Efficacy and Safety of SPARC0921 in Subjects With Spasticity

• Sponsor: Sun Pharma Advanced Research Company Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01457352
• Collaborator: (none)
• Enrollment: 392
• Locations: 73
• Arms: 2
• Actual Duration (Months): 57.3
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether SPARC0921 demonstrate efficacy and safety in the treatment of spasticity.

Condition or Disease	Intervention/Treatment	Phase
Spasticity	Drug: SPARC0921; Drug: Placebo0921	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 392 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: Nov 14, 2012
• Actual Primary Completion Date: Aug 25, 2017
• Actual Study Completion Date: Aug 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPARC0921	Drug: SPARC0921
Placebo Comparator: Placebo0921	Drug: Placebo0921

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SPARC site 6	Gilbert	Arizona	United States
2	SPARC Site 40	Phoenix	Arizona	United States
3	SPARC Site 36	Costa Mesa	California	United States
4	SPARC Site 20	Newport Beach	California	United States
5	SPARC Site 38	Basalt	Colorado	United States
6	SPARC Site 21	Denver	Colorado	United States
7	SPARC Site 9	Derby	Connecticut	United States
8	SPARC Site 57	Hartford	Connecticut	United States
9	SPARC Site 10	New London	Connecticut	United States
10	SPARC Site 60	Washington	District of Columbia	United States
11	SPARC Site 15	Bradenton	Florida	United States
12	SPARC Site 54	Jacksonville	Florida	United States
13	SPARC Site 41	Maitland	Florida	United States
14	SPARC Site 70	Miami	Florida	United States
15	SPARC Site 8	Ormond Beach	Florida	United States
16	SPARC Site 17	Port Charlotte	Florida	United States
17	SPARC Site 19	Sarasota	Florida	United States
18	SPARC Site 31	Sunrise	Florida	United States
19	SPARC Site 39	Tampa	Florida	United States
20	SPARC Site 65	Tampa	Florida	United States
21	SPARC Site 51	Lenexa	Kansas	United States
22	SPARC Site 30	Overland Park	Kansas	United States
23	SPARC Site 50	Louisville	Kentucky	United States
24	SPARC Site 42	Alexandria	Louisiana	United States
25	SPARC Site 27	Baton Rouge	Louisiana	United States
26	SPARC Site 73	New Orleans	Louisiana	United States
27	SPARC Site 35	Foxboro	Massachusetts	United States
28	SPARC Site 23	Springfield	Massachusetts	United States
29	SPARC Site 32	Clinton Township	Michigan	United States
30	SPARC Site 64	Detroit	Michigan	United States
31	SPARC Site 25	Golden Valley	Minnesota	United States
32	SPARC Site 5	Henderson	Nevada	United States
33	SPARC site 34	Flemington	New Jersey	United States
34	SPARC Site 55	Stratford	New Jersey	United States
35	SPARC Site 22	Albuquerque	New Mexico	United States
36	SPARC Site 49	Rochester	New York	United States
37	SPARC Site 45	Charlotte	North Carolina	United States
38	SPARC Site 4	Charlotte	North Carolina	United States
39	SPARC Site 24	Greensboro	North Carolina	United States
40	SPARC Site 2	Winston-Salem	North Carolina	United States
41	SPARC Site 75	Winston-Salem	North Carolina	United States
42	SPARC Site 16	Akron	Ohio	United States
43	SPARC Site 33	Centerville	Ohio	United States
44	SPARC Site 56	Columbus	Ohio	United States
45	SPARC Site 12	Eugene	Oregon	United States
46	SPARC Site 44	Springfield	Oregon	United States
47	SPARC Site 68	Abington	Pennsylvania	United States
48	SPARC Site 29	Indian Land	South Carolina	United States
49	SPARC Site 7	Austin	Texas	United States
50	SPARC Site 71	Dallas	Texas	United States
51	SPARC Site 43	Houston	Texas	United States
52	SPARC Site 13	Salt Lake City	Utah	United States
53	SPARC Site 26	Tacoma	Washington	United States
54	SPARC Site 74	Huntington	West Virginia	United States
55	SPARC Site 69	Milwaukee	Wisconsin	United States
56	SPARC Site 67	Waukesha	Wisconsin	United States
57	SPARC Site 77	Dresden		Germany
58	SPARC Site 76	Erbach		Germany
59	SPARC Site 79	Teupitz		Germany
60	SPARC Site 78	Westerstede		Germany
61	SPARC Site 82	Budapest		Hungary
62	SPARC site 83	Budapest		Hungary
63	SPARC Site 81	Eger		Hungary
64	SPARC Site 80	Esztergom		Hungary
65	SPARC Site 87	Moscow		Russian Federation
66	SPARC Site 86	Novosibirsk		Russian Federation
67	SPARC Site 85	Saint Petersburg		Russian Federation
68	SPARC Site 84	Sestroretsk		Russian Federation
69	SPARC Site 88	Stavropol'		Russian Federation
70	SPARC Site 90	Dnipropetrovsk		Ukraine
71	SPARC Site 92	L'viv		Ukraine
72	SPARC Site 91	Poltava		Ukraine
73	SPARC Site 89	Zaporozh'ye		Ukraine

