Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SUN13837 Injection in Adult Subjects With Acute Spinal Cord Injury (ASCI)

• ClinicalTrials.gov Identifier: NCT01502631
• Recruitment Status: Completed
• First Posted: January 2, 2012
• Results First Posted: January 15, 2021
• Last Update Posted: January 15, 2021
• Sponsor: Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Spinal Cord Injury
• Interventions: Drug: SUN13837 injection; Drug: Placebo
• Enrollment: 65

Participant Flow

Recruitment Details	A total of 65 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 19 clinic sites in the United States of America, 2 in France, 1 in the United Kingdom,1 in Spain, and 1 in the Czech Republic. Four (4) of the participants were not treated. The data on the 61 treated participants are presented in this report.
Pre-assignment Details	Participants with acute traumatic cervical spinal cord injury (ASCI) within 12 hours of treatment were enrolled in this study.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Period Title: Overall Study
Started	30	31
Completed	10	11
Not Completed	20	20
Reason Not Completed
Adverse Event	5	8
Lost to Follow-up	2	2
Participant withdrew consent	2	4
Participant non-compliant	1	0
Investigator's decision	0	1
Other	10	5

Baseline Characteristics

Arm/Group Title		SUN13837	Placebo	Total
Arm/Group Description		Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Total of all reporting groups
Overall Number of Baseline Participants		30	31	61
Baseline Analysis Population Description		Baseline characteristics were assessed in the Safety Population.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	30 participants	31 participants	61 participants
		37.9 (16.6)	38.8 (17.2)	38.4 (16.8)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	30 participants	31 participants	61 participants
< 55 years		25 83.3%	25 80.6%	50 82.0%
≥ 55 years		5 16.7%	6 19.4%	11 18.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	31 participants	61 participants
	Female	4 13.3%	5 16.1%	9 14.8%
	Male	26 86.7%	26 83.9%	52 85.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	31 participants	61 participants
	Hispanic or Latino	1 3.3%	2 6.5%	3 4.9%
	Not Hispanic or Latino	29 96.7%	26 83.9%	55 90.2%
	Unknown or Not Reported	0 0.0%	3 9.7%	3 4.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants	31 participants	61 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 6.7%	5 16.1%	7 11.5%
	Native Hawaiian or Other Pacific Islander	2 6.7%	1 3.2%	3 4.9%
	Black or African American	4 13.3%	5 16.1%	9 14.8%
	White	22 73.3%	17 54.8%	39 63.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	3 9.7%	3 4.9%

Outcome Measures

1. Primary Outcome

Title	Total Spinal Cord Independence Measure, Version III (SCIM III) Score Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury
Description	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains: Self-Care (6 items, scores range from 0 to 20), Respiration and Sphincter Management (4 items, scores range from 0 to 40), and Mobility (9 items, scores range from 0 to 40). The total SCIM score ranges from 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. An improvement of at least 4 points of the total SCIM showed a small significant improvement, and 10 points showed a substantial improvement.
Time Frame	Week 2, week 4, week 8 and week 16 post dose.

Outcome Measure Data

Analysis Population Description

Total Spinal Cord Independence Measure was assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Score on a scale
Week 2	15.87; (10.15 to 21.59)	10.26; (4.73 to 15.79)
Week 4	22.56; (15.65 to 29.47)	15.69; (8.87 to 22.51)
Week 8	28.77; (21.34 to 36.20)	25.74; (18.39 to 33.09)
Week 16	38.14; (30.14 to 46.14)	33.60; (25.67 to 41.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SUN13837, Placebo
	Comments	Difference (SUN13837 - Placebo) at Week 2
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2182
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean
	Estimated Value	5.61
	Confidence Interval	(2-Sided) 90%; -1.93 to 13.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.497
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SUN13837, Placebo
	Comments	Difference (SUN13837 - Placebo) at Week 4
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2260
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean
	Estimated Value	6.87
	Confidence Interval	(2-Sided) 90%; -2.54 to 16.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.583
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SUN13837, Placebo
	Comments	Difference (SUN13837 - Placebo) at Week 8
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6184
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean
	Estimated Value	3.03
	Confidence Interval	(2-Sided) 90%; -7.15 to 13.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.023
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SUN13837, Placebo
	Comments	Difference (SUN13837 - Placebo) at Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4912
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean
	Estimated Value	4.54
	Confidence Interval	(2-Sided) 90%; -6.48 to 15.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.524
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group
Description	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains: Self-Care (6 items, scores range from 0 to 20), Respiration and Sphincter Management (4 items, scores range from 0 to 40), and Mobility (9 items, scores range from 0 to 40). The total SCIM score ranges from 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. An improvement of at least 4 points of the total SCIM showed a small significant improvement, and 10 points showed a substantial improvement.
Time Frame	Week 16 post dose

