Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus - Full Text View

Purpose

Primary objective is to evaluate the efficacy of single-dose treatment with GSK1358820 compared with non-treatment in patients with strabismus based on angles of strabismus in the primary position.

Condition	Intervention	Phase
Strabismus	Drug: GSK1358820	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Evaluator-masked, Parallel-group, Non-treatment-controlled Study Followed by an Open-label Study to Evaluate Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus

Resource links provided by NLM:

MedlinePlus related topics: Botox

Drug Information available for: OnabotulinumtoxinA

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Change from baseline in strabismus angle (PD; Prism Diopter) of primary position at Week 4 of the first treatment period [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle

Secondary Outcome Measures:

Change from baseline in strabismus angle (PD) in the primary position at Weeks 1 and 2 after the initial injection of the first treatment period [ Time Frame: Weeks 1 and 2 after the initial injection of the first treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Change from baseline in angle (PD) in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the final injection of the first treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 (before reinjection of the second treatment period if applicable) after the final injection of the first treatment period (after randomization in the non-treatment group) ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Change from baseline in strabismus angle (PD) in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Absolute strabismus angle (PD) in the primary position at Weeks 1, 2 and 4 of the first treatment period [ Time Frame: Weeks 1, 2 and 4 of the first treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Absolute strabismus angle (PD) in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the first treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 (before reinjection of the second treatment period if applicable) after the final injection of the first treatment period(after randomization in the non-treatment group) ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Absolute strabismus angle (PD) in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Percent change from baseline in strabismus angle in the primary position at Weeks 1, 2 and 4 of the first treatment period [ Time Frame: Weeks 1, 2 and 4 of the first treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Percent change from baseline in strabismus angle in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the first treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 (before reinjection of the second treatment period if applicable) after the final injection of the first treatment period (after randomization in the non-treatment group) ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Percent change from baseline in strabismus angle in the primary position at Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle
Duration of effect [ Time Frame: Up to Week 48 after the final injection of the first treatment period ] [ Designated as safety issue: No ]
Mean value of distant-view strabismus angle and near-view strabismus angle will be evaluated as strabismus angle. Duration of effect is definied as the number of days after the final injection of the first treatment period (after randomization in the non-treatment group) until the date of first recording a value smaller than 50% in percent correction compared to maximum change in strabismus angle in the primary position
Severity of duction limitation at Weeks 1, 2 and 4 of the first treatment period [ Time Frame: Weeks 1, 2 and 4 of the first treatment period ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients
Severity of duction limitation at Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the first treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 (before reinjection of the second treatment period if applicable) after the final injection of the first treatment period (after randomization in the non-treatment group) ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients
Severity of duction limitation at Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients
Change from baseline in severity of duction limitation at Weeks 1, 2 and 4 of the first treatment period [ Time Frame: Weeks 1, 2 and 4 of the first treatment period ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients
Change from baseline in severity of duction limitation at Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the first treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 (before reinjection of the second treatment period if applicable) after the final injection of the first treatment period (after randomization in the non-treatment group) ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients
Change from baseline in severity of duction limitation at Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20 and 24 of the second treatment period ] [ Designated as safety issue: No ]
Severity of duction limitation will be assessed by a 6-point scale (score range: from 0=No duction limitation to -5=Cannot rotate eye to midline) for paralytic strabismus patients

Estimated Enrollment:	66
Study Start Date:	May 2012
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: Non-treatment (10-20 PD) Receive no treatment on Week 0
Active Comparator: GSK1358820 1.25 U (10-20 PD) Receive 1.25 U of GSK1358820 on Week 0	Drug: GSK1358820 IM injection of Botulinum Toxin Type A Other Name: Botulinum Toxin Type A
Active Comparator: GSK1358820 2.5 U (10-20 PD) Receive 2.5 U of GSK1358820 on Week 0	Drug: GSK1358820 IM injection of Botulinum Toxin Type A Other Name: Botulinum Toxin Type A
No Intervention: Non-treatment (20-50 PD) Receive no treatment on Week 0
Active Comparator: GSK1358820 2.5 U (20-50 PD) Receive 2.5 U of GSK1358820 on Week 0	Drug: GSK1358820 IM injection of Botulinum Toxin Type A Other Name: Botulinum Toxin Type A
Active Comparator: GSK1358820 5.0 U (20-50 PD) Receive 5.0 U of GSK1358820 on Week 0	Drug: GSK1358820 IM injection of Botulinum Toxin Type A Other Name: Botulinum Toxin Type A

Detailed Description:

Primary objective is to evaluate the efficacy of single-dose treatment with GSK1358820 compared with non-treatment in patients with strabismus based on angles of strabismus in the primary position. Secondary objective is to evaluate the efficacy and safety of repeated-dose treatment with GSK1358820 in patients with strabismus.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Paralytic or concomitant strabismus. Subjects with paralytic strabismus will be eligible for inclusion only if paralysis has persisted for at least 3 months and strabismus has been developed at one eye
Horizontal deviations (esotropia or exotropia)
Strabismus with the (absolute) strabismus angles at both distance and near of primary position >-10 PD and <50 PD
Age>-12 years at the time of giving informed consent
The subject has to be capable of giving written informed consent of their own will. For subjects aged less than 20 years, the subject and his/her legally acceptable representative (person in parental authority or guardian) have to give written informed consent
Either sex. Males have to agree to practice contraception during the study period. Females of child-bearing potential will be eligible for inclusion in this study. However, they have to have negative pregnancy test both at the screening visit and just before initial injection and agree to practice reliable methods of contraception
QTc <450 msec; for patients with Bundle Branch Block, QTc <480 msec based on average QTc value of triplicate ECGs <At the start of treatment period >
Strabismus with the (absolute) strabismus angles at both distance and near of primary position >-10 PD and <50 PD
ALT at the screening visit <2 x ULN and alkaline phosphatase and bilirubin <-1.5 x ULN

Exclusion Criteria:

Past surgical treatment of strabismus
Strabismus due to abnormal innervations
Strabismus with thyroid-associated ophthalmopathy
Strabismus with strong motor limitation of extraocular muscles
Mechanical limitations of ocular movement due to periorbital disease or due to past surgical treatment other than strabismus
Blepharoptosis
Conjunctival pathology
Systemic neuromuscular junction dysfunction
Systemic neuromuscular disease
Past treatment with botulinum toxin
Planned injections of botulinum toxin for other indication(s) or for cosmetic purpose during the study period
Known hypersensitivity to any of the drugs to be used in the study or history of allergy
Treatment with antibiotics with neuromuscular junction inhibitory action such as aminoglycosides, polypeptides, tetracyclines and lincomycins, except those contained in topical antibacterial formulations
Treatment with muscle relaxants or drugs with muscle relaxant action
Chronic respiratory disorder
Severe muscle weakness or atrophy
Angle-closure glaucoma or its predisposing factors
Severe cardiac, hepatic or renal impairment. The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences" (MHLW PAB/SD Notification No. 80, dated 29 June 1992).
Surgical operation or hospitalization to be needed during the study period
Female subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study period
Participation in another clinical study within 6 months prior to enrollment in this study or planned participation in another clinical study after enrollment in this study
Psychiatric disorder or impairment of intellectual function that may affect the subject's ability to give informed consent or to comply with the trial procedures
History of alcohol dependence or drug abuse
Subjects whom the investigator (or sub-investigator) considers ineligible for the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584843

Contacts

Contact: US GSK Clinical Trials Call Center

877-379-3718

GSKClinicalSupportHD@gsk.com

Locations

Japan
GSK Investigational Site	Not yet recruiting
Aichi, Japan, 494-0001
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Fukuoka, Japan, 812-0011
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Hyogo, Japan, 663-8501
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Kagoshima, Japan, 890-0046
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Kanagawa, Japan, 252-0375
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Miyazaki, Japan, 885-0051
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Miyazaki, Japan, 880-0035
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Osaka, Japan, 535-0021
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Osaka, Japan, 569-8686
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Shizuoka, Japan, 431-3192
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Tokyo, Japan, 101-0062
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Not yet recruiting
Tokyo, Japan, 134-0088
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com
GSK Investigational Site	Recruiting
Yamaguchi, Japan, 750-0061
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 8990 4466 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01584843 History of Changes
Other Study ID Numbers:	116246
Study First Received:	April 23, 2012
Last Updated:	March 14, 2013
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:

Botulinum Toxin Type A
Neuromuscular Agents
Strabismus

Additional relevant MeSH terms:

Ocular Motility Disorders
Strabismus
Cranial Nerve Diseases
Nervous System Diseases
Eye Diseases
Botulinum Toxins, Type A
Neuromuscular Agents

Botulinum Toxins
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013