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WO2017023361A1 - Composition pharmaceutique comprenant du sumatriptan pour le traitement de la migraine - Google Patents

Composition pharmaceutique comprenant du sumatriptan pour le traitement de la migraine Download PDF

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Publication number
WO2017023361A1
WO2017023361A1 PCT/US2016/015961 US2016015961W WO2017023361A1 WO 2017023361 A1 WO2017023361 A1 WO 2017023361A1 US 2016015961 W US2016015961 W US 2016015961W WO 2017023361 A1 WO2017023361 A1 WO 2017023361A1
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Prior art keywords
sumatriptan
composition
bmi
patient
patients
Prior art date
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PCT/US2016/015961
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English (en)
Inventor
Prabhu PRABHAKARA
Rajesh Ramesh PATIL
Piyush Gupta
Rajeev Singh Raghuvanshi
Anil N. NAMBOODIRIPAD
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Dr Reddys Laboratories Ltd
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Dr Reddys Laboratories Ltd
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Filing date
Publication date
Priority claimed from US15/011,357 external-priority patent/US10537554B2/en
Application filed by Dr Reddys Laboratories Ltd filed Critical Dr Reddys Laboratories Ltd
Priority to CN201680050798.8A priority Critical patent/CN107921023A/zh
Priority to EP16706279.3A priority patent/EP3331524A1/fr
Priority to CA2994748A priority patent/CA2994748C/fr
Priority to BR112018002433-3A priority patent/BR112018002433A2/pt
Priority to MX2018001528A priority patent/MX385725B/es
Publication of WO2017023361A1 publication Critical patent/WO2017023361A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents

Definitions

  • the present disclosure relates to compositions and methods for treating migraine or cluster headache in a human patient.
  • Migraine is a common neurological disorder that greatly affects quality of life and increases work disruption. An average of 6% and 17% of men and women, respectively, suffer from migraine headache. The cause of migraine is uncertain but may be the result of vascular and/or neurological dysfunction.
  • Sumatriptan has been approved for treatment of migraines and is available in various dosage forms, such as subcutaneous injection, oral tablets and nasal spray and marketed in different strengths (6 to 100 mg).
  • Sumatriptan is a serotonin type 1 receptor agonist that has a selective but heterogeneous effect on the carotid arterial system to relieve migraines.
  • Current theories proposed to explain the etiology of migraine headache suggest that symptoms are due to local cranial vasodilatation and/or to the release of sensory neuropeptides (including substance P and calcitonin gene -related peptide) through nerve endings in the trigeminal system.
  • the therapeutic activity of sumatriptan for the treatment of migraine is thought to be due to the agonist effects at the 5-HT IB/ID receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of proinflammatory neuropeptide release (IMITREX® Injection Labeling, October 2012).
  • IMITREX® subcutaneous injection products for the acute treatment of migraine, with or without aura are available in 4 mg/0.5 mL and 6 mg/0.5 mL concentrations as single-dose pre-filled syringes (PFSs) for use with an autoinjector pen (IMITREX® STATdose, NDA 020080), and as a single-dose vial of 6 mg/0.5 mL for SC injection (IMITREX®).
  • PFSs single-dose pre-filled syringes
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0 - 2 of about 30 ng.hr/ml to about 50 ng.hr/ml; (c) AUCo
  • the methods comprise measuring the patient's body mass index (BMI).
  • BMI body mass index
  • the subcutaneous administration results in a systemic exposure that is greater in patients with a BMI of less than about 26 compared to patients with a BMI of greater than or equal to about 26.
  • the subcutaneous administration results in a systemic exposure that is greater than that achieved by an equivalent dose of a commercially available sumatriptan in patients with a BMI of less than about 26.
  • the equivalent dose (3 mg) of the commercially available sumatriptan is half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®.
  • the subcutaneous administration results in a systemic exposure that is higher in white patients than in non-white patients. In some embodiments, the subcutaneous administration results in a C max that is greater than 50 ng/ml in patients having a BMI of less than about 26. In some embodiments, the subcutaneous administration results in an AUC 0 - 2 that is greater than 40 ng.hr/ml in patients having a BMI of less than about 26. In some embodiments, the subcutaneous administration results in an AUCo-inf that is greater than 60 ng.hr/ml in patients having a BMI of less than about 26.
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: measuring the BMI of the patient; selecting the patient having a BMI of less than about 26; subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0 - 2 of about 30 ng.h
  • the subcutaneous administration results in a systemic exposure that is greater than that achieved by an equivalent dose of a commercially available sumatriptan.
  • the equivalent dose (3 mg) of the commercially available sumatriptan is half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®.
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient, said method comprising: subcutaneously administering to the patient, at a maximum recommended frequency according to the body mass index (BMI) of the patient, a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0 - 2 of about 30 ng.hr/ml
  • the maximum recommended frequency of administration is not more than four times a day if the BMI is less than about 26. In some embodiments, the maximum recommended frequency of administration is not more than four times a day if the BMI is greater than or equal to about 26.
  • compositions for use in treating migraine or cluster headache in a patient in need thereof comprising: an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; wherein said composition is subcutaneously administered to the patient; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0 - 2 of about 30 ng.hr/ml to about 50 ng.hr/ml; (c)
  • compositions for use in treating migraine or cluster headache in a patient in need thereof comprising: an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; wherein the BMI of the patient is measured; wherein the patient having a BMI of less than about 26 is selected; wherein said composition is subcutaneously administered to the patient; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0
  • compositions for use in treating migraine or cluster headache in a patient comprising: an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00; wherein said composition has a pH of about 4.2 to 5.3; wherein said composition is subcutaneously administered to the patient at a maximum recommended frequency according to the body mass index (BMI) of the patient; and wherein the subcutaneous administration of said composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: (a) C max of about 35 ng/ml to about 57 ng/ml; (b) AUC 0 - 2 of about 30 ng.hr/m
  • sumatriptan herein refers to sumatriptan or its pharmaceutically acceptable salt.
  • the amount of sumatriptan pharmaceutically acceptable salt used in the composition as per this disclosure is equivalent to 3 mg of sumatriptan base.
  • sumatriptan succinate salt is equivalent to 3 mg of sumatriptan base.
  • migraine refers to migraine with or without aura.
  • treating migraine refers to acute treatment of migraine attacks with or without aura.
  • treating cluster headache refers to acute treatment of cluster headache episodes, with or without migraine.
  • a therapeutic agent or a protective agent may comprise a "drug.”
  • a “drug” refers to a therapeutic agent or a diagnostic agent and includes any substance, other than food, used in the prevention, diagnosis, alleviation, treatment, or cure of a disease. Stedman's Medical Dictionary, 25th Edition (1990).
  • the drug can include any substance disclosed in at least one of: The Merck Index, 12th Edition (1996); Pei-Show Juo, Concise Dictionary of Biomedicine and Molecular Biology, ( 1996); U.S. Pharmacopeia Dictionary, 2000 Edition; and Physician's Desk Reference, 2001 Edition.
  • the therapeutic agent is one of the embodiments of the compositions described herein.
  • sumatriptan compositions comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00.
  • the sumatriptan compositions have a pH of 4.2 to 5.3.
  • the compositions comprise an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the total volume of the sumatriptan compositions is about 0.5 ml.
  • the compositions comprise an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, wherein the sumatriptan compositions have a pH of 4.2 to 5.3, and wherein the total volume of the sumatriptan compositions is about 0.5 ml.
  • the compositions comprise an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for the period of at least 3 months when stored at 40 ⁇ 2°C and 75 ⁇ 5% relative humidity.
  • the compositions comprise about 0.5 ml of aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for the period of at least 3 months when stored at 40 ⁇ 2°C and 75 ⁇ 5% relative humidity.
  • the compositions comprise an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for the period of at least 12 months when stored at 30 ⁇ 2°C and 65 ⁇ 5% relative humidity.
  • the compositions comprise about 0.5 ml of aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for the period of at least 12 months when stored at 30 ⁇ 2°C and 65 ⁇ 5% relative humidity.
  • the compositions comprise an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for at least 3 months at 40°C/75 % relative humidity or for at least 12 months at 30°C/65 % relative humidity.