Outcome Measure Data

Analysis Population Description

Sensitivity analyses were assessed in the Intent-to-Treat (ITT) and Efficacy Evaluable (EE) populations. The EE Population consisted of all subjects in the ITT Population who did not have any major protocol violations that impacted efficacy and were observed for efficacy for at least 2 SCIM III evaluations.

Arm/Group Title		SUN13837	Placebo
Arm/Group Description:		Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed		27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Score on a scale
Primary (EE)	Number Analyzed	24 participants	25 participants
		38.25; (30.96 to 45.54)	30.48; (23.41 to 37.55)
LOCF (ITT)	Number Analyzed	27 participants	28 participants
		36.12; (28.60 to 43.64)	30.84; (23.38 to 38.30)
Multiple Imputation (ITT)	Number Analyzed	27 participants	28 participants
		37.96; (29.32 to 46.61)	32.17; (23.46 to 40.88)
Simple Multiple Imputation (ITT)	Number Analyzed	27 participants	28 participants
		38.49; (30.06 to 46.93)	32.00; (23.63 to 40.38)

3. Secondary Outcome

Title	Change From Baseline of Total Motor Score (TMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury
Description	TMS was the sum of the overall Upper Extremity Motor Score (UEMS) and the overall Lower Extremity Motor Score (LEMS) of ISNCSCI. The score on the scale runs from a minimum value of 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. The UEMS was defined as the sum of the motor function scores in the cervical spinal segments C5, C6, C7, C8, and T1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score (with a maximum score of 50). The LEMS was defined as the sum of the motor function scores in the spinal segments lumbar level 2, lumbar level 3, lumbar level 4, lumbar level 5, and sacral level 1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score (with a maximum score of 50).
Time Frame	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.

Outcome Measure Data

Analysis Population Description

Total Motor Score (TMS) was assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Units on a scale
Day 3	5.84; (1.56 to 10.12)	1.20; (-2.95 to 5.35)
Week 2	8.66; (3.55 to 13.77)	4.04; (-0.89 to 8.97)
Week 4	11.96; (6.19 to 17.72)	6.35; (0.75 to 11.95)
Week 8	14.81; (8.06 to 21.57)	11.31; (4.69 to 17.93)
Week 16	16.58; (9.40 to 23.76)	14.07; (7.06 to 21.09)

4. Secondary Outcome

Title	Self-Care and Mobility Subscale Scores of Spinal Cord Independence Measure, Version III (SCIM III) Score Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury
Description	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains, two of which are Self-care and Mobility. The self-care domain is a subscale of 6 items and scores range from 0 to 20 (higher scores indicate a better outcome). The mobility domain consists of 9 items with subscale scores range from 0 to 40 (higher scores indicate a better outcome). The score for the combined Self-Care and Mobility subscale ranges from 0 - 60 points; higher scores indicate a better outcome
Time Frame	Week 2, Week 4, Week 8, and Week 16 post dose.

Outcome Measure Data

Analysis Population Description

Self-Care and Mobility Subscale Scores were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Score on a scale
Week 2	5.76; (2.05 to 9.47)	3.77; (0.18 to 7.35)
Week 4	9.18; (4.81 to 13.56)	6.45; (2.14 to 10.77)
Week 8	14.70; (9.87 to 19.53)	11.25; (6.47 to 16.03)
Week 16	18.73; (13.43 to 24.03)	15.02; (9.77 to 20.27)

5. Secondary Outcome

Title	Upper Extremity Motor Scores (UEMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord
Description	The UEMS was defined as the sum of the motor function scores in the cervical spinal segments C5, C6, C7, C8, and T1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and an overall score of 0-50 with a maximum score of 50. A higher score indicates a better outcome.
Time Frame	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.

