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Clinical Study to Investigate Safety and Efficacy of GSK933776 in Adult Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01342926
Collaborator
(none)
191
Enrollment
41
Locations
4
Arms
58
Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of GSK933776 in the treatment of geographic atrophy secondary to age-related macular degeneration.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a Phase 2a proof of concept study designed to evaluate the safety and efficacy of GSK933776 for the treatment of geographic atrophy secondary to age-related macular degeneration. This is a placebo-controlled parallel-group study that is double masked.

Study Design

Study Type:
Interventional
Actual Enrollment :
191 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multi-centre, Randomised, Double-masked, Placebo-controlled, Parallel-group Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of GSK933776 in Adult Patients With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)
Study Start Date :
Jun 1, 2011
Actual Primary Completion Date :
Apr 1, 2016
Actual Study Completion Date :
Apr 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: GSK933776 3 mg/kg

3 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776
GSK933776
Experimental: GSK933776 6 mg/kg

6 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776
GSK933776
Placebo Comparator: Placebo

Placebo via intravenous infusion

Drug: Placebo
Placebo
Experimental: GSK933776 15 mg/kg

15 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776
GSK933776

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye [Baseline (BL), 6 months, 12 months and 18 months]

    Atrophic age-related macular degeneration (AMD) also called GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by color FP at the indicated time points: screening, 6 months, 12 months and 18 months. Change from BL: (screening, month 6, 12 or 18 value minus BL value. Note screening occurs prior to BL). Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Efficacy Population: all participants in the Intent-to-Treat (ITT) Population who met the protocol defined inclusion criterion for area of GA assessed by color FP in the study eye in at least one visit from screening visit through BL visit, inclusive and had data of area of GA assessed by fundus autofluorescence images in the study eye for at least 75% of the visits (>=14 visits) from post-BL treatment month 2 visit to treatment month 19 visit.

  2. Number of Participants With Ocular or Non-ocular Adverse Events (AEs) During the Treatment Period [Up to 21 months]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It includes:1. Any abnormal laboratory test results or other safety assessments including those that worsen from Baseline, and felt to be clinically significant in the medical and scientific judgment of the Investigator 2.Exacerbation (increase in frequency/intensity) of a chronic or intermittent pre-existing condition 3. New conditions detected or diagnosed after screening visit 4. Signs, symptoms, or the clinical sequelae of a suspected interaction/suspected overdose of investigational product or a concomitant medication. AEs were presented as non-ocular and ocular AEs.

  3. Number of Participants With Ocular or Non-ocular Serious Adverse Events (SAEs) During the Treatment Period [Up to 21 months]

  4. Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Up to 21 months]

    Vital signs included SBP and DBP of Potential Clinical Importance (PCI) at the indicated time points: Baseline, month 0, month 1, month 2, month 3, month 4, month 5, month 6, month 7, month 8, month 9, month 10, month 11, month 12, month 13, month 14, month 15, month 16, month 17, month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. SBP was defined as: low: <85 millimeter of mercury (mmHg) and high: >160 mmHg and DBP was defined as: low:<45 mmHg and high: >100 mmHg. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.

  5. Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Heart Rate (HR) [Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit]

    Vital signs included HR of CCR at the indicated time points: Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. HR was defined as: low:< 40 beats per minute (bpm) and high: >100 bpm. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.

  6. Number of Participants With 12-lead Electrocardiogram (ECG) of Potential Clinical Importance (PCI) [Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit]

    12-lead ECG was obtained after 10 minutes rest in a supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Abnormal-clinically significant (CS) ECG measurements are presented at indicated time points: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

  7. Number of Participants With Abnormal Laboratory Parameter Values of Potential Clinical Importance (PCI) [At any point from Baseline through follow-up visit.]

    The following laboratory parameters were assessed: Hematology: Platelet Count, Red Blood Cell Count, White Blood Cell (WBC) Count, Reticulocyte Count, Hemoglobin, Hematocrit, Prothrombin time-International Normalized Ratio, Activated partial thromboplastin time, Mean corpuscular volume, Mean corpuscular haemoglobin, Mean corpuscular hemoglobin concentration, Neutrophils (ANC), Lymphocytes, Monocytes, Eosinophils, and Basophils. Clinical chemistry: Blood urea nitrogen, Potassium, Aspartate aminotransferase, Total and direct bilirubin Creatinine, Chloride, Alanine aminotransferase, Uric Acid, Glucose (fasting), Total Carbon dioxide , Gamma glutamyltransferase, Albumin, Sodium, Calcium, Alkaline phosphatase, Total Protein, and HbA1c. Urine: Specific gravity, pH, glucose, protein, blood and ketones and Microscopic examination. Only those with PCIs are displayed.

  8. Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) [Month 2, Month 3, Month 4, Month 6, Month 12, Month 18 and at early withdrawal]

    Magnetic Resonance Imaging (MRI) was used as a safety assessment to monitor for amyloid related imaging abnormalities (ARIA) events in the brain. MRIs were performed at Baseline and before dose 2, before dose 3, before dose 4, before dose 6, before dose 12, before dose 18 and at follow-up. ARIA-edema/effusions (ARIA-E) and ARIA hemosiderin deposition (ARIA-H) events at any visit are reported.

Secondary Outcome Measures

  1. Change From Baseline in Area of GA Assessed by Fundus Autofluorescence Images (hypoAF) Corresponding to GA in Study Eye [Baseline, 6 months, 12 months and 18 months]

    Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence images in the study eye at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (months 6, 12,18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

  2. Change From Baseline in Area of Total hypoAF in Study Eye [Baseline, 6 months, 12 months and 18 months]

    Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (Month 6, 12, 18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

  3. Number of Participants Losing Letters in Early Treatment Diabetic Retinopathy Study (ETDRS)-Best Corrected Visual Acuity (BCVA) Score at Month 12 and Month 18 for Each Eye [Month 12 and Month 18]

    Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed at the indiated time points at: Month 12 and Month 18 with categorical changes in the number of participants losing >30, >=15, >=10, >=5 and <5 letters.

  4. Mean Change in ETDRS-BCVA Score From Baseline at Every Month up to Month 18 [Baseline and every month up to Month 18]

    Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed as change from baseline in the mean best-corrected ETDRS visual acuity score at 18 months. Change from Baseline is defined as post-dose visit value minus Baseline value. Note that screening occurs before baseline. Values were truncated to one decimal place and negative sign retained where value is negative and the truncated value is zero. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

  5. Area Under the Plasma Concentration-time Curve From Time 0 to the End of Dosing Interval at Steady-state (AUC0-28d) of GSK933776 in Geographic Atrophy Participants [Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476]

    Area under the plasma concentration-time curve from time 0 to the end of dosing interval at steady-state; derived from dose and clearance parameters was evaluated. Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.

  6. Maximum Observed Plasma Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK933776 in Geographic Atrophy Participants [Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476]

    Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

  7. Clearance (CL) of GSK933776 in Geographic Atrophy Participants [Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476]

    Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.

  8. Estimation of Terminal Phase Half-life (T1/2) of GSK933776 in Geographic Atrophy Participants [Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476]

    Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.

  9. Volume of Distribution at Steady-state (Vdss) of GSK933776 in Geographic Atrophy Participants Estimated From Population PK Modeling [Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476]

    Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.

  10. The Pharmacodynamic Effects of GSK933776 Total (Bound and Unbound) Plasma Total Amyloid Beta (Abeta42), and Amyloid Beta Fragments (Abeta18-35), if Possible, Unbound Plasma Aβ Fragments (Abeta1-22) [Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18]

    Blood samples were collected at the indicated time points on Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Eligibility Criteria

Criteria

Ages Eligible for Study:
55 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Adult patients ≥55 years of age inclusive

  • Evidence of AMD confirmed by the presence of at least 1 druse ≥125 μm diameter

  • Well-demarcated GA due to AMD of total area 1.9-17 mm2 measured in the study eye

