IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Cervical Dystonia

Cervical Dystonia Clinical Trial

Official title:

Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Trial With a Double-blind Parallel-group Extension Period to Investigate the Efficacy and Safety of Different Doses of IncobotulinumtoxinA (Xeomin) in the Treatment of Cervical Dystonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00407030
• Other study ID #: MRZ 60201-0408
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2006
• Last updated: July 12, 2013
• Start date: July 2006
• Est. completion date: June 2009

Study information

• Verified date: July 2013
• Source: Merz Pharmaceuticals GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

At baseline patients received incobotulinumtoxinA (Xeomin) or placebo. Thereafter, all patients who entered the extension period were treated with up to five injection sessions of incobotulinumtoxinA (Xeomin) during the extension period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: June 2009
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Main Inclusion Criteria:

• Male or female outpatients between ages 18 and 75 years inclusive)

• A clinical diagnosis of cervical dystonia (i.e. spasmodic torticollis) with predominantly rotational form and a need for injection (determined by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total score)

• TWSTRS-Total score >= 20

• TWSTRS-Severity score >= 10

• TWSTRS-Disability score >= 3

• TWSTRS-Pain score >= 1

• On a stable dose of medications (if any) used for focal dystonia treatment (e.g. anticholinergics and benzodiazepines) for at least 3 months prior to and expected throughout the Main Period

• For pre-treated patients only: Source documentation of the last two consecutive injection sessions with Botulinum Toxin and stable therapeutic response directly prior to trial entry

• For pre-treated patients only: At least 10 weeks must have been passed between the last injection with Botulinum Toxin for cervical dystonia and baseline

• For pre-treated patients only: The most recent injection with Botulinum Toxin must have been maximal 300 Units of type A or 12,000 Units of type B

Main Exclusion Criteria:

• Traumatic torticollis or tardive torticollis

• TWSTRS-Severity score for anterocollis >= 2 points (pure anterocollis)

• TWSTRS-Severity score for retrocollis >= 2 points (pure retrocollis)

• Myotomy or denervation surgery in the affected muscles (e.g. peripheral denervation and/or spinal cord stimulation)

• Hypersensitivity to human serum albumin, sucrose, or Botulinum Toxin Type A

• Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the trial

• Current swallowing disorder of any origin (dysphagia scale >= 3, i.e. severe, with swallowing difficulties and requiring a change in diet)

• Marked limitation on passive range of motion that suggests contractures or other structural abnormality, e.g. cervical contractures or cervical spine syndrome

• Treatment with Botulinum Toxins for any indication other than cervical dystonia within 4 months prior to baseline and during the trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Drug:
• incobotulinumtoxinA (Xeomin) (240 Units)
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (240 Units)
• incobotulinumtoxinA (Xeomin) (120 Units)
incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (120 Units)
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merz Pharmaceuticals GmbH

Country where clinical trial is conducted

United States, 

References & Publications (2)

Comella CL, Jankovic J, Truong DD, Hanschmann A, Grafe S; U.S. XEOMIN Cervical Dystonia Study Group. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN®, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. — View Citation

Evidente VG, Fernandez HH, LeDoux MS, Brashear A, Grafe S, Hanschmann A, Comella CL. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. J Neural Transm (Vienna). 2013 Dec;120(12):1699-707. doi: 10.1007/s0070 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (240 Units) Versus Placebo	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.	Baseline, week 4	No
Primary	Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (120 Units) Versus Placebo	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.	Baseline, week 4	No
Primary	Change From Baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) -Total Score at Week 4 After Injection of the Main Period - Xeomin (240 Units) Versus Xeomin (120 Units)	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.	Baseline, week 4	No
Secondary	Change From Baseline in the TWSTRS-Total Score	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.	Baseline, week 8, final visit (up to 20 weeks after injection of the Main Period)	No
Secondary	Change From Baseline in the TWSTRS Disability Subscore	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.	Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period)	No
Secondary	Change From Baseline in the TWSTRS Severity Subscore	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.	Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period)	No
Secondary	Change From Baseline in the TWSTRS Pain Subscore	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.	Baseline, week 4, week 8, final visit (up to 20 weeks after injection of the Main Period)	No
Secondary	Patient Evaluation of Global Response (PEGR) at Final Visit	The PEGR is a descriptive subjective 9-point response scale ranging from "complete abolishment of signs and symptoms" (value=+4) down to "very marked worsening" (value=-4).	Final visit (up to 20 weeks after injection of the Main Period)	No