Methods of treating spinal cerebellar ataxia

Abstract

There is provided a method for treating spinal cerebellar ataxia genotype 3 in a patient in need thereof, comprising administering to the patient a dosage form comprising an effective amount of triluzole hydrochloride monohydrate. Also provided is a dosage form comprising a triluzole hydrochloride monohydrate in an amount effective to treat spinal cerebellar ataxia genotype 3 in a patient in need thereof.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 63 / 344,917 filed on May 23, 2023, and all benefits arising therefrom, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention relates to a method for treating spinocerebellar ataxia. In particular, the present application relates to a method for treating spinocerebellar ataxia genotype 3. Background Art

[0004] Ataxia is a central nervous system disorder in which the patient is unable to coordinate muscles to perform voluntary movements, see, e.g., Klockgether, T. "Ataxias" in Parkinsonism and Related Disorders 13, S391-S394, 2007. Typical symptoms of ataxia are gait dysfunction, imbalance, impaired limb coordination, and speech changes. In many ataxia disorders, ataxia is attributed to degeneration of the cerebellar cortex and its afferent or efferent fiber connections. Typical brain regions affected are the cerebellum, posterior columns, pyramidal tracts, and basal ganglia. Ataxia may result in decreased motor neuron function.

[0005] Spinocerebellar ataxias ("SCA") are a group of inherited brain disorders that affect the cerebellum, a part of the brain that is critical for coordinating body movements, and sometimes the spinal cord. Spinocerebellar ataxias can be classified as ataxias associated with translated GAG repeat expansions (SCA types 1, 2, 3, 6, 7, and 17), ataxias associated with untranslated repeat expansions in noncoding regions (SCA types 10 and 12), and ataxias associated with point mutations (SCA types 5, 13, 14, and 27).

[0006] The most common SCAs include types 1, 2, 3, 6, 7, 8, and 10. SCA1 often causes gait ataxia, limb ataxia, and dysarthria, with brainstem involvement but rarely cognitive abnormalities. SCA2 is notable for the association of ataxia and dysarthria with slow saccadic eye movements and polyneuropathy. SCA3 (also known as Machado-Joseph disease) is often associated with eyelid retraction, decreased blinking, extraocular muscle palsies, dysarthria, dysphagia, and sometimes parkinsonism or peripheral neuropathy. SCA6 is less severe, usually progresses more slowly, has more limited cerebellar involvement than other SCAs, and has a later age of onset. SCA7 is characterized by retinal degeneration leading to blindness in addition to ataxia. Overall, there is significant symptom overlap between these SCAs. The common symptom presentation of the SCAs may reflect a common pathology affecting the cerebellar Purkinje cell fibers.

[0007] Currently, there are no drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of SCA. There remains a need for effective medications to treat the various types of SCA and the broader spinocerebellar ataxia population. Summary of the invention

[0008] The present invention relates to methods of treating spinocerebellar ataxia genotype 3 and dosage forms for such treatment.

[0009] In one embodiment, a method for treating spinocerebellar ataxia genotype 3 in a patient in need thereof is provided, comprising administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate.

[0010] In another embodiment, a dosage form is provided comprising an amount of troriluzole hydrochloride monohydrate effective for treating spinocerebellar ataxia genotype 3 in a patient in need thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] These and / or other aspects will become apparent and more readily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0012] Figure 1 is a graph showing the f-SARA change from randomization baseline to Week 48 in f-SARA total score by treatment arm in all SCA patients (nominal p=0.76);

[0013] Figure 2 Figure 2 is a graph showing the f-SARA change from randomization baseline to Week 48 in f-SARA total score by treatment arm in SCA3 patients (including baseline f-SARA gait item score as a covariate, nominal p=0.53);

[0014] Figure 3 a graph showing the f-SARA change from randomization baseline to Week 48 in f-SARA total score by treatment arm in SCA3 patients who were able to walk without assistance at baseline (nominal p=0.031); and

[0015] Figure 4 Table showing the frequency of falls, a treatment-emergent adverse event (TEAE), in various patient groups. DETAILED DESCRIPTION

[0016] The following detailed description is provided to help those skilled in the art to practice the present invention. Exemplary embodiments will be described in detail below. However, these embodiments are merely exemplary, and the present disclosure is not limited thereto, but is limited by the scope of the appended claims. Those of ordinary skill in the art may modify and change the embodiments described herein without departing from the spirit or scope of the present disclosure.