  • the compositions comprise about 0.5 ml of aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein said sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00, and wherein the sumatriptan compositions have a pH of 4.2 to 5.3 and are stable for at least 3 months at 40°C/75 % relative humidity or for at least 12 months at 30°C/65 % relative humidity.
  • the sumatriptan solution may be formulated in a variety of compositions, for example, as a sterile injectable composition.
  • a sterile injectable composition such as a sterile injectable aqueous or oleaginous suspension, may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent.
  • the acceptable vehicles and solvents include mannitol, water, Ringer's solution and isotonic sodium chloride solution.
  • Suitable carriers and other pharmaceutical composition components are typically sterile.
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the sumatriptan composition may be adjusted to have a pH that is suitable for subcutaneous administration, such as a pH of about 4.2 to 5.3.
  • a pH that is suitable for subcutaneous administration such as a pH of about 4.2 to 5.3.
  • the aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof and sodium chloride may be present in the composition in any suitable ratios, for example, from about 0.80: 1.00 to about 1.40: 1.00.
  • sumatriptan subcutaneous injection could be 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX® by GlaxoSmithKline or its generic versions.
  • Commercially available sumatriptan subcutaneous injection may also include 4 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX® STATdose by GlaxoSmithKline or its generic versions.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure that is equivalent to or greater than that achieved by an equivalent dose (3 mg) of a commercially available sumatriptan in patients, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo- i nf , that is equivalent to or greater than that achieved by an equivalent dose of a commercially available sumatriptan in patients.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC o-t, AUCo-2 or AUCo-inf, that is higher than that achieved by an equivalent dose of a commercially available sumatriptan in patients.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo-inf, that is about the same of that achieved by a higher dose, e.g., 4 mg, of a commercially available sumatriptan in patients.
  • a method of treating migraine or cluster headache in a patient in need thereof includes subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of the solution between 275 to 315 mOsm/kg.
  • the sumatriptan and sodium chloride are present in a ratio of from about 0.80: 1.00 to about 1.40: 1.00.
  • the composition has a pH of about 4.2 to 5.3.
  • Subcutaneous administration of the composition to the patient results in a systemic exposure characterized by at least one of the following plasma profiles: C max of about 35 ng/ml to about 57 ng/ml; AUC 0 - 2 of about 30 ng.hr/ml to about 50 ng.hr/ml; AUCo- t of about 41 ng.hr/ml to about 68 ng.hr/ml; and AUCo-inf of about 43 ng.hr/ml to about 70 ng.hr/ml.
  • the subcutaneous administration of said composition to the patient results in a systemic exposure that is at 90% Confidence Interval (CI) of the relative mean of C max , AUC 0 -t, AUC o-inf and AUC0-2 within 80.00% to 125.00% of 0.25 ml of commercially available 6 mg/0.5ml sumatriptan subcutaneous injection.
  • CI Confidence Interval
  • the subcutaneous administration of the sumatriptan composition may result in a systemic exposure that is significantly higher in certain patients than in other patients.
  • the subcutaneous administration results in a systemic exposure that is significantly higher in white patients than in non-white patients.
  • BMI Body Mass Index
  • the presently disclosed methods result in systemic exposures that correlate to the BMI of the patients being treated.
  • the subcutaneous administration of the sumatriptan composition results in a systemic exposure that is greater in patients with a lower BMI compared to patients with a higher BMI.
  • the subcutaneous administration results in a systemic exposure that is greater in patients with a BMI of less than about 26 compared to patients with a BMI of greater than or equal to about 26.
  • the difference between the systemic exposure of patients with a BMI of less than about 26 and a systemic exposure of patients with a BMI of greater than or equal to about 26 may be statistically significant.
  • the methods disclosed herein may comprise measuring the patient's BMI.
  • the BMI is defined as the body mass divided by the square of the body height, and is universally expressed in units of kg/m , resulting from mass in kilograms and height in meters.
  • the correlation between the systemic exposure and the BMI of the patient may be used in a variety of ways to optimize the effectiveness and/or minimize the side effects of the sumatriptan composition disclosed herein.
