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
Overview
- Phase
- Phase 3
- Intervention
- arbaclofen ER Tablets
- Conditions
- Multiple Sclerosis
- Sponsor
- RVL Pharmaceuticals, Inc.
- Locations
- 2
- Primary Endpoint
- Measure of sperm concentration according to WHO guidelines
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is designed to assess the effects of a therapeutic dose of arbaclofen extended release (ER) tablets compared with placebo on human sperm concentration, motility, and morphology in male subjects with multiple sclerosis (MS).
Detailed Description
Primary Objective: The primary safety objective is to assess the effects of arbaclofen ER tablets (AERT) compared with placebo on sperm concentration from baseline to the end of 90 days of treatment in male subjects with MS. Secondary Objectives: The secondary safety objectives are to assess: * The effects of AERT compared with placebo on the following sperm parameters from baseline to the end of 90 days of treatment in male subjects with MS: * Semen volume and total sperm count per ejaculate; * Sperm motility; * Sperm morphology; and * Plasma levels of reproductive hormones: Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone; * The recovery of subjects with 50 % decrease in sperm parameters 90 days after the discontinuation of IP; and * The safety and tolerability of IP.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For a subject to be eligible for participation in this study, all of the following criteria must be met at Screening:
- •Sign an informed consent form (ICF) indicating willingness and ability to participate in the study;
- •Be male and between 18 to 55 years old, inclusive, at the time of dosing;
- •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;
- •Has spasticity in the extremities that requires daily treatment with anti-spasticity drugs in the judgment of the Investigator;
- •Is able to have an erection and antegrade ejaculation with or without the use of phosphodiesterase 5 inhibitors (sildenafil, tadalfil, etc.);
- •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:
- •Semen volume \> or equal to 1.5 mL,
- •Total sperm per ejaculation \> or equal to 15 million,
- •Sperm concentration \> or equal to 10 million/mL,
Exclusion Criteria
- •Subjects will NOT be eligible for inclusion in the study if any of the following criteria apply:
- •Had an acute MS exacerbation requiring treatment within 6 weeks of Screening;
- •Has used intravenous methylprednisolone, or equivalent, within 6 weeks before Visit 1;
- •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);
- •Has other known reproductive disorders or an identifiable history of infertility:
- •Vasoligation (surgical ligation of the vas deferens as a means of sterilization);
- •Azoospermia or severe oligospermia, asthenospermia, teratospermia, leukocytospermia, or any combination of these at baseline; or
- •Retrograde ejaculation;
- •Has had a sexually transmitted disease within the last year;
- •Has severe spasticity that makes the use of placebo medication inappropriate in the judgment of the Investigator;
Arms & Interventions
Arbaclofen ER Tablets
AERT 10 mg twice daily (BID) (20 mg/day) for 7 days, followed by AERT 15 mg BID (30 mg/day) for 7 days
Intervention: arbaclofen ER Tablets
Placebo for Arbaclofen ER Tablets
Matching placebo AERT 10 mg twice daily (BID) (20 mg/day) for 7 days, followed by matching placebo AERT 15 mg BID (30 mg/day) for 7 days
Intervention: Placebo for arbaclofen ER tablets
Outcomes
Primary Outcomes
Measure of sperm concentration according to WHO guidelines
Time Frame: 90 days of treatment
The primary safety objective is to assess the effects of arbaclofen ER tablets (AERT) compared with placebo on sperm concentration from baseline to the end of 90 days of treatment in male subjects with MS. Analyses are performed by World Health Organization (WHO) guidelines (WHO, 2010) to obtain volume (mL), pH, sperm concentration motility, and morphology
Secondary Outcomes
- Measure of Semen volume per ejaculate according to the WHO guidelines(90 days of treatment)
- Measure of total sperm count per ejaculate according to the WHO guidelines(90 days of treatment)
- Measure of Sperm morphology according to the WHO guidelines(90 days of treatment)
- Measure of sperm motility according to the WHO guidelines(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(90 days of treatment)
- The recovery of subjects with 50% decrease in sperm parameters 90 days after the discontinuation of IP(90 days of treatment)