  • Best-corrected visual acuity score of ≥ 35 letters (approximately 20/200 Snellen VA equivalent or better) in the study eye

Exclusion Criteria:

  • Additional eye disease in the study eye that could compromise assessment of best-corrected visual acuity or imaging of the posterior pole

  • History of CNV secondary to AMD in the study eye

  • Any previous treatment for AMD in the study eye, approved or investigational, with the exception of dietary supplements

  • Risk of cerebrovascular disease, cerebral hemorrhage or stroke

  • History of systemic autoimmune disease

  • Use of platelet anti-aggregants or anti-coagulants (aspirin up to 325 mg/day is allowable, or in subjects allergic or intolerable to aspirin, clopidogrel up to 75 mg/day is allowable)

  • Use of chronic corticosteroids

  • Uncontrolled hypertension in spite of antihypertensive medications

  • Renal or hepatic insufficiency or clinically significant anemia

  • More than moderate MRI white matter changes

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Phoenix Arizona United States 85014
2 GSK Investigational Site Phoenix Arizona United States 85020
3 GSK Investigational Site Arcadia California United States 91007
4 GSK Investigational Site Irvine California United States 92697
5 GSK Investigational Site La Jolla California United States 92037
6 GSK Investigational Site Los Angeles California United States 90033-4500
7 GSK Investigational Site Palm Desert California United States 92260
8 GSK Investigational Site San Francisco California United States 94143
9 GSK Investigational Site Torrance California United States 90503
10 GSK Investigational Site Golden Colorado United States 80401
11 GSK Investigational Site Miami Florida United States 33136
12 GSK Investigational Site Stuart Florida United States 34994
13 GSK Investigational Site Tampa Florida United States 33612
14 GSK Investigational Site Augusta Georgia United States 30909
15 GSK Investigational Site Indianapolis Indiana United States 46290
16 GSK Investigational Site New Albany Indiana United States 47150
17 GSK Investigational Site Leawood Kansas United States 66211
18 GSK Investigational Site Prairie Village Kansas United States 66208
19 GSK Investigational Site Louisville Kentucky United States 40215
20 GSK Investigational Site Paducah Kentucky United States 42001
21 GSK Investigational Site Baltimore Maryland United States 21204
22 GSK Investigational Site Baltimore Maryland United States 21287
23 GSK Investigational Site Boston Massachusetts United States 02111
24 GSK Investigational Site North Dartmouth Massachusetts United States 02747
25 GSK Investigational Site Detroit Michigan United States 48202
26 GSK Investigational Site Northfield New Jersey United States 08225
27 GSK Investigational Site Toms River New Jersey United States 08755
28 GSK Investigational Site New York New York United States 10003
29 GSK Investigational Site Philadelphia Pennsylvania United States 19104
30 GSK Investigational Site Philadelphia Pennsylvania United States 19107
31 GSK Investigational Site West Mifflin Pennsylvania United States 15122
32 GSK Investigational Site Ladson South Carolina United States 29406
33 GSK Investigational Site Nashville Tennessee United States 37203
34 GSK Investigational Site Abilene Texas United States 79606
35 GSK Investigational Site Austin Texas United States 78705
36 GSK Investigational Site Galveston Texas United States 77550
37 GSK Investigational Site Houston Texas United States 77030
38 GSK Investigational Site Salt Lake City Utah United States 84132
39 GSK Investigational Site Charlottesville Virginia United States 22903
40 GSK Investigational Site Silverdale Washington United States 98383
41 GSK Investigational Site Mississauga Ontario Canada L4W 1W9

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01342926
Other Study ID Numbers:
  • 114341
First Posted:
Apr 27, 2011
Last Update Posted:
May 5, 2017
Last Verified:
Mar 1, 2017
Keywords provided by GlaxoSmithKline
age-related macular degeneration
geographic atrophy
dry AMD
Additional relevant MeSH terms:
Macular Degeneration
Geographic Atrophy
Atrophy

