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Dysport® Adult Lower Limb Spasticity Study

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01249404
First Posted: November 29, 2010
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Ipsen
  Purpose
The purpose of this research study is to assess the efficacy of Dysport® compared to placebo in improving muscle tone in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury.

Condition Intervention Phase
Leg Spasticity Drug: Botulinum type A toxin (Dysport®) Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicentre, Double-blind, Prospective, Randomized, Placebo-controlled Study, Assessing the Efficacy and Safety of Dysport® Used for the Treatment of Lower-limb Spasticity in Adult Subjects With Hemiparesis Due to Stroke or Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) [ Time Frame: Baseline and Week 4 ]
    Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The mean change from baseline at Week 4 is reported.


Secondary Outcome Measures:
  • Physician's Global Assesment (PGA) of Treatment Response at Week 4 [ Time Frame: At Week 4 ]
    An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA score at Week 4 is reported.

  • Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed [ Time Frame: Baseline and Week 4 ]
    Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Week 4 is reported.


Other Outcome Measures:
  • Mean Change From Baseline in MAS Score in the GSC (Knee Extended) at Weeks 1 and 12 [ Time Frame: Baseline and Weeks 1 and 12 ]
    Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The mean change from baseline at Weeks 1 and 12 are reported.

  • Mean Change From Baseline in MAS Score in the Soleus (Knee Flexed) at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Muscle tone in the treated limb was assessed by MAS in the soleus (with the knee flexed) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • PGA of Treatment Response at Week 12 [ Time Frame: At Week 12 ]
    An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA scores at Week 12 are reported.

  • Mean Change From Baseline in Comfortable Barefoot Walking Speed at Weeks 1 and 12 [ Time Frame: Baseline and Weeks 1 and 12 ]
    Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1 and 12 are reported.

  • Mean Change From Baseline in Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and are reported.

  • Mean Change From Baseline in Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Maximal walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made with shoes, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Cadence With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Average Step Length With Comfortable Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Cadence With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Cadence was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported

  • Mean Change From Baseline in Average Step Length With Comfortable Barefoot Walking Speed at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Average step length was assessed during the 10-metre walking speed test at comfortable walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Cadence With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Cadence was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Average Step Length With Maximal Walking Speed With Shoes at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Average step length was assessed during the 10-metre walking speed test at maximal walking speed and with shoes. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Cadence With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Cadence was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Average Step Length With Maximal Barefoot Walking Speed at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Average step length was assessed during the 10-metre walking speed test at maximal walking speed and barefoot. The evaluator walked beside the subject during the test and counted the number of steps taken during the 10-metre walk. The gait parameters were measured at baseline, Weeks 1, 4 and 12, discretionary visits at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in the Tardieu Scale in the GSC (Knee Extended) at Weeks 1, 4 and 12: Spasticity Grade (Y) [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    The Tardieu Scale in the GSC was used to assess spasticity with the knee extended. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Angle of Arrest (XV1), Angle of Catch (XV3) and Spasticity Angle (X) [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. Assessments were made at slow (V1) and fast (V3) speeds of stretch. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest (XV1), either due to subject discomfort or a mechanical resistance. The same movement is repeated at a fast speed to determine the angle of catch and release (XV3). The spasticity angle (X) was calculated as the difference between XV1 and XV3. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in the Tardieu Scale in the Soleus (Knee Flexed) at Weeks 1, 4 and 12: Spasticity Grade (Y) [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    The Tardieu Scale in the soleus was used to assess spasticity with the knee flexed. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 = no resistance throughout passive movement; 1 = slight resistance throughout passive movement; 2 = clear catch at precise angle, interrupting passive movement, followed by release; 3 = fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release; 4 = unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. The Tardieu Scale ratings were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits if required at Weeks 16, 20 and 24 and at end of study. The mean change from baseline for spasticity grade at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in the Range of Active Dorsiflexion at Weeks 1, 4 and 12 (Knee Extended and Flexed) [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    Range of active dorsiflexion of the ankle joint, both with the knee flexed (90°) and extended (measured by goniometry) was used to assess treatment response. The measurements were made prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.

  • Mean Change From Baseline in Lower Limb Pain at Weeks 1, 4 and 12 [ Time Frame: Baseline and Weeks 1, 4 and 12 ]
    The intensity of lower limb pain was evaluated using the Scale of Pain Intensity (SPIN) which provided a pictorial representation of pain in a 6-point graphic scale with the degree of red shading inside a circle representing the intensity of pain. The bottom and top of the scale are anchored by two extremes: 'no pain' (circle with no red shading and scored as 0) and 'pain as bad as it could be' (circle completely red and scored as 5), marked with either verbal or visual cues. The intervening points are represented by red circles increasing proportionally in size. The subject marks the circle that best indicates their pain intensity. The SPIN assessments were obtained prior to the study treatment at baseline, and then after injection at Weeks 1, 4 and 12, and at discretionary visits when needed at Weeks 16, 20 and 24 and at end of study. The mean change from baseline at Weeks 1, 4 and 12 are reported.


Enrollment: 388
Study Start Date: March 2011
Study Completion Date: May 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dysport® 1000 U, IM
1000 U, I.M. (in the muscle), on day 1 (single treatment cycle)
Drug: Botulinum type A toxin (Dysport®)
I.M. injection on day 1 (single treatment cycle)
Other Name: AbobotulinumtoxinA (non-proprietary name)
Experimental: Dysport® 1500 U, IM
1500 U, I.M., on day 1 (single treatment cycle)
Drug: Botulinum type A toxin (Dysport®)
I.M. injection on day 1 (single treatment cycle)
Other Name: AbobotulinumtoxinA (non-proprietary name)
Placebo Comparator: Placebo
I.M., on day 1 (single treatment cycle)
Drug: Placebo
I.M. injection on day 1 (single treatment cycle)

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects aged 18 to 80 years of age
  • Post stroke or brain injury
  • Intensity of muscle tone greater than or equal to 2, as measured on the Modified Ashworth Scale
  • Ambulatory patients

Exclusion Criteria:

  • Fixed contractures
  • Physiotherapy initiated less than 4 weeks before entry
  • Previous surgery or previous treatment with phenol and/or alcohol in lower limb
  • Neurological/neuromuscular disorders which may interfere with protocol evaluations
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01249404


  Show 62 Study Locations
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Ipsen Study Director Ipsen
  More Information

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01249404     History of Changes
Other Study ID Numbers: Y-55-52120-140
2009-015868-34 ( EudraCT Number )
First Submitted: November 25, 2010
First Posted: November 29, 2010
Results First Submitted: July 3, 2017
Results First Posted: October 17, 2017
Last Update Posted: October 17, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Muscle Spasticity
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
abobotulinumtoxinA
Botulinum Toxins, Type A
onabotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents