search
Back to results

Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus

Primary Purpose

Strabismus

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
GSK1358820
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Strabismus focused on measuring Neuromuscular Agents, Strabismus, Botulinum Toxin Type A

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

No Intervention

Active Comparator

Active Comparator

No Intervention

Active Comparator

Active Comparator

Arm Label

Non-treatment (10-20 PD)

GSK1358820 1.25 U (10-20 PD)

GSK1358820 2.5 U (10-20 PD)

Non-treatment (20-50 PD)

GSK1358820 2.5 U (20-50 PD)

GSK1358820 5.0 U (20-50 PD)

Arm Description

Receive no treatment on Week 0

Receive 1.25 U of GSK1358820 on Week 0

Receive 2.5 U of GSK1358820 on Week 0

Receive no treatment on Week 0

Receive 2.5 U of GSK1358820 on Week 0

Receive 5.0 U of GSK1358820 on Week 0

Outcomes

Primary Outcome Measures

Change From Baseline in Strabismus Angle Prism Dioptre (PD) in the Primary Position at Week 4 of the FTP in Observed Cases (OC)
The strabismus angle in the primary position was measured using the alternative prism cover test (APCT). The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 meters [m]) and the near-view strabismus angle (measured at a distance of 33 centimeters [cm]). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the value at Week 4 minus the value at Baseline.

Secondary Outcome Measures

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)
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the value at Week 1minus the value at Baseline.
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
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for the observed cases for the change in the strabismus angle in the primary position from Baseline at Weeks 1, 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 FTP (after randomization in the non-treatment groups). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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)
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Absolute Strabismus Angle in the Primary Position at Weeks 1 and 4 of the FTP
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The absolute values of the strabismus angle in the primary position at Week 1 and Week 4 of the FTP were summarized for observed cases without imputation of missing values.
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
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The absolute values of the strabismus angle in the primary position were summarized for observed cases at Weeks 1, 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 FTP (after randomization in the non-treatment groups).
Absolute Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period.
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
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for observed cases for the percent change from Baseline in the strabismus angle in the primary position at Week 1and Week 4 after the initial injection in the FTP. Percent change from Baseline in the strabismus angle was calculated as: absolute angle ([strabismus angle at Baseline minus strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by 100.
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
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for observed cases for 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 (before reinjection of the second treatment period if applicable) after the final injection of the FTP (after randomization in non-treatment groups; up to a maximum of 52 weeks of the FTP). Percent change from Baseline in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by
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
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Percent change from Baseline in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by 100.
Duration of Effect
Duration of effect is defined as the number of days after the final injection of the FTP (after randomization in the non-treatment groups) until the date of the first recording of a value smaller than 50% in percent correction compared to the maximum change in the strabismus angle in the primary position. The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Percent correction compared to the maximum change in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after injection]/absolute angle [strabismus angle at Baseline minus the strabismus angle at maximum change]) multiplied by 100.
Severity of Duction Limitation at Weeks 1 and 4 of the FTP
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction is limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline.
Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 After the Final Injection of the FTP
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction is limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline.
Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. All participants with paralytic strabismus did not receive a second injection so there were no participants to analyse for this outcome measure.
Change From Baseline in the Severity of Duction Limitation at Weeks 1 and 4 of the FTP
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
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
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in the Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. All participants with paralytic strabismus did not receive a second injection so there were no participants to analyse for this outcome measure.

Full Information

First Posted
April 23, 2012
Last Updated
July 2, 2015
Sponsor
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT01584843
Brief Title
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

