Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Spasticity in the Leg After a Stroke (PLUS)

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Post-stroke Spasticity of the Lower Limb
Interventions:	Drug: IncobotulinumtoxinA (400 Units); Drug: Placebo Comparator

  Participant Flow

  Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 331 individuals suffering from post-stroke lower-limb spasticity were screened and 290 were included in study at 51 sites. One ineligible subject was randomized to placebo but withdrawn from study prior to first treatment with study medication. For purpose of study analysis overall number of subjects enrolled is therefore considered 289.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 290 subjects were enrolled in study. One ineligible subject was randomized to placebo but withdrawn from study prior to first treatment with study medication. A total of 289 subjects were enrolled in main period. All of the 269 subjects who completed the main period of the study entered the open-label extension period.

Reporting Groups

	Description
IncobotulinumtoxinA (Xeomin) 400 Units	IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA (400 Units): Main period: One injection session of solution, prepared by reconstitution of powder with 0.9 percent (%) Sodium Chloride (NaCl), 400 units, total volume 8.0 milliliter (mL); Mode of administration: intramuscular injection. IncobotulinumtoxinA (400 Units): Open-Label Extension Period: All subjects receive three injection sessions of solution, prepared by reconstitution of powder with 0.9% NaCl, 400 units, total volume 8.0 mL; Mode of administration: intramuscular injection.
Placebo	Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection. Placebo Comparator: Main period: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding total placebo volume 8.0 mL; Mode of administration: intramuscular injection

Participant Flow for 2 periods

Period 1:   Main Period

	IncobotulinumtoxinA (Xeomin) 400 Units	Placebo
STARTED	144	145
Treated	144	145
COMPLETED	129	140
NOT COMPLETED	15	5
Death	0	1
Adverse Event	6	1
Lack of Efficacy	2	0
Withdrawal by Subject	5	2
Predefined discontinuation criteria	2	1

Period 2:   Open-Label Extension Period

	IncobotulinumtoxinA (Xeomin) 400 Units	Placebo
STARTED	269	0
Treated	269	0
COMPLETED	218	0
NOT COMPLETED	51	0
Adverse Event	15	0
Withdrawal by Subject	14	0
Lack of Efficacy	5	0
Death	1	0
Lost to Follow-up	1	0
Non-compliance	9	0
Predefined discontinuation criteria	6	0

  Baseline Characteristics

  Hide Baseline Characteristics

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.
The Safety Evaluation Set (SES) is the subset of all subjects who were exposed to Investigational product (IP) in the main period at least once.

Reporting Groups

	Description
Main Period: IncobotulinumtoxinA (Xeomin) 400 Units	IncobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection. IncobotulinumtoxinA (400 Units): Main period: One injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), 400 units, total volume 8.0 mL; Mode of administration: intramuscular injection.
Main Period: Placebo	Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection. Placebo Comparator: Main period: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding total placebo volume 8.0 mL; Mode of administration: intramuscular injection
Total	Total of all reporting groups

Baseline Measures

	Main Period: IncobotulinumtoxinA (Xeomin) 400 Units	Main Period: Placebo	Total
Overall Participants Analyzed; [Units: Participants]	144	145	289
Age; [Units: Years]; Mean (Standard Deviation)	57.3 (11.2)	57.0 (13.0)	57.2 (12.1)
Gender; [Units: Participants]; Count of Participants
Female	40 27.8%	55 37.9%	95 32.9%
Male	104 72.2%	90 62.1%	194 67.1%

  Outcome Measures

  Show All Outcome Measures

1. Primary:

Change From Baseline in Ashworth Scale (AS) for Plantar Flexors at Week 4 [ Time Frame: Baseline and Week 4 ]

  Show Outcome Measure 1

2. Primary:

Co-primary Variable: Investigator's Global Assessment of Efficacy at Week 12 [ Time Frame: Baseline to Week 12 ]

  Show Outcome Measure 2

3. Secondary:

Response Rate for Plantar Flexors at All Post-Baseline Visits for Subjects With an Improvement (Reduction) of at Least 1 Point From Baseline in the Ashworth Scale (AS) [ Time Frame: Week 4, 8, and 12 ]

  Show Outcome Measure 3

4. Secondary:

Ashworth Scale (AS) for Plantar Flexors at All Post-Baseline Visits [ Time Frame: Baseline, Week 4, 8, and 12 ]

  Show Outcome Measure 4

  Serious Adverse Events

  Show Serious Adverse Events

  Other Adverse Events

  Show Other Adverse Events

  Limitations and Caveats

  Hide Limitations and Caveats

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
No text entered.

  More Information

  Hide More Information

Certain Agreements:  

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

There IS 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.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the Investigator will consider these doubts in the publication as long as the scientific neutrality is not affected.

Results Point of Contact:  

Name/Title: Public Disclosure Manager
Organization: Merz Pharmaceuticals GmbH
phone: +49 69 1503 1
e-mail: clinicaltrials@merz.de

Responsible Party:	Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:	NCT01464307 History of Changes
Other Study ID Numbers:	MRZ 60201/SP/3002; 2010-024579-23 ( EudraCT Number )
First Submitted:	November 1, 2011
First Posted:	November 3, 2011
Results First Submitted:	July 26, 2016
Results First Posted:	November 7, 2016
Last Update Posted:	November 7, 2016