  • the BMI of the patients may be used to select patients that will achieve a higher systemic exposure, and therefore more effectiveness using the sumatriptan composition disclosed herein.
  • the BMI of the patients may also be used to select patients that will achieve similar effectiveness using the 3 mg sumatriptan composition disclosed herein as using the higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan, and therefore fewer side effects.
  • the BMI of the patients may be used to calculate the maximum recommended frequency of administration of the sumatriptan composition disclosed herein.
  • patients with a higher BMI will be given a higher maximum recommended frequency of administration in comparison to patients with a lower BMI.
  • some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: measuring the BMI of the patient; selecting the patient having a BMI of less than about 26; subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure that is equivalent to or greater than that achieved by an equivalent dose (3 mg) of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of less than about 26.
  • an equivalent dose (3 mg) of a commercially available sumatriptan e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of less than about 26.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC o-t, AUCo-2 or AUCo-inf, that is equivalent to or greater than that achieved by an equivalent dose of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of less than about 26.
  • a systemic exposure e.g., C max , AUC o-t, AUCo-2 or AUCo-inf
  • a commercially available sumatriptan e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of less than about 26.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC o-t; AUCo-2 or AUCo-inf, that is higher than that achieved by an equivalent dose of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of less than about 26.
  • a systemic exposure e.g., C max , AUC o-t; AUCo-2 or AUCo-inf
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure in patients with a BMI of less than about 26, e.g., Cmax, AUC o-t, AUC0-2 or AUCo-inf, that is about the same of that achieved by a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan in patients with a BMI of greater than or equal to about 26.
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: measuring the BMI of the patient; selecting the patient having a BMI of greater than or equal to about 26; subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure that is equivalent to or greater than that achieved by an equivalent dose (3 mg) of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of greater than or equal to about 26.
  • an equivalent dose 3 mg
  • a commercially available sumatriptan e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo-inf, that is equivalent to or greater than that achieved by an equivalent dose of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of greater than or equal to about 26.
  • a systemic exposure e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo-inf
  • a commercially available sumatriptan e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of greater than or equal to about 26.
  • the subcutaneous administration of the sumatriptan composition as disclosed herein may result in a systemic exposure, e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo-inf, that is higher than that achieved by an equivalent dose of a commercially available sumatriptan, e.g., half of a 6 mg sumatriptan subcutaneous injection sold under the brand name of IMITREX®, in patients with a BMI of greater than or equal to about 26.
  • a systemic exposure e.g., C max , AUC 0-t , AUC 0 - 2 or AUCo-inf
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: subcutaneously administering to the patient a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg; wherein incidences of side effects are reduced at least 10% compared with commercially available sumatriptan subcutaneous injection.
  • the generally observed adverse or side effects of sumatriptan can be categorized as atypical sensations which includes tingling, warm or hot sensation, feeling of heaviness, burning sensation, numbness, feeling strange, tight feeling in head; cardiovascular adverse effect such as which includes discomfort in throat, nasal cavity/sinuses, flushing, chest discomfort, tightness in chest, pressure in chest, ear, nose, and throat; musculoskeletal adverse effect such as weakness, Neck pain/stiffness myalgia; neurological adverse effect such as dizziness or vertigo, drowsiness or sedation; miscellaneous adverse effects such as jaw discomfort and sweating.
  • the incidence of side effects may be directly or indirectly associated with the systemic exposure in a patient. Therefore, to reduce the incidence of side effects, it may be desirable to lower the systemic exposure in comparison to a commercially available sumatriptan.
  • the methods disclosed herein may result in a lower systemic exposure in patients in comparison to patients treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan.
  • the methods disclosed herein may result in a systemic exposure that is 10%, 20%, 30%, 40%, 50% lower in patients in comparison to patients treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan.
  • the methods disclosed herein may also be used to reduce the incidence of side effects by lowering the systemic exposure in patients with low or high BMI in comparison to patients treated with a commercially available sumatriptan.
  • the methods disclosed herein may result in a systemic exposure that is 10%, 20%, 30%, 40%, 50% lower in patients with a BMI of less than about 26 in comparison to patients with a BMI of less than about 26 treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan.