[0017] Therefore, the embodiments are described below only by reference to structures and schemes to explain various aspects of the specification. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. The term "or" means "and / or". Expressions such as "at least one of", when following a list of elements, modify the entire list of elements without modifying the individual elements of the list.

[0018] It should be understood that when an element is referred to as being "on" another element, it can be in direct contact with the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being "directly on" another element, there are no intervening elements.

[0019] It should be understood that although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Therefore, the first element, component, region, layer or section discussed below may be referred to as the second element, component, region, layer or section without departing from the teachings of the embodiments of the present invention.

[0020] It should be understood that the terms “comprises and / or comprising” or “includes and / or including” when used in the present specification specify the presence of stated features, regions, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components and / or groups thereof.

[0021] Unless otherwise defined, all technical and scientific terms used herein will have the same meaning as those generally understood by those of ordinary skill in the art to which the present disclosure belongs. The terms used in the description are only used to describe specific embodiments and are not intended to be restrictive. It should also be understood that terms (such as those defined in common dictionaries) should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology and the present disclosure, and unless clearly defined in this article, should not be interpreted in an idealized or overly formal sense.

[0022] As used in this application, unless otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application. Where a term is not expressly defined herein, the term is given its art-recognized meaning by a person of ordinary skill in the art applying the term in the context of its use to describe the present invention.

[0023] The articles "a" and "an" refer to one or to more than one (ie, to at least one) of the grammatical object of the article, unless the context clearly indicates otherwise. For example, "an element" means one element or more than one element.

[0024] Additional aspects will be set forth in part in the description which follows and, in part, will be apparent from the description.

[0025] The starting materials that can be used to make the pharmaceutical compositions of the present invention are readily commercially available or can be prepared by those skilled in the art.

[0026] In one embodiment, a method for treating spinocerebellar ataxia genotype 3 in a patient in need thereof is provided, comprising administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate.

[0027] In one aspect, the dosage form can be in the form of a capsule. In another aspect, the dosage form can be in the form of a tablet. The tablet can be an orally disintegrating tablet.

[0028] Troliluzole hydrochloride monohydrate is a member of the benzothiazole chemical class and is a tripeptide prodrug conjugate of riluzole. Troliluzole hydrochloride monohydrate is chemically described as 2-amino-N-({methyl-[(6-trifluoromethoxy-benzothiazol-2-ylcarbamoyl)-methyl]-carbamoyl}-methyl)-acetamide monohydrate monohydrochloride and has the structural formula:

[0029]

[0030] The molecular formula of troriluzole hydrochloride monohydrate is C 15 H 16F3N5O4S·HCl·H2O, molecular weight 473.85 g / mol (anhydrous free base form molecular weight 419.40 g / mol). The drug substance is readily soluble in water.

[0031] In one aspect, the dosage form may contain 200 mg of troriluzole hydrochloride monohydrate and may be administered to a patient daily (QD). In another aspect, the dosage form may contain 100 mg of troriluzole hydrochloride monohydrate and may be administered to a patient twice a day (BID).

[0032] In one aspect, the dosage form can be administered daily for at least forty-eight weeks. For example, the dosage form can be administered daily for forty-eight weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for forty-eight weeks, the patient can show a least squares [LS] mean change difference of -0.55 at week 48 compared to placebo (nominal p-value=0.053, 95% CI: -1.12, 0.01). When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient who was able to walk without assistance at baseline for forty-eight weeks, the patient can show a least squares [LS] mean change difference of -0.71 at week 48 compared to placebo (nominal p-value=0.031, 95% CI: -1.36, -0.07).

[0033] In another aspect, the dosage form can be administered daily for at least four weeks. For example, the dosage form can be administered daily for four weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for four weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.46 at week 4 compared to placebo. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient who was able to walk without assistance at baseline for four weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.67 at week 4 compared to placebo.

[0034] In another aspect, the dosage form can be administered daily for at least eight weeks. For example, the dosage form can be administered daily for eight weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for eight weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.12 at week 8 compared to placebo. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for eight weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.33 at week 8 compared to placebo.

[0035] In another aspect, the dosage form can be administered daily for at least twelve weeks. For example, the dosage form can be administered daily for twelve weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for twelve weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.46 at week 12 compared to placebo. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for twelve weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.71 at week 12 compared to placebo.