Study Results

Participant Flow

Recruitment Details This study was a parallel-group randomized study consisted of a screening visit, where 240 participants entered the observation period (minimum of 4 months), a Baseline visit at the end of observation phase, where 191 were randomized, and was followed by the treatment period (18 months), and a follow-up visit (3 months) after last dose.
Pre-assignment Detail The total duration of participation was approximately 25 months following screening.
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Period Title: Overall Study
STARTED 46 46 48 51
COMPLETED 37 31 34 39
NOT COMPLETED 9 15 14 12

Baseline Characteristics

Arm/Group Title Placebo GSK933776 3 mg/kg GSK933776 6 mg/kg GSK933776 15 mg/kg Total
Arm/Group Description Placebo via intravenous infusion 3 mg/kg administration of GSK933776 via intravenous infusion 6 mg/kg administration of GSK933776 via intravenous infusion 15 mg/kg administration of GSK933776 via intravenous infusion Total of all reporting groups
Overall Participants 46 46 48 51 191
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
75.3
(9.55)
77.2
(9.09)
77.5
(8.57)
78.6
(7.22)
77.2
(8.63)
Sex: Female, Male (Count of Participants)
Female
27
58.7%
29
63%
26
54.2%
27
52.9%
109
57.1%
Male
19
41.3%
17
37%
22
45.8%
24
47.1%
82
42.9%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage
1
2.2%
0
0%
0
0%
0
0%
1
0.5%
White
45
97.8%
46
100%
48
100%
51
100%
190
99.5%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye
Description Atrophic age-related macular degeneration (AMD) also called GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by color FP at the indicated time points: screening, 6 months, 12 months and 18 months. Change from BL: (screening, month 6, 12 or 18 value minus BL value. Note screening occurs prior to BL). Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Efficacy Population: all participants in the Intent-to-Treat (ITT) Population who met the protocol defined inclusion criterion for area of GA assessed by color FP in the study eye in at least one visit from screening visit through BL visit, inclusive and had data of area of GA assessed by fundus autofluorescence images in the study eye for at least 75% of the visits (>=14 visits) from post-BL treatment month 2 visit to treatment month 19 visit.
Time Frame Baseline (BL), 6 months, 12 months and 18 months

Outcome Measure Data

Analysis Population Description
Efficacy Population. Participants who developed CNV in the study eye during the treatment period are excluded from Efficacy Population per protocol.
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 34 30 35 40
Screening, n=34, 30, 35, 40
-0.52
-0.94
-0.99
-0.96
6 months, n=34, 30, 35, 39
0.95
0.88
0.73
0.77
12 months, n=33, 29, 34, 40
1.60
1.81
1.83
1.89
18 months, n=34, 30, 32, 39
2.60
2.77
2.88
2.99
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 90%
-0.57 to 0.43
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.20
Confidence Interval (2-Sided) 90%
-0.31 to 0.71
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 90%
-0.33 to 0.68
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 90%
-0.71 to 0.26
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.23
Confidence Interval (2-Sided) 90%
-0.26 to 0.72
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.28
Confidence Interval (2-Sided) 90%
-0.21 to 0.77
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 90%
-0.66 to 0.29
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.28
Confidence Interval (2-Sided) 90%
-0.19 to 0.75
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.39
Confidence Interval (2-Sided) 90%
-0.08 to 0.86
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
2. Primary Outcome
Title Number of Participants With Ocular or Non-ocular Adverse Events (AEs) During the Treatment Period
Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It includes:1. Any abnormal laboratory test results or other safety assessments including those that worsen from Baseline, and felt to be clinically significant in the medical and scientific judgment of the Investigator 2.Exacerbation (increase in frequency/intensity) of a chronic or intermittent pre-existing condition 3. New conditions detected or diagnosed after screening visit 4. Signs, symptoms, or the clinical sequelae of a suspected interaction/suspected overdose of investigational product or a concomitant medication. AEs were presented as non-ocular and ocular AEs.
Time Frame Up to 21 months