  • the methods disclosed herein may result in a systemic exposure that is 10%, 20%, 30%, 40%, 50% lower in patients with a BMI of greater than or equal to about 26 in comparison to patients treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan with a BMI of greater than or equal to about 26.
  • the methods disclosed herein may result in a systemic exposure that is 10%, 20%, 30%, 40%, 50% lower in patients with a BMI of greater than or equal to about 26 in comparison to patients treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan with a BMI of less than about 26.
  • the methods disclosed herein may result in a systemic exposure that is 10%, 20%, 30%, 40%, 50% lower in patients with a BMI of less than about 26 in comparison to patients treated with a higher dose, e.g., 4 mg or 6 mg, of a commercially available sumatriptan with a BMI of greater than or equal to about 26.
  • Some embodiments disclosed herein provide methods of treating migraine or cluster headache in a patient in need thereof, said method comprising: subcutaneously administering to the patient, at a maximum recommended frequency according to the body mass index (BMI) of the patient, a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the maximum recommended frequency of administration is not more than four times a day if the BMI is less than about 26. In some embodiments, the maximum recommended frequency of administration is not more than four times a day if the BMI is greater than or equal to about 26.
  • Some embodiments disclosed herein provide methods for treating medication overuse headache or rapid escalating migraine in a patient in need thereof, said method comprising: subcutaneously administering subcutaneously administering a composition comprising an aqueous solution of sumatriptan or its pharmaceutically acceptable salts thereof in an amount equivalent to 3 mg of sumatriptan base, and sodium chloride in an amount to maintain the osmolality of said solution between 275 to 315 mOsm/kg.
  • the methods do not require detoxification of patients including withdrawal of the overused drugs.
  • compositions comprising an aqueous solution of present application is manufactured by a two- step process comprising the steps of:
  • step a adding required quantity of sumatriptan or its pharmaceutically acceptable salts thereof in the solution of step a, and making the final volume up to 100% (of batch size) using water for injection; wherein the process steps being performed in said order to maintain the osmolality of said solution between 275 to 315 mOsm/kg and increases solubility of sumatriptan by at least 9 percent.
  • the composition disclosed herein may be sterilized by filtration. Terminal sterilization may cause instability and increase in impurities in the compositions disclosed herein.
  • compositions disclosed herein may be manufactured in light controlled conditions. U.V. and visible light may cause instability and increase in impurities in the compositions disclosed herein.
  • compositions disclosed herein can be dispensed by suitable device such autoinjector devices, prefilled syringes, ampoules, vials, a glass vial, a plastic vial etc.
  • compositions disclosed herein can be dispensed by pre-filled syringe fully assembled into an auto-injector device.
  • compositions disclosed herein can be dispensed in disposable, single-use auto-injector containing about 0.5 mL of sumatriptan succinate in an amount equivalent to 3.0 mg of sumatriptan base in a pre-filled syringe (PFS) fully assembled for ready use.
  • PFS pre-filled syringe
  • the compositions disclosed herein can be dispensed in suitable devices that are suitable for containment and administration. Further, the devices are packed in suitable secondary package a material that envelops the devices.
  • the secondary packaging provides additional barriers to elements that can degrade the composition such as light and oxygen.
  • Some devices may also be designed to permeable to oxygen and other gases. For example, syringes, cartridges and the like can have permeable parts to allow sterilization process with, for example, ethylene oxide.
  • the compositions disclosed herein comprise a secondary packaging in addition to the dispensed devices.
  • Secondary packaging includes any container that receives the device (e.g., a box, bag, blister, canister, bottle and the like) and is sealed to prevent ingress of oxygen.
  • the secondary packaging is made from material that has very low permeability to oxygen molecules (e.g., ethylene vinyl alcohol, aluminum, glass, polyamide and the like).
  • the secondary packaging further comprises an oxygen absorber inside.
  • the oxygen absorber functions to absorb any oxygen present in the secondary packaging. Suitable materials for oxygen absorbers include iron, low molecular weight organic compounds such as ascorbic acid and sodium ascorbate and polymeric materials incorporating a resin and a catalyst. Oxygen absorbers are contemplated to be in any size or shape including sachet, pouch, canister, lining, sticker, etc. as well as part of the secondary packaging or primary packaging container itself.
