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Randomized, Double-Blind, Placebo-Controlled, Parallel, Group Dose-Response, Study of E2014 in Patients WIth Spasmodic Torticollis

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ClinicalTrials.gov Identifier: NCT00165776
Recruitment Status : Completed
First Posted : September 14, 2005
Results First Posted : January 8, 2014
Last Update Posted : March 10, 2014
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Conditions Cervical Dystonia
Spasmodic Torticollis
Intervention Drug: BOTULINUM TOXIN TYPE B
Enrollment 133
Recruitment Details 130 patients (33 of the placebo group, 34 of the 2500U group, 32 of the 5000U group, and 31 of the 10000U group) received study treatment, but after randomization, 3 patients (2 of the placebo group and 1 of the 5000U group) had no treatment. The reason was that 2 of them requested withdrawal from the study and 1 ceased to return for visits.
Pre-assignment Details  
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose 2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose 5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose 10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Period Title: Overall Study
Started 35 34 33 31
Completed 31 33 31 29
Not Completed 4 1 2 2
Reason Not Completed
Lack of Efficacy             0             0             0             1
Withdrawal by Subject             4             1             2             0
Worsening of Cervical Dystonia             0             0             0             1
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U Total
Hide Arm/Group Description placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose. Two subjects from the placebo group did not receive treatment after randomization. 2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose 5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose. One subject from the 5,000 U/2 mL did not receive treatment after randomization. 10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose Total of all reporting groups
Overall Number of Baseline Participants 33 34 32 31 130
Hide Baseline Analysis Population Description
After randomized to the treatment groups, 3 patients (2 of the placebo group and 1 of the 5000U group) had no treatment. The reason was that 2 of them requested withdrawal from the study and 1 ceased to return for visits.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 32 participants 31 participants 130 participants
Less than 40 years 10 11 10 8 39
40 to less than 60 years 12 8 18 13 51
Greater than or equal to 60 years 11 15 4 10 40
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 32 participants 31 participants 130 participants
Female
12
  36.4%
11
  32.4%
15
  46.9%
14
  45.2%
52
  40.0%
Male
21
  63.6%
23
  67.6%
17
  53.1%
17
  54.8%
78
  60.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Japanese Number Analyzed 33 participants 34 participants 32 participants 31 participants 130 participants
33 34 32 31 130
1.Primary Outcome
Title Mean Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Treatment
Hide Description

The TWSTRS-Total score is the sum of scores of the three components of the scale:

  • TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity)
  • TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain)
  • TWSTRS-Disability score which ranges from 0 (=no disability) to 30 (=maximum disability).

The TWSTRS total score ranges from 0 (=best value) to 85 (=worst value). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.

Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population: All subjects who received study treatment
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Points on a Scale
3  (1.3) 8.9  (1.8) 7.6  (1.6) 10.5  (1.6)
2.Secondary Outcome
Title Mean Change From Baseline in Patient Global Assessment - Visual Analog Scale (PtGA-VAS) at Week 4 After Treatment
Hide Description Change from Baseline in PtGA-VAS is computed as Week 4 value minus baseline value. A negative value in change from baseline indicates an improvement. Participants answered: "Considering all the ways your cervical dystonia affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Millimeters
-0.4  (3.2) 11.9  (2.6) 9.9  (3) 13.3  (3)
3.Secondary Outcome
Title Mean Change From Baseline in Physician Global Assessment Disease Assessment - Visual Analog Scale (PGA-VAS) at Week 4 After Treatment
Hide Description Change from Baseline in PGA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 4 value minus baseline value. A negative value in change from baseline indicates an improvement.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Millimeters
2  (2.2) 10.6  (2.9) 11.2  (2.6) 16.9  (2.8)
4.Secondary Outcome
Title Mean Change From Baseline in the TWSTRS - Functional Disability Score at Week 4 After Treatment
Hide Description TWSTRS-Disability score which ranges from 0 (=no disability)to 30 (=maximum disability). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Points on a Scale
0.6  (0.7) 2.5  (0.6) 1.9  (0.8) 3.1  (0.5)
5.Secondary Outcome
Title Mean Change From Baseline in the TWSTRS - Pain Score at Week 4 After Treatment
Hide Description TWSTRS-Pain score which ranges from 0 (=no pain) to 20 (=maximum pain). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Points on a Scale
0.8  (0.4) 2.9  (0.7) 2  (0.7) 2.7  (0.7)
6.Secondary Outcome
Title Mean Change From Baseline in the TWSTRS - Severity Score at Week 4 After Treatment
Hide Description TWSTRS-Severity score which ranges from 0 (=absence of severity) to 35 points (=maximum severity). The change from baseline was calculated as the score at the corresponding visit minus the baseline score.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Points on a Scale
1.6  (0.6) 3.5  (0.8) 3.7  (0.7) 4.7  (0.8)
7.Secondary Outcome
Title Mean Change From Baseline in Patient Pain Assessment (VAS) at Week 4 After Treatment
Hide Description Change from Baseline in Patient's Pain Assessment-VAS is computed as Week 4 value minus baseline value. A negative value in change from baseline indicates an improvement. The patient's assessment of pain was performed using a 100 mm VAS)ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.
Time Frame Baseline, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description:
placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose
2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose
5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
Overall Number of Participants Analyzed 33 34 32 31
Mean (Standard Error)
Unit of Measure: Millimeters
-6.6  (4.1) -15  (4.5) -13.4  (4.7) -8.7  (4.4)
Time Frame Baseline to last observation carried forward
Adverse Event Reporting Description 130 patients (33 of the placebo group, 34 of the 2500U group, 32 of the 5000U group, and 31 of the 10000U group) received study treatment, but after randomization, 3 patients (2 of the placebo group and 1 of the 5000U group) had no treatment. The reason was that 2 of them requested withdrawal from the study and 1 ceased to return for visits.
 
Arm/Group Title Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Hide Arm/Group Description placebo/ 2 mL was intramuscularly injected to cervical muscles as a single dose 2,500 U/2 mL was intramuscularly injected to cervical muscles as a single dose 5,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose 10,000 U/2 mL was intramuscularly injected to cervical muscles as a single dose
All-Cause Mortality
Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/33 (0.00%)      0/34 (0.00%)      0/32 (0.00%)      2/31 (6.45%)    
Eye disorders         
Cataract  1  0/33 (0.00%)  0 0/34 (0.00%)  0 0/32 (0.00%)  0 1/31 (3.23%)  1
Injury, poisoning and procedural complications         
Pelvic Fracture  1  0/33 (0.00%)  0 0/34 (0.00%)  0 0/32 (0.00%)  0 1/31 (3.23%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo E2014 2,500 U E2014 5,000 U E2014 10,000 U
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/33 (27.27%)      3/34 (8.82%)      4/32 (12.50%)      7/31 (22.58%)    
Gastrointestinal disorders         
Dysphagia  1  0/33 (0.00%)  1/34 (2.94%)  3/32 (9.38%)  7/31 (22.58%) 
Dry Mouth  1  0/33 (0.00%)  0/34 (0.00%)  0/32 (0.00%)  4/31 (12.90%) 
General disorders         
Thirst  1  1/33 (3.03%)  1/34 (2.94%)  1/32 (3.13%)  6/31 (19.35%) 
Injection Site Pain  1  2/33 (6.06%)  0/34 (0.00%)  2/32 (6.25%)  1/31 (3.23%) 
Infections and infestations         
Nasopharyngitis  1  9/33 (27.27%)  2/34 (5.88%)  4/32 (12.50%)  6/31 (19.35%) 
Investigations         
Blood Creatine Phosphokinase Increased  1  1/33 (3.03%)  2/34 (5.88%)  0/32 (0.00%)  2/31 (6.45%) 
Glucose Urine Present  1  0/33 (0.00%)  1/34 (2.94%)  1/32 (3.13%)  2/31 (6.45%) 
Nervous system disorders         
Headache  1  1/33 (3.03%)  1/34 (2.94%)  1/32 (3.13%)  3/31 (9.68%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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: Hiroki Shimizu, Study Director
Organization: Eisai Co., Ltd.
Phone: +81-3-3817-5245
Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier: NCT00165776     History of Changes
Other Study ID Numbers: E2014-J081-131
First Submitted: September 12, 2005
First Posted: September 14, 2005
Results First Submitted: July 12, 2013
Results First Posted: January 8, 2014
Last Update Posted: March 10, 2014