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Strabismus
Keywords
Neuromuscular Agents, Strabismus, Botulinum Toxin Type A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Non-treatment (10-20 PD)
Arm Type
No Intervention
Arm Description
Receive no treatment on Week 0
Arm Title
GSK1358820 1.25 U (10-20 PD)
Arm Type
Active Comparator
Arm Description
Receive 1.25 U of GSK1358820 on Week 0
Arm Title
GSK1358820 2.5 U (10-20 PD)
Arm Type
Active Comparator
Arm Description
Receive 2.5 U of GSK1358820 on Week 0
Arm Title
Non-treatment (20-50 PD)
Arm Type
No Intervention
Arm Description
Receive no treatment on Week 0
Arm Title
GSK1358820 2.5 U (20-50 PD)
Arm Type
Active Comparator
Arm Description
Receive 2.5 U of GSK1358820 on Week 0
Arm Title
GSK1358820 5.0 U (20-50 PD)
Arm Type
Active Comparator
Arm Description
Receive 5.0 U of GSK1358820 on Week 0
Intervention Type
Drug
Intervention Name(s)
GSK1358820
Other Intervention Name(s)
Botulinum Toxin Type A
Intervention Description
IM injection of Botulinum Toxin Type A
Primary Outcome Measure Information:
Title
Change From Baseline in Strabismus Angle Prism Dioptre (PD) in the Primary Position at Week 4 of the FTP in Observed Cases (OC)
Description
The strabismus angle in the primary position was measured using the alternative prism cover test (APCT). The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 meters [m]) and the near-view strabismus angle (measured at a distance of 33 centimeters [cm]). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the value at Week 4 minus the value at Baseline.
Time Frame
Baseline and Week 4 of the FTP
Secondary Outcome Measure Information:
Title
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)
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the value at Week 1minus the value at Baseline.
Time Frame
Baseline and Week 1 of the FTP
Title
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
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for the observed cases for the change in the strabismus angle in the primary position from Baseline at Weeks 1, 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 FTP (after randomization in the non-treatment groups). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the FTP
Title
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)
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
Title
Absolute Strabismus Angle in the Primary Position at Weeks 1 and 4 of the FTP
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The absolute values of the strabismus angle in the primary position at Week 1 and Week 4 of the FTP were summarized for observed cases without imputation of missing values.
Time Frame
Weeks 1 and 4 of the FTP
Title
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
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The absolute values of the strabismus angle in the primary position were summarized for observed cases at Weeks 1, 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 FTP (after randomization in the non-treatment groups).
Time Frame
Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 after the final injection of the FTP
Title
Absolute Strabismus Angle in the Primary Position at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period.
Time Frame
Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
Title
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
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for observed cases for the percent change from Baseline in the strabismus angle in the primary position at Week 1and Week 4 after the initial injection in the FTP. Percent change from Baseline in the strabismus angle was calculated as: absolute angle ([strabismus angle at Baseline minus strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by 100.
Time Frame
Baseline and Weeks 1 and 4 of the FTP
Title
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
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. The values were summarized for observed cases for 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 (before reinjection of the second treatment period if applicable) after the final injection of the FTP (after randomization in non-treatment groups; up to a maximum of 52 weeks of the FTP). Percent change from Baseline in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 of the FTP
Title
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
Description
The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Every participant's evaluation was performed in the same affected eye (left or right) throughout the study period. Percent change from Baseline in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after the final injection] divided by the absolute strabismus angle at Baseline) multiplied by 100.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
Title
Duration of Effect
Description
Duration of effect is defined as the number of days after the final injection of the FTP (after randomization in the non-treatment groups) until the date of the first recording of a value smaller than 50% in percent correction compared to the maximum change in the strabismus angle in the primary position. The strabismus angle in the primary position was measured using the APCT. The strabismus angle was evaluated as the mean value of the distant-view strabismus angle (measured at a distance of 5 m) and the near-view strabismus angle (measured at a distance of 33 cm). Percent correction compared to the maximum change in the strabismus angle was calculated as: (absolute angle [strabismus angle at Baseline minus the strabismus angle after injection]/absolute angle [strabismus angle at Baseline minus the strabismus angle at maximum change]) multiplied by 100.
Time Frame
Up to Week 48 after the final injection of the FTP (up to Study Week 52)
Title
Severity of Duction Limitation at Weeks 1 and 4 of the FTP
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction is limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline.
Time Frame
Week 1 and Week 4 of the FTP
Title
Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 After the Final Injection of the FTP
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction is limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline.
Time Frame
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)
Title
Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. All participants with paralytic strabismus did not receive a second injection so there were no participants to analyse for this outcome measure.
Time Frame
Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)
Title
Change From Baseline in the Severity of Duction Limitation at Weeks 1 and 4 of the FTP
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
Baseline and Weeks 1 and 4 of the FTP
Title
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
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame
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)
Title
Change From Baseline in the Severity of Duction Limitation at Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP
Description
The severity of duction limitation was calculated for participants with paralytic strabismus. For each evaluable participant, assessment was done by taking a frontal photo of the condition of the affected eye to determine the maximum movement toward the direction to which duction was limited while the non-affected eye was masked with eye-patch. The evaluation was performed in the same eye (left or right) throughout the study period. Based on the photos, the severity of the duction limitation was assessed on a 6-point scale, with scores ranging from 0=no duction limitation to -5=cannot rotate eye to midline. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. All participants with paralytic strabismus did not receive a second injection so there were no participants to analyse for this outcome measure.
Time Frame
Baseline and Weeks 1, 4, 8, 12, 16, 20, and 24 of the STP (up to Study Week 52)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
494-0001
Country
Japan
Facility Name
GSK Investigational Site
City
Fukuoka
ZIP/Postal Code
812-0011
Country
Japan
Facility Name
GSK Investigational Site
City
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
GSK Investigational Site
City
Kagoshima
ZIP/Postal Code
890-0046
Country
Japan
Facility Name
GSK Investigational Site
City
Kanagawa
ZIP/Postal Code
252-0375
Country
Japan
Facility Name
GSK Investigational Site
City
Miyazaki
ZIP/Postal Code
880-0035
Country
Japan
Facility Name
GSK Investigational Site
City
Miyazaki
ZIP/Postal Code
885-0051
Country
Japan
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
535-0021
Country
Japan
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
569-8686
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
101-0062
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
134-0088
Country
Japan
Facility Name
GSK Investigational Site
City
Yamaguchi
ZIP/Postal Code
750-0061
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus

We'll reach out to this number within 24 hrs