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

• Register: ClinicalTrials.gov
• Last refreshed on: 2 May 2022
• Main ID: NCT02869425
• Date of registration: 03/08/2016
• Prospective Registration: No
• Primary sponsor: RVL Pharmaceuticals, Inc.
• Public title: To Assess Effects of Arbaclofen ER Tablets Compared With Placebo on Sperm Parameters in Male Subjects With MS
• Scientific title: A Randomized, Double-Blind, Parallel-Group Study to Assess the Effects of Arbaclofen ER Tablets Compared With Placebo on Sperm Parameters in Male Subjects With Multiple Sclerosis
• Date of first enrolment: July 2016
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02869425
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Sam Kaba, MD
• Affiliation: Osmotica Pharmaceutical, VP - Global Clinical Development and Medical Affairs

Key inclusion & exclusion criteria

Inclusion Criteria:

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

1. Sign an informed consent form (ICF) indicating willingness and ability to
participate 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, or
neuromyelitis optica) can be enrolled in the study if they meet all other
eligibility criteria;

4. Has spasticity in the extremities that requires daily treatment with
anti-spasticity drugs in the judgment of the Investigator;

5. Is able to have an erection and antegrade ejaculation with or without the use of
phosphodiesterase 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 the
following sperm eligibility criteria:

1. Semen volume > or equal to 1.5 mL,

2. Total sperm per ejaculation > or equal to 15 million,

3. Sperm concentration > or equal to 10 million/mL,

4. Total sperm motility > or equal to 19%, and

5. White blood cell count <3 million/mL,

7. Concomitant use of baclofen is permitted during Screening, but subjects must stop
baclofen on the day prior to randomization (Visit 3). All other prohibited
concomitant medications (Appendix D) must be discontinued prior to randomization
(Visit 3);

8. If receiving disease-modifying medications, these must have been at a stable dose
for at least 3 months prior to randomization;

9. All other medications, including AMPYRA® (e.g., dalfampridine, fampridine, 4
aminopyridine), must have been at a stable dose for at least 3 months prior to
randomization;

10. Absence of infections, peripheral vascular disease, contractures, advanced
arthritis, or other conditions that hinder evaluation of joint movement;

11. Has a creatinine clearance > or equal to 50 mL/min, as calculated by glomerular
filtration rate using the Modification of Diet in Renal Disease formula;

12. Be able to swallow tablets whole;

13. Be willing to abstain from ejaculation for at least 3 days prior to the
collection of each semen sample;

14. Subject and female partners must agree to use a birth control method while on IP
and until 30 days following the last administration of IP; and

15. 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 following
criteria apply:

1. Had an acute MS exacerbation requiring treatment within 6 weeks of Screening;

2. Has used intravenous methylprednisolone, or equivalent, within 6 weeks before
Visit 1;

3. Use of concomitant medications that would potentially interfere with the actions
of the IP or results of the outcome variables (Appendix D) must be stopped prior
to randomization. However, concomitant use of baclofen is permitted during
Screening, but subjects must stop baclofen on the day prior to randomization
(Visit 3). All other prohibited concomitant medications (Appendix D) must be
discontinued prior to randomization (Visit 3);

4. Has other known reproductive disorders or an identifiable history of infertility:

1. Vasoligation (surgical ligation of the vas deferens as a means of
sterilization);

2. Azoospermia or severe oligospermia, asthenospermia, teratospermia,
leukocytospermia, or any combination of these at baseline; or

3. Retrograde ejaculation;

5. Has had a sexually transmitted disease within the last year;

6. Has severe spasticity that makes the use of placebo medication inappropriate in
the judgment of the Investigator;

7. Has had radiation to the pelvic or groin area;

8. Has a condition that affects spermatogenesis, such as recent severe genitourinary
infections and prostatitis;

9. Has had previous prostate surgery or vasectomy;

10. Has been diagnosed by a urologist with any one of the following diseases:

1. Hydrocele of the tunica vaginalis;

2. Hematocele;

3. Torsion of the spermatic cord;

4. Torsion of the testicular appendage;

5. Varicocele II or more severe seminal vesiculitis;

6. Gangrene on the skin of the scrotum;

7. Cryptorchidism, small testis (12 mL, testicular volumes were determined by
use of a Prader orchidometer);

8. Congenital absence of the vas deferens;

9. Tuberculosis of the epididymis; or

10. Chronic prostatitis, defined as > or equal to 3 million/mL white blood cell
count in semen samples;

11. Has a history of unstable psychiatric disease, or current signs and symptoms of
significant medical disorders, such as severe, progressive, or uncontrolled
pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary,
hematological, endocrine, immunologic, or neurological disease;

12. Exhibits suicidality defined as active suicidal plan/intent or active suicidal
thoughts 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 or
suicidal ideation within 1 year of Screening as determined by the C-SSRS or
medical history or currently is at a serious suicidal risk in the judgment of the
Investigator);

13. Has seizure disorder;

14. Has significant cognitive deficit, severe or untreated anxiety, or severe or
untreated depression, which in the judgment of the Investigator, may interfere
with the ability of the subject to participate in the study;

15. Has a current malignancy or history of malignancy in the last 5 years, except
effectively treated basal cell skin c


Age minimum: 18 Years
Age maximum: 55 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Sperm

Multiple Sclerosis

Intervention(s)

Drug: Placebo for arbaclofen ER tablets

Drug: arbaclofen ER Tablets

Primary Outcome(s)

Measure of sperm concentration according to WHO guidelines [Time Frame: 90 days of treatment]

Secondary Outcome(s)

Measure of Sperm morphology according to the WHO guidelines [Time Frame: 90 days of treatment]

Measure of total sperm count per ejaculate according to the WHO guidelines [Time Frame: 90 days of treatment]

The recovery of subjects with 50% decrease in sperm parameters 90 days after the discontinuation of IP [Time Frame: 90 days of treatment]

Measure of Plasma levels of FSH, LH, and total testosterone values and their respective change from baseline values will be summarized by visit [Time Frame: 90 days of treatment]

Measure of sperm motility according to the WHO guidelines [Time Frame: 90 days of treatment]

Measure of Semen volume per ejaculate according to the WHO guidelines [Time Frame: 90 days of treatment]

Secondary ID(s)

OS440-PKP06

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Osmotica Pharmaceutical US LLC