Outcome Measure Data

Analysis Population Description
ITT Population: all participants that completed the observation period and Baseline visit, and were subsequently randomized to treatment and were administered at least one IV dose.
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
Non-ocular AEs
41
89.1%
42
91.3%
44
91.7%
47
92.2%
Ocular AEs
12
26.1%
17
37%
15
31.3%
20
39.2%
3. Primary Outcome
Title Number of Participants With Ocular or Non-ocular Serious Adverse Events (SAEs) During the Treatment Period
Description
Time Frame Up to 21 months

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
Non-ocular SAEs
8
17.4%
11
23.9%
9
18.8%
12
23.5%
Ocular SAEs
1
2.2%
0
0%
0
0%
0
0%
4. Primary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description Vital signs included SBP and DBP of Potential Clinical Importance (PCI) at the indicated time points: Baseline, month 0, month 1, month 2, month 3, month 4, month 5, month 6, month 7, month 8, month 9, month 10, month 11, month 12, month 13, month 14, month 15, month 16, month 17, month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. SBP was defined as: low: <85 millimeter of mercury (mmHg) and high: >160 mmHg and DBP was defined as: low:<45 mmHg and high: >100 mmHg. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Time Frame Up to 21 months

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
SBP Baseline General: > CCR, n=46, 46, 48, 51
1
2.2%
3
6.5%
2
4.2%
5
9.8%
SBP Baseline General 2:> CCR, n=46, 46, 48, 50
1
2.2%
2
4.3%
2
4.2%
4
7.8%
SBP Baseline General 3:> CCR, n=45, 46, 48, 50
1
2.2%
2
4.3%
2
4.2%
4
7.8%
SBP Month 0, Pre-dose:> CCR, n=46, 46, 48, 51
2
4.3%
1
2.2%
1
2.1%
1
2%
SBP Month 0, 0 H:> CCR, n=46, 46, 48, 51
1
2.2%
1
2.2%
2
4.2%
3
5.9%
SBP Month 1, Pre-dose:> CCR, n=44, 44, 44, 51
2
4.3%
5
10.9%
1
2.1%
2
3.9%
SBP Month 1, 0 H:> CCR, n=43, 44, 44, 51
3
6.5%
2
4.3%
1
2.1%
2
3.9%
SBP Month 2, Pre-dose:> CCR, n=44, 43, 42, 49
1
2.2%
2
4.3%
3
6.3%
2
3.9%
SBP Month 2, 0 H:> CCR, n=44, 41, 41, 49
1
2.2%
4
8.7%
1
2.1%
3
5.9%
SBP Month 3, Pre-dose:> CCR, n=44, 37, 42, 46
5
10.9%
2
4.3%
1
2.1%
4
7.8%
SBP Month 3, 0 H:> CCR, n=42, 35, 40, 46
2
4.3%
3
6.5%
0
0%
3
5.9%
SBP Month 4, Pre-dose:> CCR, n=43, 36, 42, 46
1
2.2%
4
8.7%
0
0%
3
5.9%
SBP Month 4, 0 H:> CCR, n=43, 34, 42, 46
1
2.2%
2
4.3%
1
2.1%
3
5.9%
SBP Month 5, Pre-dose:> CCR, n=43, 36, 40, 45
0
0%
2
4.3%
2
4.2%
2
3.9%
SBP Month 5, 0 H:> CCR, n=42, 36, 39, 45
2
4.3%
4
8.7%
0
0%
4
7.8%
SBP Month 6, Pre-dose:> CCR, n=43, 36, 40, 45
0
0%
3
6.5%
1
2.1%
3
5.9%
SBP Month 6, 0 H:> CCR, n=42, 36, 40, 45
2
4.3%
1
2.2%
3
6.3%
3
5.9%
SBP Month 7, Pre-dose:> CCR, n=43, 35, 40, 44
1
2.2%
2
4.3%
2
4.2%
0
0%
SBP Month 7, 0 H:> CCR, n=43, 33, 40, 44
2
4.3%
0
0%
0
0%
0
0%
SBP Month 8, Pre-dose:> CCR, n=42, 33, 40, 44
2
4.3%
2
4.3%
1
2.1%
1
2%
SBP Month 8, 0 H:> CCR, n=41, 33, 40, 44
1
2.2%
3
6.5%
0
0%
1
2%
SBP Month 9, Pre-dose:> CCR, n=41, 33, 40, 44
1
2.2%
1
2.2%
0
0%
2
3.9%
SBP Month 9, Pre-dose:< CCR, n=41, 33, 40, 44
1
2.2%
0
0%
0
0%
0
0%
SBP Month 9, 0 H:> CCR, n=41, 33, 39, 44
0
0%
1
2.2%
0
0%
1
2%
SBP Month 10, Pre-dose:> CCR, n=41, 32, 40, 44
0
0%
0
0%
1
2.1%
0
0%
SBP Month 10, 0 H:> CCR, n=40, 32, 40, 44
1
2.2%
0
0%
0
0%
2
3.9%
SBP Month 11, Pre-dose:> CCR, n=41, 33, 39, 42
2
4.3%
2
4.3%
3
6.3%
2
3.9%
SBP Month 11, 0 H:> CCR, n=40, 31, 35, 41
1
2.2%
0
0%
1
2.1%
1
2%
SBP Month 11, 0 H:< CCR, n=40, 31, 35, 41
1
2.2%
0
0%
0
0%
0
0%
SBP Month 12, Pre-dose:> CCR, n=39, 30, 38, 41
2
4.3%
1
2.2%
1
2.1%
1
2%
SBP Month 12, 0 H:> CCR, n=39, 30, 38, 41
2
4.3%
1
2.2%
1
2.1%
2
3.9%
SBP Month 13, Pre-dose:> CCR, n=38, 31, 39, 39
0
0%
1
2.2%
1
2.1%
2
3.9%