Outcome Measure Data

Analysis Population Description

Upper Extremity Motor Scores (UEMS) were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Units on a scale
Day 3	2.08; (-0.14 to 4.31)	-1.24; (-3.45 to 0.98)
Week 2	3.98; (1.50 to 6.46)	0.59; (-1.83 to 3.02)
Week 4	5.95; (3.40 to 8.50)	1.73; (-0.79 to 4.24)
Week 8	8.66; (5.94 to 11.38)	3.83; (1.12 to 6.54)
Week 16	9.92; (7.10 to 12.74)	4.95; (2.17 to 7.73)

6. Secondary Outcome

Title	Lower Extremity Motor Scores (LEMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury
Description	The LEMS was defined as the sum of the motor function scores in the spinal segments lumbar level 2, lumbar level 3, lumbar level 4, lumbar level 5, and sacral level 1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score with a maximum score of 50. A higher score indicates a better outcome.
Time Frame	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.

Outcome Measure Data

Analysis Population Description

Lower Extremity Motor Scores (LEMS) were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	27	28
Least Squares Mean (90% Confidence Interval); Unit of Measure: Units on a scale
Day 3	2.71; (0.15 to 5.28)	3.22; (0.75 to 5.68)
Week 2	3.66; (0.94 to 6.38)	4.28; (1.67 to 6.88)
Week 4	4.89; (1.82 to 7.96)	5.36; (2.41 to 8.31)
Week 8	5.08; (1.22 to 8.94)	8.30; (4.53 to 12.08)
Week 16	6.13; (1.80 to 10.46)	9.96; (5.73 to 14.20)

7. Secondary Outcome

Title	Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury
Description	The protocol defined an adverse event (AE) as any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	Baseline up to approximately Day 182 post dose.

Outcome Measure Data

Analysis Population Description

The safety population was used to assess adverse events.

Arm/Group Title	SUN13837	Placebo
Arm/Group Description:	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
Overall Number of Participants Analyzed	30	31
Measure Type: Count of Participants; Unit of Measure: Participants
Urinary tract infection	21 70.0%	23 74.2%
Pyrexia	17 56.7%	14 45.2%
Decubitus ulcer	13 43.3%	13 41.9%
Insomnia	14 46.7%	12 38.7%
Pneumonia	9 30.0%	17 54.8%
Nausea	12 40.0%	10 32.3%
Muscle spasticity	12 40.0%	9 29.0%
Neuralgia	13 43.3%	8 25.8%
Anxiety	9 30.0%	10 32.3%
Constipation	7 23.3%	11 35.5%
Leukocytosis	8 26.7%	10 32.3%
Depression	8 26.7%	9 29.0%
Musculoskeletal pain	10 33.3%	7 22.6%
Orthostatic hypotension	9 30.0%	8 25.8%
Anaemia	5 16.7%	11 35.5%
Respiratory failure	8 26.7%	7 22.6%
Muscle spasms	8 26.7%	6 19.4%
Headache	9 30.0%	4 12.9%
Rash	9 30.0%	4 12.9%
Blood creatine phosphokinase increased	7 23.3%	5 16.1%

