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

NCT02869425 | Withdrawn Phase 3

• 1 other identifier: OS440-PKP06
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Multiple Sclerosis; Sperm

Outcome Measures

Primary Outcomes (1)

• Measure of sperm concentration according to WHO guidelines

  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

  90 days of treatment

Secondary Outcomes (6)

• 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

• 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

Study Arms (2)

Arbaclofen ER Tablets

EXPERIMENTAL

AERT 10 mg twice daily (BID) (20 mg/day) for 7 days, followed by AERT 15 mg BID (30 mg/day) for 7 days

Drug: arbaclofen ER Tablets

Placebo for Arbaclofen ER Tablets

PLACEBO COMPARATOR

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

Drug: Placebo for arbaclofen ER tablets

Interventions

arbaclofen ER Tablets DRUG

arbaclofen ER tablets, 10 mg, 15 mg, or 20 mg

Also known as: AERT

Arbaclofen ER Tablets

Placebo for arbaclofen ER tablets DRUG

matching placebo tablets to arbaclofen ER tablets 10 mg, 15 mg or 20 mg

Also known as: Placebo

Placebo for Arbaclofen ER Tablets

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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,
• Total sperm motility \> or equal to 19%, and
• White blood cell count \<3 million/mL,
• 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);
• If receiving disease-modifying medications, these must have been at a stable dose for at least 3 months prior to randomization;
• 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;

You may not qualify if:

• 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;
• Has had radiation to the pelvic or groin area;
• Has a condition that affects spermatogenesis, such as recent severe genitourinary infections and prostatitis;
• Has had previous prostate surgery or vasectomy;
• Has been diagnosed by a urologist with any one of the following diseases:
• Hydrocele of the tunica vaginalis;
• Hematocele;

Sponsors & Collaborators

• Osmotica Pharmaceutical US LLC: collaborator
• RVL Pharmaceuticals, Inc.: lead

Study Sites (2)

Advance Medical Pain Management & Research Clinic

Miami, Florida, 33169, United States

Location

Meridien Research

Tampa, Florida, 33604, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Sam Kaba, MD

  Osmotica Pharmaceutical, VP - Global Clinical Development and Medical Affairs

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2016
• First Posted: August 17, 2016
• Study Start: July 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: January 1, 2019
• Last Updated: April 27, 2022

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)