Clinical trial NCT01584843: Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Strabismus
Keywords: Neuromuscular Agents
Strabismus
Botulinum Toxin Type A
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 41
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

\<At the start of screening period\>

* 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:

\<At the start of screening period\>

* Secondary strabismus caused by prior surgical recession of the antagonist in 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

Primary outcomes:
measure: Change From Baseline in Strabismus Angle Prism Dioptre (PD) in the Primary Position at Week 4 of the FTP in Observed Cases (OC)
timeFrame: Baseline and Week 4 of the FTP
Secondary outcomes:
measure: Change From Baseline in the Strabismus Angle Prism Dioptre (PD) in the Primary Position at Week 1 After the Initial Injection of the FTP in Observed Cases (OC)
timeFrame: Baseline and Week 1 of the FTP
measure: Change From Baseline in the Strabismus Angle PD in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 After the Final Injection of the FTP
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the FTP
measure: Change From Baseline in the Strabismus Angle PD in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, and 24 of the Second Treatment Period (STP)
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
measure: Absolute Strabismus Angle in the Primary Position at Weeks 1 and 4 of the FTP
timeFrame: Weeks 1 and 4 of the FTP
measure: Absolute Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 After the Final Injection of the FTP
timeFrame: Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the FTP
measure: Absolute Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
timeFrame: Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
measure: Percent Change From Baseline in the Strabismus Angle in the Primary Position at Week 1 and Week 4 in Observed Cases (OC) of the FTP
timeFrame: Baseline and Weeks 1 and 4 of the FTP
measure: Percent Change From Baseline in the Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 After the Final Injection of the FTP
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 of the FTP
measure: Percent Change From Baseline in the Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
measure: Duration of Effect
timeFrame: Up to Week 48 after the final injection of the FTP (up to Study Week 52)
measure: Severity of Duction Limitation at Weeks 1 and 4 of the FTP
timeFrame: Week 1 and Week 4 of the FTP
measure: Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 After the Final Injection of the FTP
timeFrame: Weeks 1, 4, 8, 12, 16, 20, and 24 after the final injection of the FTP (up to a maximum of 52 weeks of the FTP)
measure: Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
timeFrame: Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
measure: Change From Baseline in the Severity of Duction Limitation at Weeks 1 and 4 of the FTP
timeFrame: Baseline and Weeks 1 and 4 of the FTP
measure: Change From Baseline in the Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 After the Final Injection of the FTP
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the FTP (up to a maximum of 52 weeks of the FTP)
measure: Change From Baseline in the Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
timeFrame: Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyazaki
country: Japan
facility: GSK Investigational Site
city: Miyazaki
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamaguchi
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: