To Assess Effects of Arbaclofen ER Tablets Compared With Placebo on Sperm Parameters in Male Subjects With MS

Inclusion Criteria:

• For a subject to be eligible for participation in this study, all of the followingcriteria must be met at Screening:

1. Sign an informed consent form (ICF) indicating willingness and ability toparticipate in the study;
2. Be male and between 18 to 55 years old, inclusive, at the time of dosing;
3. Has an established diagnosis of MS for >6 months; subjects with all types of MS (relapsing remitting, secondary-progressive, primary-progressive, orneuromyelitis optica) can be enrolled in the study if they meet all othereligibility criteria;
4. Has spasticity in the extremities that requires daily treatment withanti-spasticity drugs in the judgment of the Investigator;
5. Is able to have an erection and antegrade ejaculation with or without the use ofphosphodiesterase 5 inhibitors (sildenafil, tadalfil, etc.);
6. The average of each semen parameter (except volume) collected at Screening (Visits 1 and 2) will be calculated to determine if the subject meets thefollowing sperm eligibility criteria:
7. Semen volume > or equal to 1.5 mL,
8. Total sperm per ejaculation > or equal to 15 million,
9. Sperm concentration > or equal to 10 million/mL,
10. Total sperm motility > or equal to 19%, and
11. White blood cell count <3 million/mL,
12. Concomitant use of baclofen is permitted during Screening, but subjects must stopbaclofen on the day prior to randomization (Visit 3). All other prohibitedconcomitant medications (Appendix D) must be discontinued prior to randomization (Visit 3);
13. If receiving disease-modifying medications, these must have been at a stable dosefor at least 3 months prior to randomization;
14. All other medications, including AMPYRA® (e.g., dalfampridine, fampridine, 4aminopyridine), must have been at a stable dose for at least 3 months prior torandomization;
15. Absence of infections, peripheral vascular disease, contractures, advancedarthritis, or other conditions that hinder evaluation of joint movement;
16. Has a creatinine clearance > or equal to 50 mL/min, as calculated by glomerularfiltration rate using the Modification of Diet in Renal Disease formula;
17. Be able to swallow tablets whole;
18. Be willing to abstain from ejaculation for at least 3 days prior to thecollection of each semen sample;
19. Subject and female partners must agree to use a birth control method while on IPand until 30 days following the last administration of IP; and
20. If acquisition of a semen sample requires participation of the subject's partner,that partner must sign an informed consent and agree to participate in the study.

Exclusion Criteria:

• Subjects will NOT be eligible for inclusion in the study if any of the followingcriteria apply:

1. Had an acute MS exacerbation requiring treatment within 6 weeks of Screening;
2. Has used intravenous methylprednisolone, or equivalent, within 6 weeks beforeVisit 1;
3. Use of concomitant medications that would potentially interfere with the actionsof the IP or results of the outcome variables (Appendix D) must be stopped priorto randomization. However, concomitant use of baclofen is permitted duringScreening, but subjects must stop baclofen on the day prior to randomization (Visit 3). All other prohibited concomitant medications (Appendix D) must bediscontinued prior to randomization (Visit 3);
4. Has other known reproductive disorders or an identifiable history of infertility:
5. Vasoligation (surgical ligation of the vas deferens as a means ofsterilization);
6. Azoospermia or severe oligospermia, asthenospermia, teratospermia,leukocytospermia, or any combination of these at baseline; or
7. Retrograde ejaculation;
8. Has had a sexually transmitted disease within the last year;
9. Has severe spasticity that makes the use of placebo medication inappropriate inthe judgment of the Investigator;
10. Has had radiation to the pelvic or groin area;
11. Has a condition that affects spermatogenesis, such as recent severe genitourinaryinfections and prostatitis;
12. Has had previous prostate surgery or vasectomy;
13. Has been diagnosed by a urologist with any one of the following diseases:
14. Hydrocele of the tunica vaginalis;
15. Hematocele;
16. Torsion of the spermatic cord;
17. Torsion of the testicular appendage;
18. Varicocele II or more severe seminal vesiculitis;
19. Gangrene on the skin of the scrotum;
20. Cryptorchidism, small testis (12 mL, testicular volumes were determined byuse of a Prader orchidometer);
21. Congenital absence of the vas deferens;
22. Tuberculosis of the epididymis; or
23. Chronic prostatitis, defined as > or equal to 3 million/mL white blood cellcount in semen samples;
24. Has a history of unstable psychiatric disease, or current signs and symptoms ofsignificant medical disorders, such as severe, progressive, or uncontrolledpulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary,hematological, endocrine, immunologic, or neurological disease;
25. Exhibits suicidality defined as active suicidal plan/intent or active suicidalthoughts in the 6 months before Screening as defined by a suicidal ideation score > or equal to 3 on the C-SSRS, (Appendix B; Has a history of suicide attempts orsuicidal ideation within 1 year of Screening as determined by the C-SSRS ormedical history or currently is at a serious suicidal risk in the judgment of theInvestigator);
26. Has seizure disorder;
27. Has significant cognitive deficit, severe or untreated anxiety, or severe oruntreated depression, which in the judgment of the Investigator, may interferewith the ability of the subject to participate in the study;
28. Has a current malignancy or history of malignancy in the last 5 years, excepteffectively treated basal cell skin carcinoma;
29. Has advanced or uncontrolled diabetes, human immunodeficiency virus infection,history of hepatitis C or active hepatitis B, or any other significant disease,disorder, or significant laboratory finding which, in the judgment of theInvestigator, would put the subject at risk because of participation in thestudy, influence the result of the study, or affect the subject's ability toparticipate in the study;
30. Has planned elective surgery or other procedures requiring general anesthesiaduring the study;
31. Current chronic use of long-acting opioids or daily use of short-acting opioidsfor the treatment of pain;
32. Has participated in another interventional trial within 30 days of Screening;
33. Has a positive laboratory test result for hepatitis B surface antigen, hepatitisB core antibody, hepatitis C, or controlled substances; or
34. Has a history of alcohol dependence, substance abuse, or binge drinking. Thesubject should avoid heavy drinking during the weeks of sperm sample collection.