Sponsors and Collaborators

• Sun Pharma Advanced Research Company Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 24, 2012
• Statistical Analysis Plan - Sep 21, 2017

More Information

Publications

None provided.

• Responsible Party: Sun Pharma Advanced Research Company Limited
• ClinicalTrials.gov Identifier: NCT01457352
• Other Study ID Numbers: CLR_09_21
• First Posted: Oct 21, 2011
• Last Update Posted: Jun 18, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Sun Pharma Advanced Research Company Limited: spasticity
• Additional relevant MeSH terms: Muscle Spasticity

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	SPARC0921	Placebo
Arm/Group Description	once, twice, thrice, or four times daily for one week	Placebo formulation
Period Title: Period 1
STARTED	392	0
COMPLETED	376	0
NOT COMPLETED	16	0
Period Title: Period 1
STARTED	376	0
COMPLETED	296	0
NOT COMPLETED	80	0
Period Title: Period 1
STARTED	147	149
Randomization	147	149
COMPLETED	146	144
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	SPARC0921	Placebo0921	Total
Arm/Group Description	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	Placebo0921 Randomized at Visit 7: 149	Total of all reporting groups
Overall Participants	147	146	293
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.8 (10.39)	51.0 (9.39)	49.9 (9.95)
Sex: Female, Male (Count of Participants)
Female	105 71.4%	99 67.8%	204 69.6%
Male	42 28.6%	47 32.2%	89 30.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 6.8%	10 6.8%	20 6.8%
Not Hispanic or Latino	137 93.2%	136 93.2%	273 93.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.7%	1 0.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 10.2%	19 13%	34 11.6%
White	131 89.1%	122 83.6%	253 86.3%
More than one race	1 0.7%	4 2.7%	5 1.7%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Treatment Failure Rate
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC0921, N=147 and and Placebo, N=146

Arm/Group Title	SPARC0921	Placebo0921
Arm/Group Description	SPARC0921	Placebo0921
Measure Participants	147	146
Number [percentage of subjects]	36.1	43.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC0921, Placebo0921
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2062
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Severity of Spasticity Assessed by Subject Global Impression Severity Scale
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	Week 22

Outcome Measure Data

Analysis Population Description

Intent to treat population: SPARC0921, N=147 and Placebo0921, N=146

Arm/Group Title	SPARC0921	Placebo0921
Arm/Group Description	Subject Global Impression of Severity of Spasticity in SPARC0921 group	Subject Global Impression of Severity of Spasticity in Placebo0921 group
Measure Participants	147	146
Normal, no spasticity	19.7	10.3
Borderline spasticity	6.8	13
Mild spasticity	26.5	20.5
Moderate spasticity	27.9	33.6
Marked spasticity	15.0	14.4
Severe spasticity	4.1	6.2
Worst spasticity imaginable	0	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SPARC0921, Placebo0921
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0485
	Comments
	Method	Mantel Haenszel
	Comments

