Study of SPARC1103 in Subjects With Spasticity

• Sponsor: Sun Pharma Advanced Research Company Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02027025
• Collaborator: (none)
• Enrollment: 142
• Locations: 23
• Arms: 3
• Actual Duration (Months): 36.2
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Study of SPARC1103 in subjects with spasticity

Condition or Disease	Intervention/Treatment	Phase
Spasticity	Drug: SPARC1103 low dose; Drug: SPARC1103 high dose; Drug: SPARC Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: Apr 21, 2014
• Actual Primary Completion Date: Apr 28, 2017
• Actual Study Completion Date: Apr 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SPARC 1103 low dose The subjects will receive SPARC 1103 low dose	Drug: SPARC1103 low dose; once daily
Active Comparator: SPARC1103 high dose The subjects will receive SPARC1103 high dose	Drug: SPARC1103 high dose; once daily
Placebo Comparator: SPARC Placebo The subjects will receive SPARC Placebo	Drug: SPARC Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

2. 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

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SPARC Site 4	Long Beach	California	United States
2	SPARC Site 6	San Diego	California	United States
3	SPARC Site 10	Aurora	Colorado	United States
4	SPARC Site 2	Jacksonville	Florida	United States
5	SPARC Site 7	Miami Springs	Florida	United States
6	SPARC Site 15	Miami	Florida	United States
7	SPARC Site 5	Orlando	Florida	United States
8	SPARC Site 13	Tampa	Florida	United States
9	SPARC Site 11	Kansas City	Kansas	United States
10	SPARC Site 3	Lenexa	Kansas	United States
11	SPARC Site 1	Bingham Farms	Michigan	United States
12	SPARC Site 14	Albuquerque	New Mexico	United States
13	SPARC Site 9	Charlotte	North Carolina	United States
14	SPARC Site 8	Cleveland	Ohio	United States
15	SPARC Site 12	Richland	Washington	United States
16	SPARC Site 18	Moscow		Russian Federation
17	SPARC Site 17	Nizhniy Novgorod		Russian Federation
18	SPARC Site 20	Samara		Russian Federation
19	SPARC Site 19	Smolensk		Russian Federation
20	SPARC Site 16	Ufa		Russian Federation
21	SPARC Site 22	Dnepropetrovsk		Ukraine
22	SPARC Site 21	Ivano-Frankivs'k		Ukraine
23	SPARC Site 23	L'viv		Ukraine

Sponsors and Collaborators

• Sun Pharma Advanced Research Company Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 31, 2017

More Information

Publications

None provided.

• Responsible Party: Sun Pharma Advanced Research Company Limited
• ClinicalTrials.gov Identifier: NCT02027025
• Other Study ID Numbers: CLR_11_03
• First Posted: Jan 3, 2014
• Last Update Posted: May 3, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sun Pharma Advanced Research Company Limited: Spasticity, Multiple sclerosis
• Additional relevant MeSH terms: Muscle Spasticity

Study Results

Participant Flow

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo
Arm/Group Description	SPARC1103 low dose dosing regimen: 1 capsule orally, approximately 30 minutes	SPARC1103 high dose dosing regimen 1 capsule orally, approximately 30 minutes	SPARC Placebo dosing regimen 1 capsule orally, approximately 30 minutes
Period Title: Overall Study
STARTED	48	47	47
COMPLETED	47	42	46
NOT COMPLETED	1	5	1

Baseline Characteristics

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo	Total
Arm/Group Description	Age: 50.5 (9.12)	Age: 52.3 (9.33)	Age: 50.2 (10.43)	Total of all reporting groups
Overall Participants	48	47	47	142
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.5 (9.12)	52.3 (9.33)	50.2 (10.43)	51.0 (9.62)
Sex: Female, Male (Count of Participants)
Female	23 47.9%	29 61.7%	28 59.6%	80 56.3%
Male	25 52.1%	18 38.3%	19 40.4%	62 43.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.1%	0 0%	0 0%	1 0.7%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	9 18.8%	2 4.3%	5 10.6%	16 11.3%
White	37 77.1%	45 95.7%	42 89.4%	124 87.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.1%	0 0%	0 0%	1 0.7%
Region of Enrollment (participants) [Number]
United States	48 100%	47 100%	47 100%	142 100%

Outcome Measures

1. Primary Outcome

Title	Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Modified Ashworth Score
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC1103 low dose, N=47; SPARC 1103 high hose, N=42; and Placebo, N=46

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose
Arm/Group Description	Least square mean difference (Placebo versus SPARC 1103 low dose) in change from baseline in total modified Ashworth score on day 24	Least square mean difference (Placebo versus SPARC 1103 high dose) in change from baseline in total modified Ashworth score on day 24
Measure Participants	47	42
Least Squares Mean (Standard Error) [score on a scale]	0.33 (1.47)	0.03 (1.53)

2. Secondary Outcome

Title	Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Night Time Awakening Score
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC 1103 low dose, N=47; SPARC 1103 high dose, N=42; and Placebo N=46.

