Spasticity
Conditions
Keywords
Spasticity, Multiple sclerosis
Brief summary
Study of SPARC1103 in subjects with spasticity
Interventions
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 greater than or equal to 18 years of age * Willing to sign the informed consent form * Women of child bearing potential willing to practice an acceptable method of birth control * Known history of spasticity due to MS
Exclusion criteria
* Administration of an investigational drug or device within 30 days prior to Screening Visit 1 * Unable to comply with trial procedures in the opinion of the Investigator * Concomitant neurologic conditions causing spasticity * Any medical condition, including psychiatric disease or epilepsy, which would interfere with the interpretation of the trial results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Modified Ashworth Score | Baseline, Day 24 | 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 in flexion or extension For calculation of modified Ashworth Score, the following scores were assigned to each category of modified Ashworth scale: not testable=NA, 0=0 units, 1=1 unit, 1+ = 2 units, 2 = 3 units, and 4 = 5 units. The total score was the sum of the scores of the 6 lower extremity muscle groups on both left and right sides (range = o0 to 60). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score | Baseline, Day 24 | Nighttime awakening score was assessed as follows: The subject was asked the following question on the morning of Day 24: How many times did you wake up last night due to spasticity? Score range from 0 (better score) to infinity (worse score) |
| Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency | Baseline, Day 24 | Spasm frequency was assessed using following 4-point scale as follows: Minimum score of 0 (better outcome))=no spasm Maximum score of 4 (worst outcome)=Spasms occurring more than 10 times per hour |
| Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | Baseline, Day 24 | 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 |
| Subject Global Impression of Severity of Spasticity | Baseline, Day 24 | 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
Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPARC1103 Low Dose Age: 50.5 (9.12) | 48 |
| SPARC1103 High Dose Age: 52.3 (9.33) | 47 |
| SPARC Placebo Age: 50.2 (10.43) | 47 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Sponsor's decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | SPARC1103 Low Dose | Total | SPARC Placebo | SPARC1103 High Dose |
|---|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 9.12 | 51.0 years STANDARD_DEVIATION 9.62 | 50.2 years STANDARD_DEVIATION 10.43 | 52.3 years STANDARD_DEVIATION 9.33 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 16 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 124 Participants | 42 Participants | 45 Participants |
| Region of Enrollment United States | 48 participants | 142 participants | 47 participants | 47 participants |
| Sex: Female, Male Female | 23 Participants | 80 Participants | 28 Participants | 29 Participants |
| Sex: Female, Male Male | 25 Participants | 62 Participants | 19 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 47 | 0 / 47 |
| other Total, other adverse events | 4 / 48 | 2 / 47 | 0 / 47 |
| serious Total, serious adverse events | 0 / 48 | 1 / 47 | 0 / 47 |
Outcome results
Primary
Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Modified Ashworth Score
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 in flexion or extension For calculation of modified Ashworth Score, the following scores were assigned to each category of modified Ashworth scale: not testable=NA, 0=0 units, 1=1 unit, 1+ = 2 units, 2 = 3 units, and 4 = 5 units. The total score was the sum of the scores of the 6 lower extremity muscle groups on both left and right sides (range = o0 to 60).
Time frame: Baseline, Day 24
Population: Intent to treat population: SPARC1103 low dose, N=47; SPARC 1103 high hose, N=42; and Placebo, N=46
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPARC1103 Low Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Modified Ashworth Score | 0.33 score on a scale | Standard Error 1.47 |
| SPARC1103 High Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Modified Ashworth Score | 0.03 score on a scale | Standard Error 1.53 |
Secondary
Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24
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: Baseline, Day 24
Population: Intent to treat population:~SPARC 1103 low dose, N=47; SPARC 1103 high dose, N=42; and Placebo N=46
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much improved | 12 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally worse | 3 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - no change | 11 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much improved | 4 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much worse | 0 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much worse | 1 participants |
| SPARC1103 Low Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally improved | 16 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - no change | 6 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much improved | 2 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much improved | 8 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally improved | 20 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally worse | 5 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much worse | 1 participants |
| SPARC1103 High Dose | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much worse | 0 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally worse | 2 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much improved | 8 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much worse | 0 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - much worse | 0 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - no change | 7 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - minimally improved | 26 participants |
| SPARC Placebo | Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24 | CGIC - very much improved | 3 participants |
p-value: 0.3815Chi-squared
p-value: 0.7491Chi-squared
Secondary
Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score
Nighttime awakening score was assessed as follows: The subject was asked the following question on the morning of Day 24: How many times did you wake up last night due to spasticity? Score range from 0 (better score) to infinity (worse score)
Time frame: Baseline, Day 24
Population: Intent to treat population: SPARC 1103 low dose, N=47; SPARC 1103 high dose, N=42; and Placebo N=46.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPARC1103 Low Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score | -0.25 Awakenings | Standard Error 0.449 |
| SPARC1103 High Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score | -0.24 Awakenings | Standard Error 0.47 |
| SPARC Placebo | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score | 0.23 Awakenings | Standard Error 0.449 |
p-value: 0.453295% CI: [-1.73, 0.78]ANCOVA
p-value: 0.470495% CI: [-1.76, 0.82]ANCOVA
Secondary
Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency
Spasm frequency was assessed using following 4-point scale as follows: Minimum score of 0 (better outcome))=no spasm Maximum score of 4 (worst outcome)=Spasms occurring more than 10 times per hour
Time frame: Baseline, Day 24
Population: Intent to treat population:~SPARC 1103 low dose, N= 47; SPARC1103 High dose, N=42; and Placebo, N=46
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPARC1103 Low Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency | -0.46 score on a scale | Standard Error 0.129 |
| SPARC1103 High Dose | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency | -0.46 score on a scale | Standard Error 0.14 |
| SPARC Placebo | Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency | -2.6 score on a scale | Standard Error 0.133 |
p-value: 0.301395% CI: [-0.56, 0.17]ANCOVA
p-value: 0.299495% CI: [-0.58, 0.18]ANCOVA
Secondary
Subject Global Impression of Severity of Spasticity
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: Baseline, Day 24
Population: Intent to treat population: SPARC1103 low dose, N=47; SPARC1103 high dose, N=42; and Placebo, N=46
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Borderline spasticity | 4 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Marked spasticity | 4 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Moderate spasticity | 19 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Normal - no spasticity | 5 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Worst spasticity imaginable | 0 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Severe spasticity | 0 Participants |
| SPARC1103 Low Dose | Subject Global Impression of Severity of Spasticity | Mild spasticity | 15 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Moderate spasticity | 12 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Normal - no spasticity | 4 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Borderline spasticity | 5 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Mild spasticity | 19 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Marked spasticity | 1 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Severe spasticity | 1 Participants |
| SPARC1103 High Dose | Subject Global Impression of Severity of Spasticity | Worst spasticity imaginable | 0 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Marked spasticity | 2 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Borderline spasticity | 6 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Worst spasticity imaginable | 0 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Severe spasticity | 1 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Moderate spasticity | 18 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Mild spasticity | 15 Participants |
| SPARC Placebo | Subject Global Impression of Severity of Spasticity | Normal - no spasticity | 4 Participants |
p-value: 0.8991Chi-squared
p-value: 0.8829Chi-squared