  • Example 3 Assessment of the stability of the composition of Example 1
  • a tmax is presented as median (minimum, maximum)
  • Example 4 The effect of age, BMI, and race on plasma concentrations of subcutaneous sumatriptan: a pooled analysis
  • SC sumatriptan is approved by the Food and Drug Administration (FDA) and are marketed in the United States.
  • FDA Food and Drug Administration
  • SC sumatriptan has a better efficacy profile than oral and IN sumatriptan products. Absorption is more rapid with SC administration (time to reach maximum observed [peak] plasma concentration [T max ] for SC Imitrex® is 12 minutes (5-20 minutes), significantly shorter than that for the oral (2 to 2.5 hours) and nasal routes (60-90 minutes). As a result, onset of action with SC sumatriptan (10 minutes) is faster than with IN (30 to 45 minutes) or oral (45 to 60 minutes) delivery.
  • PK pharmacokinetic
  • Example 1 Currently SC sumatriptan is available in the U.S. in 4 and 6 mg dosage forms (Imitrex® STATdose, 0.5 ml) injections and as an injectable solution (Imitrex® injection, 3 mg / 0.25 ml).
  • the composition of Example 1 has been made for SC injection in a single-dose, 0.5-mL prefilled syringe as a ready-to-use disposable autoinjector.
  • Two clinical pharmacology studies were conducted to support the PK bridge between Example 1 and Imitrex®.
  • the efficacy profile of Example 1 is expected to be the same as existing 3-mg sumatriptan injection products (half of the 6 mg Imitrex ® dosage form).
  • Study 002 (CD-002): This 3 -way crossover study compared Example 1 to Imitrex® injection 3 mg and 6 mg. Subjects were randomized to one of the six treatment sequences.
  • Study 003 (CD-003): This 3-way crossover study compared Example 1 to Imitrex® 4 mg STATdose system and 6 mg STATdose system. Subjects were randomized to one of the six treatment sequences.
  • Plasma concentrations (Cp) of sumatriptan were determined using techniques known in the art. Pharmacokinetic parameters for each dosing session were determined using non-compartmental methods with WinNonlin Version 6.3 (Certara, Cary, NC) or SAS Version 9.3 (SAS Institute, Cary, NC). The following parameters were determined:
  • AUC 0 - 2 Area under the Cp vs. time curve from the time of drug administration to the 2-hour sample.
  • AUCo-inf Area under the concentration-time curve from the time of drug administration extrapolated to infinity. AUCo-inf is calculated as the sum of AUCo- t (where t is last measured non-zero concentration) plus the ratio of the last measurable Cp to the elimination rate constant. AUC was calculated by the linear trapezoidal method.
  • AUCo-inf for stockier subjects was 0.87 - 0.97 times the value for leaner subjects. For leaner subjects receiving Example 1 , AUCo-inf was less than that for stockier subjects receiving 4 mg Imitrex® and larger than that for stockier subjects receiving 3 mg Imitrex®. C max for stockier subjects was 0.88 - 0.98 times the value for leaner subjects. For leaner subjects receiving Example 1, C max was less than that for stockier subjects receiving 4 mg Imitrex® and larger than that for stockier subjects receiving 3 mg Imitrex®.
  • White subjects differ (P ⁇ 0.05) from non-white subjects by t test.
  • BMI the value of the BMI was used to divide subjects into two groups; then the value for each metric was compared between these groups. If the ratio were markedly less than unity, it would suggest that subjects with higher BMI experienced lower exposure for that metric. In turn, it might imply different dosing requirements as a function of that metric. For C max and AUC 0 - 2 (the two metrics that are probably most relevant to sumatriptan's efficacy), these ratio values for weight and BMI were > 0.75 for all products.

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Abstract

La présente invention concerne un procédé de traitement de la migraine ou de l'algie vasculaire de la face chez un patient humain, ledit procédé consistant à administrer par voie sous-cutanée une composition comprenant du sumatriptan ou son sel pharmaceutiquement acceptable, dans une quantité équivalente à 3 mg de base de sumatriptan.