[0036] In another aspect, the dosage form can be administered daily for at least twenty-four weeks. For example, the dosage form can be administered daily for twenty-four weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for twenty-four weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.17 at week 24 compared to placebo. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for twenty-four weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.40 at week 24 compared to placebo.

[0037] In another aspect, the dosage form can be administered daily for at least thirty-six weeks. For example, the dosage form can be administered daily for thirty-six weeks. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for thirty-six weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.72 at week 36 compared to placebo. When a dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient for thirty-six weeks, the patient can exhibit a least squares [LS] mean difference in change of at least -0.55 at week 36 compared to placebo.

[0038] In another aspect, the dosage form can be administered daily for forty-eight weeks, and then again daily for an additional forty-eight weeks.

[0039] In another embodiment, a dosage form is provided comprising an amount of troriluzole hydrochloride monohydrate effective for treating spinocerebellar ataxia genotype 3 in a patient in need thereof. In one aspect, the dosage form may comprise troriluzole hydrochloride monohydrate in an amount of 100 mg or greater. In another aspect, the dosage form may comprise troriluzole hydrochloride monohydrate in an amount of 140 mg or greater. In yet another aspect, the dosage form may comprise troriluzole hydrochloride monohydrate in an amount of 200 mg or greater.

[0040] The present invention is further illustrated by the following non-limiting examples.

[0041] Example

[0042] Phase 3 clinical study of troriluzole in adult subjects with spinocerebellar ataxia

[0043] Brief summary :

[0044] The aim of this study was to compare the efficacy of troluzole (200 mg once daily) with placebo after 48 weeks of treatment in subjects with spinocerebellar ataxia (SCA).

[0045] Condition or disease :

[0046] Spinocerebellar ataxia

[0047] Spinocerebellar ataxia type 1

[0048] Spinocerebellar ataxia type 2

[0049] Spinocerebellar ataxia type 3

[0050] Spinocerebellar ataxia type 6

[0051] Spinocerebellar ataxia type 7

[0052] Spinocerebellar ataxia type 8

[0053] Spinocerebellar ataxia type 10

[0054] Intervention / treatment :

[0055] Troluzole

[0056] Placebo

[0057] Study Design :

[0058] Study Type: Intervention (clinical trial)

[0059] Actual recruitment: 218 participants

[0060] Allocation: Randomization

[0061] Intervention Model: Parallel Assignment

[0062] Blinding: Triple-blind (participant, care provider, investigator)

[0063] Main purpose: Treatment

[0064] Official title: A Phase III, long-term, randomized, double-blind, placebo-controlled trial of troriluzole in adult subjects with spinocerebellar ataxia.

[0065] Arm and Intervention :

[0066] arm

[0067] Experiment: Arm 1: BHV-4157

[0068] Oral troriluzole 200 mg

[0069] Placebo Comparator: Arm 2: Placebo

[0070] Placebo 200 mg orally

[0071] Intervention / treatment

[0072] Drug: Troluzole

[0073] 200 mg orally

[0074] Drug: Placebo

[0075] 200 mg orally

[0076] Outcome indicators

[0077] Main outcome measures

[0078] 1. Change from baseline in the total score of the modified Functional Scale for Assessment and Rating of Ataxia (f-SARA) after 48 weeks of treatment. [Time range: baseline to week 48]

[0079] An increase in the total score indicates worsening symptoms.

[0080] Secondary outcome measures

[0081] 1. Change from baseline in the Patient Impression of Function and Activities of Daily Living Scale (PIF AS) score at Week 48 of the randomization phase. [Time range: Baseline to Week 48]

[0082] An increase in the total score indicates worsening symptoms.

[0083] 2. Change from baseline in the Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) score at Week 48 after randomization. [Time range: Baseline to Week 48]

[0084] An increase in the total score indicates worsening symptoms.

[0085] 3. Change from baseline in the Friedreich Ataxia Rating Scale-based functional stage (FARS-FUNC) at Week 48 of the randomization phase. [Time range: Baseline to Week 48]

[0086] An increase in the total score indicates worsening symptoms.

[0087] 4. Frequency of subjects with the following adverse events (AEs) as determined from case report forms: AEs (by severity; by relationship to study drug; overall); SAEs; and AEs leading to treatment discontinuation. [Time frame: Baseline to Week 48]

[0088] Eligibility Criteria

[0089] Inclusion criteria

[0090] 1. Subjects with a known or suspected diagnosis of the following specific inherited ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA10; currently only SCA 1, SCA2, SCA3, SCA7, and SCA10 are recruited (SCA6 and SCA8 have reached their cap (May 31, 2019));

[0091] a. The subject should have a confirmed genotypic diagnosis from a CLIA-certified laboratory that can generate test results; or

[0092] b. The subject has a family member with a confirmed genotypic diagnosis from a CLIA-certified laboratory that can generate test results and must be willing to undergo genetic testing to confirm a potential SCA diagnosis; or

[0093] c. The subject has a confirmed genotypic diagnosis from a non-CLIA certified laboratory and must be willing to undergo genetic testing to confirm a potential SCA diagnosis; or

[0094] d. The subject has clinical evidence supporting a diagnosis of one of the foregoing SCA genotypes, but does not have a family member or his or her own test results that can be generated from a CLIA-certified laboratory, and the subject must be willing to undergo such testing to confirm the SCA diagnosis (in this case, the site must await the results of the genotype test before randomization).

[0095] 2. Ability to walk 8 meters without human assistance (canes and other devices are permitted).

[0096] 3. The total f-SARA score should be ≥3.

[0097] 4. The gait subcomponent score of f-SARA is ≥ 1.

[0098] 5. Medically stable at baseline / randomization as determined by the investigator based on evaluation of medical history, physical examination, laboratory test results, and electrocardiogram.

[0099] Exclusion criteria

[0100] 1. The difference in modified functional SARA score between screening and baseline is ≥ 2 points.

[0101] 2.MMSE score <24.

[0102] 3. Any medical condition other than one of the hereditary ataxias specified in the inclusion criteria that could primarily explain or significantly contribute to the subject's ataxia symptoms.

[0103] 4. Marked spasticity or dystonia that, in the opinion of the investigator, would impair the ability of the SARA instrument to assess the severity of the underlying ataxia.

[0104] 5. Any single item of f-SARA (items 1-4) has a score of 4.

[0105] 6. Subjects should be excluded at screening or baseline if they have developed a medical condition or a change in disease state that could confound the ability of SARA to accurately reflect changes in ataxia severity.

[0106] 7. History of medically significant active liver disease or drug hepatic intolerance based on the investigator's judgment.

[0107] result

[0108] The primary endpoint, the change from baseline to Week 48 on the modified Functional Rating and Assessment of Ataxia (f-SARA), did not reach statistical significance in the overall SCA population because of a lower-than-expected reduction in disease progression during the study. In the overall study population (N=213), the mean baseline score on f-SARA was 4.9 for both the troriluzole and placebo groups, and both groups showed minimal changes at the Week 48 endpoint, with f-SARA scores of 5.1 and 5.2, respectively (p=0.76). Figure 1 Shown in.

[0109] Post hoc analyses of efficacy measures by genotype showed a treatment effect in patients with the SCA type 3 (SCA3) genotype, the most common form of SCA. Figure 2 ), troriluzole showed a numerical treatment benefit compared with placebo on the change from baseline to Week 48 in f-SARA scores (least squares [LS] mean change difference -0.55, nominal p-value = 0.053, 95% CI: -1.12, 0.01). In addition, in the SCA3 subgroup of patients who were able to walk without assistance at baseline (i.e., f-SARA gait item score = 1) ( Figure 3), troriluzole demonstrated a greater numerical treatment benefit in the change in f-SARA score from baseline to week 48 compared with placebo (LS mean change difference -0.71, nominal p-value = 0.031, 95% CI: -1.36, -0.07). It should be noted that f-SARA is a novel 16-point scale developed in collaboration with the FDA as the primary outcome measure of this trial; the scale was designed to limit subjective scales and focus on functional aspects of the disease so that significant changes are considered clinically meaningful.

[0110] SCA3 genotype analysis also showed a reduced relative risk of falls in patients treated with troriluzole compared with placebo (nominal p=0.04). Patient-reported falls, as measured by adverse events, revealed an approximately 50% reduction in the risk of falls in the troriluzole group (the AE incidence of falls was 16% vs. 32% in the troriluzole and placebo groups, respectively).

[0111] Across all genotypes, patients who were ambulatory at baseline (i.e., f-SARA gait item score = 1) showed a reduction in the relative risk of falls in patients treated with troriluzole compared with placebo. Patient-reported falls, as measured by adverse events, revealed a reduction in the risk of falls of approximately 59% in the troriluzole group (the AE incidence of falls in the troriluzole and placebo groups was 10% vs. 23%, respectively; nominal p = 0.043). Overall, troriluzole demonstrated a favorable safety and tolerability profile consistent with past clinical trial experience.