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo
Arm/Group Description	Least square mean difference (Placebo versus SPARC 1103 low dose) in change from baseline in nighttime awakening score on day 24	Least square mean difference (Placebo versus SPARC 1103 high dose) in change from baseline in nighttime awakening score on day 24	Change from baseline for nighttime awakening score on day 24
Measure Participants	47	42	46
Least Squares Mean (Standard Error) [Awakenings]	-0.25 (0.449)	-0.24 (0.470)	0.23 (0.449)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 Low Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4532
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.73 to 0.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.64
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 High Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4704
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -1.76 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.65
	Estimation Comments

3. Secondary Outcome

Title	Least Square Mean Difference (Placebo Versus Each SPARC1103 Dose) in Change From Baseline in Spasm Frequency
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC 1103 low dose, N= 47; SPARC1103 High dose, N=42; and Placebo, N=46

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo
Arm/Group Description	Least square mean difference (Placebo versus SPARC 1103 low dose) in change from baseline in spasm frequency on day 24	Least square mean difference (Placebo versus SPARC 1103 high dose) in change from baseline in spasm frequency on day 24	Least square mean change from baseline in spasm frequency on day 24
Measure Participants	47	42	46
Least Squares Mean (Standard Error) [score on a scale]	-0.46 (0.129)	-0.46 (0.140)	-2.6 (0.133)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 Low Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3013
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 High Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2994
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.58 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

4. Secondary Outcome

Title	Clinical Global Impression of Change Results at 24 Hours Post Dose on Day 24
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC 1103 low dose, N=47; SPARC 1103 high dose, N=42; and Placebo N=46

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo
Arm/Group Description	Clinical global impression of change results at 24 hours post dose on Day 24	Clinical global impression of change results at 24 hours post dose on Day 24	Clinical global impression of change results at 24 hours post dose on Day 24
Measure Participants	47	42	46
CGIC - very much improved	4 8.3%	2 4.3%	3 6.4%
CGIC - much improved	12 25%	8 17%	8 17%
CGIC - minimally improved	16 33.3%	20 42.6%	26 55.3%
CGIC - no change	11 22.9%	6 12.8%	7 14.9%
CGIC - minimally worse	3 6.3%	5 10.6%	2 4.3%
CGIC - much worse	1 2.1%	1 2.1%	0 0%
CGIC - very much worse	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 Low Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3815
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 High Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7491
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Subject Global Impression of Severity of Spasticity
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC1103 low dose, N=47; SPARC1103 high dose, N=42; and Placebo, N=46

Arm/Group Title	SPARC1103 Low Dose	SPARC1103 High Dose	SPARC Placebo
Arm/Group Description	Subject's global impression of severity of spasticity at Day 24	Subject's global impression of severity of spasticity at Day 24	Subject's global impression of severity of spasticity at Day 24
Measure Participants	47	42	46
Normal - no spasticity	5 10.4%	4 8.5%	4 8.5%
Borderline spasticity	4 8.3%	5 10.6%	6 12.8%
Mild spasticity	15 31.3%	19 40.4%	15 31.9%
Moderate spasticity	19 39.6%	12 25.5%	18 38.3%
Marked spasticity	4 8.3%	1 2.1%	2 4.3%
Severe spasticity	0 0%	1 2.1%	1 2.1%
Worst spasticity imaginable	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 Low Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8991
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SPARC1103 High Dose, SPARC Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8829
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Screening through Day 24
Arm/Group Title	SPARC1103 Low Dose		SPARC1103 High Dose		SPARC Placebo
Arm/Group Description	Subjects with treatment emergent adverse events		Subjects with treatment emergent adverse events		Subjects with treatment emergent adverse events
All Cause Mortality
	SPARC1103 Low Dose		SPARC1103 High Dose		SPARC Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/47 (0%)		0/47 (0%)
Serious Adverse Events
	SPARC1103 Low Dose		SPARC1103 High Dose		SPARC Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		1/47 (2.1%)		0/47 (0%)
Infections and infestations
Influenza	0/48 (0%)		1/47 (2.1%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	SPARC1103 Low Dose		SPARC1103 High Dose		SPARC Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/48 (8.3%)		2/47 (4.3%)		0/47 (0%)
Gastrointestinal disorders
Nausea	2/48 (4.2%)		2/47 (4.3%)		0/47 (0%)
Nervous system disorders
headache	2/48 (4.2%)		0/47 (0%)		0/47 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.