PCT/US2016/015961 2015-08-05 2016-02-01 Composition pharmaceutique comprenant du sumatriptan pour le traitement de la migraine Ceased WO2017023361A1 (fr)

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CN201680050798.8A CN107921023A (zh) 2015-08-05 2016-02-01 用于治疗偏头痛的包含舒马曲坦的药物组合物
EP16706279.3A EP3331524A1 (fr) 2015-08-05 2016-02-01 Composition pharmaceutique comprenant du sumatriptan pour le traitement de la migraine
CA2994748A CA2994748C (fr) 2015-08-05 2016-02-01 Composition pharmaceutique comprenant du sumatriptan pour le traitement de la migraine
BR112018002433-3A BR112018002433A2 (pt) 2015-08-05 2016-02-01 composição farmacêutica para tratamento da enxaqueca
MX2018001528A MX385725B (es) 2015-08-05 2016-02-01 Composición farmacéutica que comprende sumatriptán para tratamiento de migraña.

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US15/011,357 US10537554B2 (en) 2015-08-05 2016-01-29 Pharmaceutical composition for treating migraine
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11364225B2 (en) 2019-08-21 2022-06-21 Bn Intellectual Properties, Inc. Pharmaceutical formulation for treating symptoms of migraine and cluster headaches, and method of using the same

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
"Physician's Desk Reference", 2001, .
"U.S. Pharmacopeia Dictionary", 2000, .
ANONYMOUS: "IMITREX (sumatriptan succinate) Injection", January 2006 (2006-01-01), internet, pages 1 - 25, XP055267215, Retrieved from the Internet <URL:http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020080s036lbl.pdf> [retrieved on 20160420] *
ANONYMOUS: "Sumavel DosePro (sumatriptan injection), for subcutaneous use", January 2014 (2014-01-01), internet, pages 1 - 8, XP055267185, Retrieved from the Internet <URL:http://www.sumaveldosepro.com/pdf/pi.pdf> [retrieved on 20160420] *
BURKE-RAMIREZ P ET AL: "Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a comparison between ethnic groups.", HEADACHE OCT 2001, vol. 41, no. 9, October 2001 (2001-10-01), pages 873 - 882, XP002756964, ISSN: 0017-8748 *
GREGOR NORA ET AL: "Treatment of cluster headache attacks with less than 6 mg subcutaneous sumatriptan.", HEADACHE SEP 2005, vol. 45, no. 8, September 2005 (2005-09-01), pages 1069 - 1072, XP002756962, ISSN: 0017-8748 *
LANDY STEPHEN H ET AL: "Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan.", HEADACHE APR 2005, vol. 45, no. 4, April 2005 (2005-04-01), pages 346 - 349, XP002756961, ISSN: 0017-8748 *
MERCK: "The Merck Index, 12th Edition", 1996
PEI-SHOW JUO: "Concise Dictionary of Biomedicine and Molecular Biology", 1996
STEDMAN: "Stedman's Medical Dictionary, 25th Edition", 1990
VISSER W H ET AL: "Sumatriptan-nonresponders: a survey in 366 migraine patients.", September 1996, HEADACHE SEP 1996, VOL. 36, NR. 8, PAGE(S) 471 - 475, ISSN: 0017-8748, XP002756963 *
VISSER W H ET AL: "Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group.", CEPHALALGIA : AN INTERNATIONAL JOURNAL OF HEADACHE OCT 1992, vol. 12, no. 5, October 1992 (1992-10-01), pages 308 - 313, XP009189707, ISSN: 0333-1024 *
WATANABE Y ET AL: "Monitoring cortical hemodynamic changes after sumatriptan injection during migraine attack by near-infrared spectroscopy", NEUROSCIENCE RESEARCH, ELSEVIER, SHANNON, IR, vol. 69, no. 1, January 2011 (2011-01-01), pages 60 - 66, XP027544577, ISSN: 0168-0102, [retrieved on 20100925] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11364225B2 (en) 2019-08-21 2022-06-21 Bn Intellectual Properties, Inc. Pharmaceutical formulation for treating symptoms of migraine and cluster headaches, and method of using the same

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