SBP Month 13, 0 H:> CCR, n=38, 31, 39, 38
1
2.2%
0
0%
0
0%
1
2%
SBP Month 14, Pre-dose:> CCR, n=38, 31, 36, 39
0
0%
0
0%
1
2.1%
2
3.9%
SBP Month 14, 0 H:> CCR, n=38, 31, 36, 39
0
0%
0
0%
0
0%
1
2%
SBP Month 15, Pre-dose:> CCR, n=37, 31, 35, 39
0
0%
0
0%
1
2.1%
3
5.9%
SBP Month 15, 0 H:> CCR, n=37, 31, 35, 39
1
2.2%
0
0%
0
0%
0
0%
SBP Month 16, Pre-dose:> CCR, n=37, 31, 35, 39
1
2.2%
1
2.2%
0
0%
1
2%
SBP Month 16, 0 H:> CCR, n=37, 31, 35, 39
2
4.3%
2
4.3%
0
0%
0
0%
SBP Month 17, Pre-dose:> CCR, n=38, 32, 36, 40
2
4.3%
2
4.3%
1
2.1%
0
0%
SBP Month 17, 0 H:> CCR, n=37, 30, 34, 48
1
2.2%
2
4.3%
0
0%
1
2%
SBP Month 17, 0 H:< CCR, n=37, 30, 34, 48
0
0%
1
2.2%
0
0%
0
0%
SBP Month 18, General:> CCR, n=36, 31, 33, 39
1
2.2%
2
4.3%
1
2.1%
2
3.9%
SBP Early withdrawal, :> CCR, n=8, 8, 7, 4
0
0%
1
2.2%
1
2.1%
1
2%
SBP Follow-up:> CCR, n=39, 36, 37, 43
1
2.2%
0
0%
0
0%
1
2%
DBP Month 4, 0 H:< CCR, n=43, 34, 42, 46
1
2.2%
0
0%
0
0%
0
0%
DBP Month 8, 0 H:> CCR, n=41, 33, 40, 44
1
2.2%
0
0%
0
0%
0
0%
DBP Month 9, Pre-dose:> CCR, n=41, 33, 40, 44
0
0%
0
0%
0
0%
1
2%
DBP Month 11, Pre-dose:> CCR, n=41, 33, 39, 42
0
0%
0
0%
1
2.1%
0
0%
DBP Month 13, Pre-dose:< CCR, n=38, 31, 39, 39
0
0%
0
0%
1
2.1%
0
0%
5. Primary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Heart Rate (HR)
Description Vital signs included HR of CCR at the indicated time points: Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit in sitting position. 'General' is an assessment time not relative to dosing. HR was defined as: low:< 40 beats per minute (bpm) and high: >100 bpm. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Time Frame Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
HR Month 3, Pre-dose:> CCR, n=44, 37, 42, 46
1
2.2%
0
0%
0
0%
0
0%
HR Month 13, Pre-dose:> CCR, n=38, 31, 39, 39
0
0%
0
0%
1
2.1%
0
0%
6. Primary Outcome
Title Number of Participants With 12-lead Electrocardiogram (ECG) of Potential Clinical Importance (PCI)
Description 12-lead ECG was obtained after 10 minutes rest in a supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Abnormal-clinically significant (CS) ECG measurements are presented at indicated time points: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
ECG:CS Baseline, n=46, 46, 48, 51
1
2.2%
0
0%
1
2.1%
0
0%
ECG:CS Month 6, n=41, 33, 37, 44
0
0%
0
0%
1
2.1%
3
5.9%
ECG:CS Month 12, n=41, 32, 40, 40
0
0%
1
2.2%
1
2.1%
0
0%
ECG:CS Month 18, n=38, 30, 36, 35
0
0%
0
0%
2
4.2%
1
2%
ECG:CS early withdrawal, n=7, 8, 7, 3
0
0%
1
2.2%
2
4.2%
0
0%
ECG:CS follow-up, n=39, 37, 37, 38
0
0%
0
0%
1
2.1%
1
2%
7. Primary Outcome
Title Number of Participants With Abnormal Laboratory Parameter Values of Potential Clinical Importance (PCI)
Description The following laboratory parameters were assessed: Hematology: Platelet Count, Red Blood Cell Count, White Blood Cell (WBC) Count, Reticulocyte Count, Hemoglobin, Hematocrit, Prothrombin time-International Normalized Ratio, Activated partial thromboplastin time, Mean corpuscular volume, Mean corpuscular haemoglobin, Mean corpuscular hemoglobin concentration, Neutrophils (ANC), Lymphocytes, Monocytes, Eosinophils, and Basophils. Clinical chemistry: Blood urea nitrogen, Potassium, Aspartate aminotransferase, Total and direct bilirubin Creatinine, Chloride, Alanine aminotransferase, Uric Acid, Glucose (fasting), Total Carbon dioxide , Gamma glutamyltransferase, Albumin, Sodium, Calcium, Alkaline phosphatase, Total Protein, and HbA1c. Urine: Specific gravity, pH, glucose, protein, blood and ketones and Microscopic examination. Only those with PCIs are displayed.
Time Frame At any point from Baseline through follow-up visit.