Adverse Events

Time Frame	Week 22
Adverse Event Reporting Description	Part 2 and Part 3 safety data is displayed in the registry. Part A was a run-in period of the study.
Arm/Group Title	SPARC0921- Part 3		Placebo0921 - Part 3		SPARC 0921 - Part 2		Run-in Part 1
Arm/Group Description	SPARC0921 in randomized phase		Placebo0921 in randomized phase		Open label		Open label run-in period
All Cause Mortality
	SPARC0921- Part 3		Placebo0921 - Part 3		SPARC 0921 - Part 2		Run-in Part 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Serious Adverse Events
	SPARC0921- Part 3		Placebo0921 - Part 3		SPARC 0921 - Part 2		Run-in Part 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/147 (2%)		0/149 (0%)		12/376 (3.2%)		0/392 (0%)
Cardiac disorders
Acute myocardial infarction	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
General disorders
death	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Infections and infestations
Urinary tract infection	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Injury, poisoning and procedural complications
Hip fracture	1/147 (0.7%)	1	0/149 (0%)	0	0/376 (0%)	0	0/392 (0%)	0
Accidental overdose	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/147 (0.7%)	1	0/149 (0%)	0	0/376 (0%)	0	0/392 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Nervous system disorders
Syncope	1/147 (0.7%)	1	0/149 (0%)	0	0/376 (0%)	0	0/392 (0%)	0
Multiple sclerosis relapse	0/147 (0%)		0/149 (0%)		2/376 (0.5%)		0/392 (0%)
Encephalopathy	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Psychiatric disorders
Delirium	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Psychotic disorder	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Vascular disorders
Deep vein thrombosis	0/147 (0%)		0/149 (0%)		1/376 (0.3%)		0/392 (0%)
Other (Not Including Serious) Adverse Events
	SPARC0921- Part 3		Placebo0921 - Part 3		SPARC 0921 - Part 2		Run-in Part 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/147 (15.6%)		25/149 (16.8%)		226/376 (60.1%)		6/392 (1.5%)
Gastrointestinal disorders
Nausea	0/147 (0%)		0/149 (0%)		22/376 (5.9%)		1/392 (0.3%)
vomitting	0/147 (0%)		0/149 (0%)		9/376 (2.4%)		0/392 (0%)
Diarrhoea	2/147 (1.4%)		2/149 (1.3%)		6/376 (1.6%)		1/392 (0.3%)
General disorders
Fatigue	4/147 (2.7%)		0/149 (0%)		24/376 (6.4%)		0/392 (0%)
Oedema peripheral	0/147 (0%)		0/149 (0%)		10/376 (2.7%)		0/392 (0%)
Asthenia	0/147 (0%)		0/149 (0%)		6/376 (1.6%)		1/392 (0.3%)
Infections and infestations
Urinary tract infection	3/147 (2%)		6/149 (4%)		12/376 (3.2%)		1/392 (0.3%)
Nasopharyngitis	0/147 (0%)		4/149 (2.7%)		13/376 (3.5%)		0/392 (0%)
sinusitis	0/147 (0%)		0/149 (0%)		12/376 (3.2%)		0/392 (0%)
Investigations
Blood pressure increased	1/147 (0.7%)		4/149 (2.7%)		5/376 (1.3%)		1/392 (0.3%)
Musculoskeletal and connective tissue disorders
Muscle spasm	2/147 (1.4%)		4/149 (2.7%)		12/376 (3.2%)		0/392 (0%)
Pain in extremity	0/147 (0%)		0/149 (0%)		11/376 (2.9%)		0/392 (0%)
Nervous system disorders
Muscle spasticity	14/147 (9.5%)		15/149 (10.1%)		27/376 (7.2%)		0/392 (0%)
Headache	6/147 (4.1%)		4/149 (2.7%)		14/376 (3.7%)		0/392 (0%)
somnolence	0/147 (0%)		0/149 (0%)		21/376 (5.6%)		0/392 (0%)
multiple sclerosis relapse	0/147 (0%)		0/149 (0%)		12/376 (3.2%)		0/392 (0%)
dizziness	0/147 (0%)		0/149 (0%)		10/376 (2.7%)		1/392 (0.3%)
Tremor	0/147 (0%)		0/149 (0%)		6/376 (1.6%)		0/392 (0%)
Psychiatric disorders
Insomnia	0/147 (0%)		0/149 (0%)		9/376 (2.4%)		0/392 (0%)
Insomnia	1/147 (0.7%)		3/149 (2%)		9/376 (2.4%)		1/392 (0.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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