof and metformin or a pharmaceutically acceptable salt thereof are to be administered in a single pharmaceutical composition in the form of a single oral dosage form comprising 2.5 mg linagliptin or a ceutically acceptable salt thereof and 500 mg metformin or a pharmaceutically acceptable salt thereof, optionally in an immediate release form, and optionally with one or more pharmaceutically auxiliaries, which is to be administered twice daily to the patient. Boehringer Ingelheim International GmbH By the Attorneys for the Applicant N & FERGUSON
NZ747331A 2017-06-08 Combinations of linagliptin and metformin NZ747331B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP16174075 2016-06-10
EP17154248 2017-02-01
PCT/EP2017/064007 WO2017211979A1 (en) 2016-06-10 2017-06-08 Combinations of linagliptin and metformin

Publications (2)

Publication Number Publication Date
NZ747331A NZ747331A (en) 2025-06-27
NZ747331B2 true NZ747331B2 (en) 2025-09-30

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