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
Alanine Amino Transferase (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Alanine Amino Transferase (Above PCI high)
0
0%
1
2.2%
0
0%
0
0%
Aspartate Amino Transferase (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Aspartate Amino Transferase (Above PCI high)
1
2.2%
0
0%
0
0%
0
0%
Calcium (less than PCI low)
0
0%
0
0%
0
0%
1
2%
Calcium (Above PCI high)
1
2.2%
0
0%
1
2.1%
1
2%
CO2 content/Bicarbonate (less than PCI low)
10
21.7%
4
8.7%
9
18.8%
6
11.8%
CO2 content/B icarbonate (AbovePCI high)
0
0%
1
2.2%
0
0%
0
0%
Creatinine (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Creatinine (Above PCI high)
1
2.2%
0
0%
0
0%
0
0%
Glucose (less than PCI low)
0
0%
0
0%
0
0%
1
2%
Glucose (Above PCI high)
11
23.9%
17
37%
9
18.8%
10
19.6%
Potassium (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Potassium (Above PCI high)
1
2.2%
0
0%
0
0%
0
0%
Sodium (Less than PCI low)
2
4.3%
2
4.3%
0
0%
1
2%
Sodium (Above the PCI high)
0
0%
0
0%
0
0%
0
0%
Hemoglobin (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Hemoglobin (Above the PCI high)
3
6.5%
0
0%
0
0%
0
0%
Hematocrit (less than PCI low)
0
0%
0
0%
0
0%
0
0%
Hematocrit (Above PCI high)
5
10.9%
2
4.3%
2
4.2%
3
5.9%
Lymphocytes (less than PCI low)
2
4.3%
2
4.3%
1
2.1%
1
2%
Lymphocytes (Above PCI high)
0
0%
0
0%
0
0%
0
0%
Total ANC (less than PCI low)
4
8.7%
2
4.3%
1
2.1%
5
9.8%
Total ANC (Above PCI high)
0
0%
0
0%
0
0%
0
0%
Platelet count (less than PCI low)
2
4.3%
1
2.2%
0
0%
1
2%
Platelet count (Above PCI high)
0
0%
0
0%
0
0%
0
0%
WBC count (less than PCI low)
1
2.2%
0
0%
1
2.1%
0
0%
WBC count (Above PCI high)
0
0%
1
2.2%
0
0%
1
2%
8. Primary Outcome
Title Number of Participants With Abnormal Magnetic Resonance Imaging (MRI)
Description Magnetic Resonance Imaging (MRI) was used as a safety assessment to monitor for amyloid related imaging abnormalities (ARIA) events in the brain. MRIs were performed at Baseline and before dose 2, before dose 3, before dose 4, before dose 6, before dose 12, before dose 18 and at follow-up. ARIA-edema/effusions (ARIA-E) and ARIA hemosiderin deposition (ARIA-H) events at any visit are reported.
Time Frame Month 2, Month 3, Month 4, Month 6, Month 12, Month 18 and at early withdrawal

