KR-20260065892-A - Composition containing articaprant for use in the treatment of major depressive disorder

Abstract

The present disclosure relates to a method for treating major depressive disorder in a human patient, wherein the human patient has previously shown an inadequate response to other antidepressant therapy and weighs less than about 55 kg. Such a method comprises administering about 5 mg of articaprand to the human, comprising an oral composition in tablet form.

Inventors

• 돈느, 안-가엘
• 고얄, 나빈쿠마르 수바시
• 라기셰티, 차크라다르
• 리, 시아

Assignees

• 얀센 파마슈티칼즈, 인코포레이티드

Dates

Publication Date

20260511

Application Date

20240905

Priority Date

20230906

Claims (20)

1. A method for treating major depressive disorder in a human patient, comprising the step of administering a pharmaceutical composition containing about 5 mg of articaprand to a human patient, wherein the human patient has previously shown an inadequate response to other antidepressant therapy and the human patient has a body weight of about 55 kg or less.
2. In paragraph 1, the pharmaceutical composition is a tablet, method.
3. In paragraph 1 or 2, the method in which the human patient is under the age of 18.
4. A method according to any one of paragraphs 1 to 3, wherein the pharmaceutical composition is administered to a human patient once a day.
5. A method according to any one of paragraphs 1 to 4, wherein the other antidepressant therapy included one or more antidepressants.
6. In paragraph 5, the method wherein one or more antidepressants of the other antidepressant therapy included an SSRI, an SNRI, or a combination thereof.
7. A method in which, in any one of paragraphs 1 to 6, articaprand is S-articaprand.
8. A method according to any one of paragraphs 1 to 7, wherein the articaprand is crystalline articaprand.
9. A method comprising, in any one of claims 1 to 8, further comprising treatment using an effective amount of one or more antidepressants.
10. In paragraph 9, a method wherein one or more antidepressants are SSRIs, SNRIs, or combinations thereof.
11. A method in which, in any one of paragraphs 1 to 10, the patient has anhedonia.
12. A method according to any one of claims 1 to 11, wherein the pharmaceutical composition further comprises one or more of a filler, a disintegrant, a lubricant, a lubricant, a binder, and a coloring agent.
13. In paragraph 12, the filler is microcrystalline cellulose, lactose monohydrate, or silicified microcrystalline cellulose; the disintegrant is sodium croscarmellose; the lubricant is anhydrous colloidal silica; and the lubricant is magnesium stearate, method.
14. A method according to any one of claims 1 to 13, wherein the pharmaceutical composition comprises about 4% by weight to about 6% by weight of articaprand.
15. A method according to any one of claims 1 to 14, wherein the pharmaceutical composition comprises about 5 weight percent of articaprand.
16. A method according to any one of claims 1 to 15, wherein the pharmaceutical composition further comprises about 10% by weight to 99.9% by weight of a filler.
17. A method according to any one of paragraphs 1 to 16, wherein the human patient has a body weight of 52 kg or less.
18. A method according to any one of paragraphs 1 to 17, wherein the human patient has a body weight of less than 45 kg.
19. A pharmaceutical composition for use in the treatment of major depressive disorder, comprising about 5 mg of aticaprante, formulated for administration to human patients, wherein the human patient has previously shown an insufficient response to other antidepressant therapies and the human patient has a body weight of less than about 55 kg.
20. In paragraph 19, a pharmaceutical composition that is a tablet.

Description

Composition containing articaprant for use in the treatment of major depressive disorder Cross-reference regarding related applications This application claims the benefit of priority of U.S. provisional application No. 63/580,940 filed on September 6, 2023, the disclosures of which are incorporated herein by reference. Technology field The present disclosure relates to a method for treating major depressive disorder in a specific patient population by administering articaprand, comprising an oral composition of articaprand in tablet form. Kappa opioid receptors (KOR) and their intrinsic ligand, dynorphin, are localized to brain regions that influence reward and stress and may play a significant role in mood, stress, and addictive disorders. Chronic stress, drug abuse, and acute withdrawal lead to increased dynorphin expression, which activates KOR and subsequent downstream signaling pathways to suppress mesolimbic dopamine surges, thereby contributing to negative emotional states. The behavioral pharmacology of KOR antagonism has been tested in animal models of anhedonia, depression, and anxiety, indicating that there are significant effects capable of producing therapeutic benefits in humans. KOR antagonists may be effective in treating patients with mood disorders by modulating negative emotional states associated with stress responses. Only about 50% of patients with MDD demonstrate a meaningful response (an improvement of >50% compared to first-line antidepressant treatment), leaving many patients with substantially persistent disability. Treatment strategies such as antidepressant switching and adjuvant therapy can improve response, but nearly 40% of patients retain symptoms and do not achieve complete remission. Furthermore, certain patient groups, including adolescents, require different treatment options than the adult population. Based on safety and efficacy data, a 10 mg QD dose of aticaprant was selected for adult patients in specific studies; however, appropriate doses are required for adolescents (e.g., patients aged 12 to under 18) and/or patients below a certain body weight, as the proposed adult dosing regimen results in systemic exposure similar to that achieved in adults. In some embodiments, the present disclosure provides a method for treating major depressive disorder in human patients, said method comprising the step of administering a pharmaceutical composition comprising about 5 mg of articaprante to a human patient, wherein the human patient has previously shown an inadequate response to other antidepressant therapy and the human patient weighs less than about 55 kg. Such patient population typically includes adolescents aged 12 years or older and under 18 years. In another embodiment, the present disclosure provides an oral tablet comprising about 5 mg of articaprand, the oral tablet comprising about 100 mg of a core tablet, the core tablet comprising an inner granular phase and an outer granular phase, the inner granular phase comprising about 30 mg of microcrystalline cellulose, about 30 mg of lactose monohydrate, about 2.5 mg of croscarmellose sodium, and about 0.5 mg of anhydrous colloidal silica; and the outer granular phase comprising about 28.5 mg of silicified microcrystalline cellulose, about 2.5 mg of croscarmellose sodium, about 0.5 mg of anhydrous colloidal silica, and about 0.5 mg of magnesium stearate. In a further aspect, the present disclosure provides a method for treating major depressive disorder (MDD) in a human patient, comprising the step of administering the pharmaceutical composition, oral tablet, or solid pharmaceutical composition described herein to a patient. FIG. 1 is a flowchart of the manufacturing process of a tablet containing articaprand. In this figure, a refers to fine, i.e., ground articaprand. Figure 2 is a schematic diagram for the development of an adult population pharmacokinetics model. Figure 3 is a schematic workflow diagram for simulating articaprand exposure in adult and adolescent groups. Figure 4 is a graph showing the concordance of articaprant exposure in adolescent and adult groups. Left figure: The 90% predicted interval (shaded area) of the simulated articaprant steady-state AUC (0-24h) in adolescents as a function of body weight (top left) and age (bottom left) is compared with the simulated median exposure value (dashed line) and the 5th and 95th percentiles (dotted line) in adults for Scenario 5 (articaprant 5 mg QD for less than 45 kg and 10 mg QD for 45 kg or more). Right figure: The proportion of adolescents within the 5th and 95th percentiles of the simulated steady-state AUC (0-24h) in adults as a function of body weight (top right) and age (bottom right) for five different dosing plan scenarios. Figure 5 is a graph showing the weight distribution of adolescents and the proportion P of adolescents aged 12 to under 18 who weigh less than 45 kg (green) and less than 50 kg (red), respectively. All individual features mentio