A Safety and Efficacy Study of XP19986 in Subjects With Spasticity Due to Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of treatment with XP19986 Sustained Release (SR) Tablet compared to placebo in subjects with spasticity due to spinal cord injury

Detailed Description
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This is a multiple-dose, randomized, placebo-controlled crossover study of the efficacy and safety of XP19986 SR1 in subjects with spasticity due to spinal cord injury. Three cohorts of subjects are randomized to receive XP19986 SR1 10 mg every 12 hrs or 20 mg every 12 hrs or 30 mg every 12 hrs in one treatment segment and placebo every 12 hrs in the alternate treatment segment. Each subject serves as their own control in this cross-over study.

Official Title
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Multiple-Dose Efficacy and Safety Study of XP19986 in Subjects With Spasticity Due to Spinal Cord Injury

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Drug: XP19986 SR1, 10 mg BID
* Drug: XP19986 SR1, 20 mg BID
* Drug: XP19986 SR1, 30 mg BID
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spasticity secondary to traumatic spinal cord injury between C-5 and T-12 spinal cord levels, at least 12 months post-injury with a stable neurological deficit Exclusion Criteria: Traumatic brain injury or cognitive deficit of any etiology that may influence compliance with study procedures or outcome measures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XP19986 SR1 10 mg - Placebo<br>Following a 7 day run-in period in which participants take placebo twice a day (BID), participants are randomized to the cohort that will take XP19986 SR1 10 mg BID treatment crossing over to placebo treatment (or the reverse order). Each treatment segment follows the same pattern: 3-9 days of titration, 7 days at target dose, 3-9 days of tapering, followed by a 3-day placebo washout. | Drug: XP19986 SR1, 10 mg BID<br>* XP19986 Sustained Release (SR) 10 mg tablet dosed orally, twice a day (BID), for approximately 26 days with titration and taper periods<br>* Other names: Sustained release Polyox WSR N750, 10 mg;Drug: Placebo<br>* Placebo tablets to match active intervention, taken twice a day (BID) for approximately 26 days with titration and taper periods. Also taken during placebo washout periods.<br>* Other names: sugar pill;|
| Experimental: XP19986 SR1 20 mg - Placebo<br>Following a 7 day run-in period in which participants take placebo twice a day (BID), participants are randomized to the cohort that will take XP19986 SR1 20 mg BID treatment crossing over to placebo treatment (or the reverse order). Each treatment segment follows the same pattern: 3-9 days of titration, 7 days at target dose, 3-9 days of tapering, followed by a 3-day placebo washout. | Drug: XP19986 SR1, 20 mg BID<br>* XP19986 Sustained Release (SR) 20 mg tablet dosed orally, twice a day (BID), for approximately 26 days with titration and taper periods<br>* Other names: Sustained release Polyox WSR N750, 20 mg;Drug: Placebo<br>* Placebo tablets to match active intervention, taken twice a day (BID) for approximately 26 days with titration and taper periods. Also taken during placebo washout periods.<br>* Other names: sugar pill;|
| Experimental: XP19986 SR1 30 mg - Placebo<br>Following a 7 day run-in period in which participants take placebo twice a day (BID), participants are randomized to the cohort that will take XP19986 SR1 30 mg BID treatment crossing over to placebo treatment (or the reverse order). Each treatment segment follows the same pattern: 3-9 days of titration, 7 days at target dose, 3-9 days of tapering, followed by a 3-day placebo washout. | Drug: XP19986 SR1, 30 mg BID<br>* XP19986 Sustained Release (SR) 30 mg tablet dosed orally, twice a day (BID), for approximately 26 days with titration and taper periods<br>* Other names: Sustained release Polyox WSR N750, 30 mg;Drug: Placebo<br>* Placebo tablets to match active intervention, taken twice a day (BID) for approximately 26 days with titration and taper periods. Also taken during placebo washout periods.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Ashworth score | Ashworth score for each treatment segment before dosing and 2, 4, and 6 hours after the morning dose. Evaluate the difference in the primary endpoint between active and placebo treament segments at 17th day of dosing in each segment | Day 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Ashworth score | This was the average of Ashworth scores obtained on Day 17 of dosing across 6 muscle groups for each treatment segment before dosing and 2, 4, and 6 hours after the morning dose | Day 17 | 
| Two Highest Ashworth scores | This was the average of Ashworth scores obtained on Day 17 of dosing from the muscle groups that had the 2 highest Ashworth scores at baseline for each treatment segment before dosing and 2, 4, and 6 hours after the morning dose | Day 17 | 
| Average Non-zero Ashworth Scores | This was the average of Ashworth scores obtained on Day 17 of dosing from the muscle groups that had a non-zero Ashworth score at baseline for each treatment segment before dosing and 2, 4, and 6 hours after the morning dose | Day 17 |