Spasticity
Conditions
Keywords
spasticity
Brief summary
The purpose of this study is to assess whether SPARC0921 demonstrate efficacy and safety in the treatment of spasticity.
Interventions
DRUGSPARC0921
DRUGPlacebo0921
Sponsors
Sun Pharma Advanced Research Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women age 18 years and older * Able and willing to comply with the protocol, including availability for a scheduled clinic visits * Willingness and giving of written informed consent
Exclusion criteria
* In relapse or history of unstable course over the prior 30 days prior to the Screening Visit * Concomitant neurologic conditions causing spasticity * Has received an investigational drug or device within 30 days that would interfere with the study goals prior to the Screening Visit * Unable to comply with study procedures in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Failure Rate | Week 22 | Percentage of subjects who had treatment failure Clinical Global Impression of Change of ≥ 5 and at least one movement with ≥ 1 unit increase in modified Ashworth score from baseline. The modified Ashworth scale is a 6-point scale as follows: Minimum score of 0 (better outcome) = no increase in tone Maximum score of 4 (worst outcome) = affected part(s) rigid inflexion or extension. The clinician (other than the one performing the Modified Ashworth Scale assessment) rated his/her overall (global) impression of change in spasticity using the 7-point scale shown below: Minimum score of 1 (better outcome) = very much improved Maximum score of 7 (very much worse) = very much worse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Week 22 | The subject was asked Overall, how would you rate the severity of your spasticity over the past 24 hours? The 7-point scale for Subject's global impression of severity assessment is as follows: minimum score of 1 = normal, no spasticity maximum score of 7 (worst outcome)= worst spasticity imaginable |
Countries
Germany, Hungary, Russia, Ukraine, United States
Participant flow
Pre-assignment details
The study was conducted in part 1, 2, and 3: Part 1: 392 subjects Part 2: 376 subjects (SPARC0921), one death occurred in Part 2 of the study. Part 3: 296 subjects (SPARC0921 or Placebo0921) Efficacy results are presented for Part 3 and safety results are presented for Part 2 and Part 3 of the study as per the objectives of the study.
Participants by arm
| Arm | Count |
|---|---|
| SPARC0921 SPARC0921 Subjects who received SPARC0921 Dose Regimen I at Visit 1: 392 Received SPARC0921 Dose Regimen II at Visit 2 (Safety Population): 376 Randomized at Visit 7 to receive Dose Regimen III: 147 | 147 |
| Placebo0921 Placebo0921
Randomized at Visit 7: 149 | 146 |
| Total | 293 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 0 |
| Period 1 | Did not meet eligibility criteria | 3 | 0 |
| Period 1 | MS related disease progression | 1 | 0 |
| Period 1 | Physician Decision | 2 | 0 |
| Period 1 | Protocol Violation | 4 | 0 |
| Period 1 | Withdrawal by Subject | 2 | 0 |
| Period 1 | Withdrawn | 1 | 0 |
| Period 1 | withdrew per sponsor | 1 | 0 |
| Period 2 | Adverse Event | 22 | 0 |
| Period 2 | Did not meet eligibility criteria | 3 | 0 |
| Period 2 | dose change | 1 | 0 |
| Period 2 | Lack of Efficacy | 8 | 0 |
| Period 2 | Lost to Follow-up | 1 | 0 |
| Period 2 | no analysis | 10 | 0 |
| Period 2 | Physician Decision | 1 | 0 |
| Period 2 | Protocol Violation | 4 | 0 |
| Period 2 | Sponsor's withdrawal | 7 | 0 |
| Period 2 | Withdrawal by Subject | 23 | 0 |
| Period 3 | Adverse Event | 1 | 1 |
| Period 3 | incorrect treatment | 0 | 1 |
| Period 3 | Sponsor's withdrawal | 0 | 1 |
| Period 3 | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | SPARC0921 | Total | Placebo0921 |
|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 10.39 | 49.9 years STANDARD_DEVIATION 9.95 | 51.0 years STANDARD_DEVIATION 9.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 20 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 273 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 34 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 131 Participants | 253 Participants | 122 Participants |
| Sex: Female, Male Female | 105 Participants | 204 Participants | 99 Participants |
| Sex: Female, Male Male | 42 Participants | 89 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 0 / 149 | 1 / 376 | 0 / 392 |
| other Total, other adverse events | 23 / 147 | 25 / 149 | 226 / 376 | 6 / 392 |
| serious Total, serious adverse events | 3 / 147 | 0 / 149 | 12 / 376 | 0 / 392 |
Outcome results
Primary
Treatment Failure Rate
Percentage of subjects who had treatment failure Clinical Global Impression of Change of ≥ 5 and at least one movement with ≥ 1 unit increase in modified Ashworth score from baseline. The modified Ashworth scale is a 6-point scale as follows: Minimum score of 0 (better outcome) = no increase in tone Maximum score of 4 (worst outcome) = affected part(s) rigid inflexion or extension. The clinician (other than the one performing the Modified Ashworth Scale assessment) rated his/her overall (global) impression of change in spasticity using the 7-point scale shown below: Minimum score of 1 (better outcome) = very much improved Maximum score of 7 (very much worse) = very much worse
Time frame: Week 22
Population: Intent to treat population: SPARC0921, N=147 and and Placebo, N=146
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPARC0921 | Treatment Failure Rate | 36.1 percentage of subjects |
| Placebo0921 | Treatment Failure Rate | 43.2 percentage of subjects |
p-value: 0.2062Cochran-Mantel-Haenszel
Secondary
Severity of Spasticity Assessed by Subject Global Impression Severity Scale
The subject was asked Overall, how would you rate the severity of your spasticity over the past 24 hours? The 7-point scale for Subject's global impression of severity assessment is as follows: minimum score of 1 = normal, no spasticity maximum score of 7 (worst outcome)= worst spasticity imaginable
Time frame: Week 22
Population: Intent to treat population: SPARC0921, N=147 and Placebo0921, N=146
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Borderline spasticity | 6.8 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Marked spasticity | 15.0 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Mild spasticity | 26.5 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Severe spasticity | 4.1 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Normal, no spasticity | 19.7 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Worst spasticity imaginable | 0 percentage of subjects |
| SPARC0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Moderate spasticity | 27.9 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Worst spasticity imaginable | 2.1 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Borderline spasticity | 13 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Mild spasticity | 20.5 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Moderate spasticity | 33.6 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Marked spasticity | 14.4 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Severe spasticity | 6.2 percentage of subjects |
| Placebo0921 | Severity of Spasticity Assessed by Subject Global Impression Severity Scale | Normal, no spasticity | 10.3 percentage of subjects |
p-value: 0.0485Mantel Haenszel