Adverse Events

Time Frame	Baseline up to approximately Day 182 post dose.
Adverse Event Reporting Description	The protocol defined an adverse event (AE) as any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Serious AEs are summarized across the on-treatment and off-treatment periods by descending order in the SUN13837 group.
Arm/Group Title	SUN13837	Placebo
Arm/Group Description	Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).	Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day [dosing to 27 days] in certain participants).
All-Cause Mortality
	SUN13837	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/30 (6.67%)	2/31 (6.45%)
Serious Adverse Events
	SUN13837	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	21/30 (70.00%)	23/31 (74.19%)
Blood and lymphatic system disorders
Anaemia † 1	5/30 (16.67%)	11/31 (35.48%)
Cardiac disorders
Arrhythmia † 1	1/30 (3.33%)	0/31 (0.00%)
Bradycardia † 1	1/30 (3.33%)	2/31 (6.45%)
Cardiac arrest † 1	1/30 (3.33%)	1/31 (3.23%)
Endocrine disorders
Thyroiditis † 1	1/30 (3.33%)	0/31 (0.00%)
Gastrointestinal disorders
Gastrointestinal haemorrhage † 1	1/30 (3.33%)	0/31 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/30 (0.00%)	1/31 (3.23%)
Nausea † 1	12/30 (40.00%)	10/31 (32.26%)
Constipation † 1	7/30 (23.33%)	11/31 (35.48%)
General disorders
Chest pain † 1	1/30 (3.33%)	0/31 (0.00%)
Euthanasia † 1	0/30 (0.00%)	1/31 (3.23%)
Hepatobiliary disorders
Cholecystitis † 1	0/30 (0.00%)	1/31 (3.23%)
Infections and infestations
Escherichia urinary tract infection † 1	0/30 (0.00%)	1/31 (3.23%)
Lower respiratory tract infection † 1	0/30 (0.00%)	1/31 (3.23%)
Lung infection pseudomonal † 1	1/30 (3.33%)	0/31 (0.00%)
Pneumonia † 1	3/30 (10.00%)	1/31 (3.23%)
Pneumonia streptococcal † 1	0/30 (0.00%)	1/31 (3.23%)
Sepsis † 1	1/30 (3.33%)	0/31 (0.00%)
Urinary tract infection † 1	21/30 (70.00%)	23/31 (74.19%)
Urinary tract infection fungal † 1	0/30 (0.00%)	1/31 (3.23%)
Pneumonia † 1	9/30 (30.00%)	17/31 (54.84%)
Investigations
Electrocardiogram QT prolonged † 1	1/30 (3.33%)	1/31 (3.23%)
Hepatic enzyme increased † 1	2/30 (6.67%)	1/31 (3.23%)
Musculoskeletal and connective tissue disorders
Muscle spasms † 1	8/30 (26.67%)	6/31 (19.35%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma † 1	0/30 (0.00%)	1/31 (3.23%)
Nervous system disorders
Convulsion † 1	0/30 (0.00%)	1/31 (3.23%)
Ischaemic stroke † 1	0/30 (0.00%)	1/31 (3.23%)
Presyncope † 1	0/30 (0.00%)	1/31 (3.23%)
Muscle spasticity † 1	12/30 (40.00%)	9/31 (29.03%)
Neuralgia † 1	13/30 (43.33%)	8/31 (25.81%)
Headache † 1	9/30 (30.00%)	4/31 (12.90%)
Psychiatric disorders
Insomnia † 1	14/30 (46.67%)	12/31 (38.71%)
Anxiety † 1	9/30 (30.00%)	10/31 (32.26%)
Renal and urinary disorders
Anuria † 1	1/30 (3.33%)	0/31 (0.00%)
Pyuria † 1	0/30 (0.00%)	1/31 (3.23%)
Renal failure acute † 1	1/30 (3.33%)	1/31 (3.23%)
Urine abnormality † 1	0/30 (0.00%)	1/31 (3.23%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/30 (0.00%)	1/31 (3.23%)
Hypercapnia † 1	1/30 (3.33%)	0/31 (0.00%)
Hypoxia † 1	1/30 (3.33%)	0/31 (0.00%)
Pleural effusion † 1	1/30 (3.33%)	1/31 (3.23%)
Pneumonia aspiration † 1	1/30 (3.33%)	0/31 (0.00%)
Pulmonary embolism † 1	3/30 (10.00%)	0/31 (0.00%)
Respiratory distress † 1	1/30 (3.33%)	0/31 (0.00%)
Respiratory failure † 1	8/30 (26.67%)	7/31 (22.58%)
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	13/30 (43.33%)	13/31 (41.94%)
Rash † 1	9/30 (30.00%)	4/31 (12.90%)
Surgical and medical procedures
Withdrawal of life support † 1	0/30 (0.00%)	1/31 (3.23%)
Vascular disorders
Deep vein thrombosis † 1	1/30 (3.33%)	1/31 (3.23%)
Hypotension † 1	0/30 (0.00%)	1/31 (3.23%)
Orthostatic hypotension † 1	9/30 (30.00%)	8/31 (25.81%)