[0112] Throughout this application, various publications are cited by author name and date or by patent number or patent publication number. The disclosures of these publications are hereby incorporated by reference in their entirety into this application in order to more fully describe the prior art known to those skilled in the art as of the date of the invention described and claimed herein. However, citation of references herein should not be construed as an admission that such references are prior art to the present invention.

[0113] Those skilled in the art will recognize or be able to determine many equivalents of the specific procedures described herein using no more than routine experiments. Such equivalents are considered to be within the scope of the present invention and are covered by the following claims. For example, pharmaceutically acceptable salts other than those specifically disclosed in the description and embodiments herein may be used. In addition, it is contemplated that specific items within a list of items or item sub-cluster groups within a larger item group may be combined with other specific items, item sub-cluster groups, or larger item groups, regardless of whether there is a specific disclosure identifying such a combination herein.

Claims

1. A method for treating spinocerebellar ataxia genotype 3 in a patient in need thereof, the method comprising administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate.

2. The method of claim 1, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for forty-eight weeks, and wherein, Compared to placebo, the patients demonstrated a least squares [LS] mean change difference of -0.55 at Week 48 (nominal p-value = 0.053, 95% CI: -1.12, 0.01).

3. The method of claim 1, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily to a patient who is able to walk without assistance at baseline for forty-eight weeks, and wherein, Compared to placebo, the patients demonstrated a least squares [LS] mean change difference of -0.71 at Week 48 (nominal p-value = 0.031, 95% CI: -1.36, -0.07).

4. The method of claim 1, wherein the dosage form is in the form of a capsule.

5. The method of claim 1, wherein the dosage form is in the form of a tablet. The method according to claim 5 , wherein the tablet is an orally disintegrating tablet.

7. The method of claim 1, wherein the dosage form comprises 200 mg of troriluzole hydrochloride monohydrate, and wherein the dosage form is administered to the patient daily.

8. The method of claim 1, wherein the dosage form comprises 100 mg of troriluzole hydrochloride monohydrate, and wherein the dosage form is administered to the patient twice daily.

9. The method of claim 1, wherein the dosage form is administered daily for at least four weeks.

10. The method of claim 9, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for four weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.46 at Week 4 compared to placebo.

11. The method of claim 9, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered daily for four weeks to a patient who is able to walk without assistance at baseline, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.67 at Week 4 compared to placebo.

12. The method of claim 1, wherein the dosage form is administered daily for at least eight weeks.

13. The method of claim 12, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for eight weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.12 at Week 8 compared to placebo.

14. The method of claim 12, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for eight weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.33 at Week 8 compared to placebo.

15. The method of claim 1, wherein the dosage form is administered daily for at least twelve weeks.

16. The method of claim 15, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twelve weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.46 at Week 12 compared to placebo.

17. The method of claim 15, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twelve weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.71 at Week 12 compared to placebo.

18. The method of claim 1, wherein the dosage form is administered daily for at least twenty-four weeks.

19. The method of claim 18, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twenty-four weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.17 at Week 24 compared to placebo.

20. The method of claim 18, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twenty-four weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.40 at Week 24 compared to placebo.

21. The method of claim 1, wherein the dosage form is administered daily for at least thirty-six weeks.

22. The method of claim 21, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for thirty-six weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.72 at Week 36 compared to placebo.

23. The method of claim 21, wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for thirty-six weeks, and wherein, The patients demonstrated a least squares [LS] mean change difference of at least -0.55 at Week 36 compared to placebo.

24. The method of claim 1, wherein the dosage form is administered daily for at least forty-eight weeks.

25. The method of claim 24, wherein the dosage form is administered daily for an additional forty-eight weeks.

26. A dosage form comprising troriluzole hydrochloride monohydrate in an amount effective for treating spinocerebellar ataxia genotype 3 in a patient in need thereof.

27. The dosage form according to claim 26, comprising troriluzole hydrochloride monohydrate in an amount of 100 mg or more.

28. The dosage form according to claim 26, comprising troriluzole hydrochloride monohydrate in an amount of 140 mg or more.

29. The dosage form according to claim 26, comprising troriluzole hydrochloride monohydrate in an amount of 200 mg or more.

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