Dysport® Adult Upper Limb Spasticity Extension Study

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was designed as a multicentre study and included a total of 34 investigational sites in Belgium, the Czech Republic, France, Hungary, Italy, Poland, Russia, Slovakia and the United States of America (US) that included at least one subject. This study was an open label extension to the double blind Study 145 (Y-52-52120-145).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 227 subjects who completed Study 145, 4 subjects entered an observational phase and never received treatment with Dysport® in this open label extension study (Study 148). The remaining 223 subjects were eligible for retreatment and progressed to Study 148. In addition, 31 of the 34 de novo subjects screened were included in this study.

Reporting Groups

Description

Total Dysport®

A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m.) injections of Dysport® according to their individual needs, for a period of up to 12 months. All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject’s safety and efficacy response. From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.

Participant Flow:   Overall Study

	Total Dysport®
STARTED	258
Cycle 1	254
Cycle 2	229
Cycle 3	175
Cycle 4	81
Cycle 5	11
COMPLETED	222
NOT COMPLETED	36
Adverse Event	5
Withdrawal by Subject	18
Lack of Efficacy	3
Investigator Decision	1
Observational Phase	1
Subject Withdrawn Early in Error	4
Did Not Receive Treatment with Dysport®	4

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline characteristics are reported for the 254 Subjects who entered this open label study (223 from Study 145 and 31 de novo subjects) and received at least one open label injection of Dysport®.

Reporting Groups

Description

Total Dysport®

A total of 254 subjects in the open label study received between 1 and 5 i.m. injections of Dysport® according to their individual needs, for a period of up to 12 months. All subjects were administered an appropriate dosage of Dysport® (1000 U or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject’s safety and efficacy response. From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.

Baseline Measures

	Total Dysport®
Overall Participants Analyzed  [Units: Participants]	254
Age  [Units: Participants] Count of Participants
<=18 years	0   0.0%
Between 18 and 65 years	201  79.1%
>=65 years	53  20.9%
Age  [Units: Years] Mean (Standard Deviation)	52.4  (14)
Sex: Female, Male  [Units: Participants] Count of Participants
Female	91  35.8%
Male	163  64.2%
Ethnicity (NIH/OMB)  [Units: Participants] Count of Participants
Hispanic or Latino	16   6.3%
Not Hispanic or Latino	238  93.7%
Unknown or Not Reported	0   0.0%
Race (NIH/OMB)  [Units: Participants] Count of Participants
American Indian or Alaska Native	0   0.0%
Asian	7   2.8%
Native Hawaiian or Other Pacific Islander	0   0.0%
Black or African American	27  10.6%
White	218  85.8%
More than one race	2   0.8%
Unknown or Not Reported	0   0.0%

1.  Primary:

Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)   [ Time Frame: Up to Week 52 ]

2.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)   [ Time Frame: Up to Week 52 ]

3.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Heart Rate (HR)   [ Time Frame: Up to Week 52 ]

4.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Red Blood Cell (RBC) Count   [ Time Frame: Up to Week 52 ]

5.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)   [ Time Frame: Up to Week 52 ]

6.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Haematocrit   [ Time Frame: Up to Week 52 ]

7.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Haemoglobin (MCH)   [ Time Frame: Up to Week 52 ]

8.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Volume (MCV)   [ Time Frame: Up to Week 52 ]

9.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets   [ Time Frame: Up to Week 52 ]

10.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)   [ Time Frame: Up to Week 52 ]

11.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)   [ Time Frame: Up to Week 52 ]

12.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine   [ Time Frame: Up to Week 52 ]

13.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose   [ Time Frame: Up to Week 52 ]

14.  Primary:

Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR   [ Time Frame: Up to Week 52 ]

15.  Primary:

Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies   [ Time Frame: Up to Week 52 ]

16.  Secondary:

Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4   [ Time Frame: At Week 4 ]

17.  Secondary:

Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG   [ Time Frame: At Week 4 ]

18.  Secondary:

Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4   [ Time Frame: At Week 4 ]

19.  Secondary:

Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4   [ Time Frame: At Week 4 ]

20.  Secondary:

Mean Change From Baseline MAS in the Wrist Flexors at Week 4   [ Time Frame: At Week 4 ]

21.  Secondary:

Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4   [ Time Frame: At Week 4 ]

22.  Secondary:

Mean Change From Baseline MAS in the Elbow Flexors at Week 4   [ Time Frame: At Week 4 ]

23.  Secondary:

Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4   [ Time Frame: At Week 4 ]

24.  Secondary:

Mean Change From Baseline MAS in the Shoulder Extensors at Week 4   [ Time Frame: At Week 4 ]

25.  Secondary:

Physician's Global Assessment (PGA) of Treatment Response at Week 4   [ Time Frame: At Week 4 ]

26.  Secondary:

Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4   [ Time Frame: At Week 4 ]

27.  Secondary:

Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4   [ Time Frame: At Week 4 ]

28.  Secondary:

Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4   [ Time Frame: At Week 4 ]

29.  Secondary:

Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG   [ Time Frame: At Week 4 ]

30.  Secondary:

Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG   [ Time Frame: At Week 4 ]

31.  Secondary:

Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG   [ Time Frame: At Week 4 ]

32.  Secondary:

Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG   [ Time Frame: At Week 4 ]

33.  Secondary:

Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG   [ Time Frame: At Week 4 ]

34.  Secondary:

Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG   [ Time Frame: At Week 4 ]

35.  Secondary:

Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors   [ Time Frame: At Week 4 ]

36.  Secondary:

Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors   [ Time Frame: At Week 4 ]

37.  Secondary:

Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs   [ Time Frame: At Week 4 ]

38.  Secondary:

Mean Change From Baseline at Week 4 in Ease of Applying a Splint   [ Time Frame: At Week 4 ]

39.  Secondary:

Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4   [ Time Frame: At Week 4 ]

40.  Secondary:

Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit   [ Time Frame: Up to Week 52 ]

41.  Secondary:

Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit   [ Time Frame: Up to Week 52 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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