1 Term from vocabulary, MedDRA (15.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	SUN13837	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/30 (46.67%)	20/31 (64.52%)
Blood and lymphatic system disorders
Anaemia † 1	1/30 (3.33%)	0/31 (0.00%)
Leukocytosis † 1	0/30 (0.00%)	1/31 (3.23%)
Cardiac disorders
Arrhythmia † 1	1/30 (3.33%)	0/31 (0.00%)
Cardiac arrest † 1	1/30 (3.33%)	1/31 (3.23%)
Bradycardia † 1	0/30 (0.00%)	1/31 (3.23%)
Gastrointestinal disorders
Gastrointestinal haemorrhage † 1	1/30 (3.33%)	0/31 (0.00%)
Duodenal ulcer † 1	1/30 (3.33%)	0/31 (0.00%)
Neurogenic bowel † 1	1/30 (3.33%)	0/31 (0.00%)
Abdominal pain upper † 1	0/30 (0.00%)	1/31 (3.23%)
Dysphagia † 1	0/30 (0.00%)	1/31 (3.23%)
General disorders
Pyrexia † 1	2/30 (6.67%)	1/31 (3.23%)
Pain † 1	1/30 (3.33%)	0/31 (0.00%)
Euthanasia † 1	0/30 (0.00%)	1/31 (3.23%)
Hepatobiliary disorders
Cholecystitis † 1	0/30 (0.00%)	1/31 (3.23%)
Infections and infestations
Sepsis † 1	1/30 (3.33%)	0/31 (0.00%)
Investigations
Blood creatine phosphokinase increased † 1	2/30 (6.67%)	1/31 (3.23%)
C-reactive protein increased † 1	1/30 (3.33%)	0/31 (0.00%)
Alanin aminotransferase increased † 1	0/30 (0.00%)	1/31 (3.23%)
Aspartate aminotransferase increase † 1	0/30 (0.00%)	1/31 (3.23%)
Hepatic enzyme increased † 1	0/30 (0.00%)	1/31 (3.23%)
Metabolism and nutrition disorders
Hyponatraemia † 1	1/30 (3.33%)	0/31 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain † 1	1/30 (3.33%)	1/31 (3.23%)
Neck pain † 1	1/30 (3.33%)	0/31 (0.00%)
Extremity contracture † 1	0/30 (0.00%)	1/31 (3.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma † 1	0/30 (0.00%)	1/31 (3.23%)
Nervous system disorders
Neurogenic bladder † 1	2/30 (6.67%)	0/31 (0.00%)
Pseudomeningocele † 1	1/30 (3.33%)	0/31 (0.00%)
Ischaemic stroke † 1	0/30 (0.00%)	1/31 (3.23%)
Presyncope † 1	0/30 (0.00%)	1/31 (3.23%)
Spinal cord compression † 1	0/30 (0.00%)	1/31 (3.23%)
Spinal cord oedema † 1	0/30 (0.00%)	1/31 (3.23%)
Psychiatric disorders
Confusional state † 1	1/30 (3.33%)	0/31 (0.00%)
Depression † 1	0/30 (0.00%)	1/31 (3.23%)
Renal and urinary disorders
Anuria † 1	1/30 (3.33%)	0/31 (0.00%)
Renal failure acute † 1	1/30 (3.33%)	0/31 (0.00%)
Urinary tract infection † 1	0/30 (0.00%)	3/31 (9.68%)
Autonomic dysreflexia † 1	0/30 (0.00%)	2/31 (6.45%)
Urinary retention † 1	0/30 (0.00%)	1/31 (3.23%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1	4/30 (13.33%)	3/31 (9.68%)
Pulmonary embolism † 1	2/30 (6.67%)	0/31 (0.00%)
Atelectasis † 1	1/30 (3.33%)	2/31 (6.45%)
Dyspnoea † 1	1/30 (3.33%)	1/31 (3.23%)
Hypercapnia † 1	1/30 (3.33%)	0/31 (0.00%)
Pleural effusion † 1	1/30 (3.33%)	0/31 (0.00%)
Pneumonia aspiration † 1	1/30 (3.33%)	0/31 (0.00%)
Respiratory distress † 1	1/30 (3.33%)	0/31 (0.00%)
Tachypnoea † 1	1/30 (3.33%)	0/31 (0.00%)
Lower respiratory tract infection † 1	0/30 (0.00%)	1/31 (3.23%)
Acute respiratory failure † 1	0/30 (0.00%)	1/31 (3.23%)
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	1/30 (3.33%)	1/31 (3.23%)
Skin ulcer † 1	1/30 (3.33%)	1/31 (3.23%)
Pruritus † 1	0/30 (0.00%)	1/31 (3.23%)
Osteosynthesis † 1	0/30 (0.00%)	1/31 (3.23%)
Surgical and medical procedures
Withdrawal of life support † 1	0/30 (0.00%)	1/31 (3.23%)
Vascular disorders
Deep vein thrombosis † 1	0/30 (0.00%)	1/31 (3.23%)
Hypotension † 1	0/30 (0.00%)	1/31 (3.23%)
1 Term from vocabulary, MedDRA (15.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo
• Phone: 908-992-6400
• EMail: CTRinfo@dsi.com

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01502631
• Other Study ID Numbers: ASBI 603
• First Submitted: December 27, 2011
• First Posted: January 2, 2012
• Results First Submitted: December 10, 2020
• Results First Posted: January 15, 2021
• Last Update Posted: January 15, 2021