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
ARIA E
0
0%
0
0%
1
2.1%
1
2%
ARIA H
2
4.3%
4
8.7%
6
12.5%
4
7.8%
9. Secondary Outcome
Title Change From Baseline in Area of GA Assessed by Fundus Autofluorescence Images (hypoAF) Corresponding to GA in Study Eye
Description Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence images in the study eye at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (months 6, 12,18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Baseline, 6 months, 12 months and 18 months

Outcome Measure Data

Analysis Population Description
Efficacy Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 34 30 35 40
Screening, n=33, 30, 34, 40
-0.70
-0.62
-0.74
-0.74
6 months, n=33, 30, 34, 39
0.81
0.94
0.72
0.94
12 months, n=32, 29, 33, 40
1.33
1.74
1.67
1.87
18 months, n=33, 30, 31, 39
2.24
2.65
2.41
3.15
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.14
Confidence Interval (2-Sided) 90%
-0.34 to 0.61
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.41
Confidence Interval (2-Sided) 90%
-0.07 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.42
Confidence Interval (2-Sided) 90%
-0.06 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.09
Confidence Interval (2-Sided) 90%
-0.55 to 0.37
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.33
Confidence Interval (2-Sided) 90%
-0.13 to 0.80
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 90%
-0.30 to 0.63
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 90%
-0.31 to 0.57
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.54
Confidence Interval (2-Sided) 90%
0.10 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.91
Confidence Interval (2-Sided) 90%
0.47 to 1.36
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
10. Secondary Outcome
Title Change From Baseline in Area of Total hypoAF in Study Eye
Description Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (Month 6, 12, 18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Baseline, 6 months, 12 months and 18 months

Outcome Measure Data

Analysis Population Description
Efficacy Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 34 30 35 40
Screening, n=33, 30, 34, 40
-0.65
-0.63
-0.71
-1.20
6 months, n=33, 30, 34, 39
0.91
1.01
0.83
0.84
12 months, n=32, 29, 33, 40
1.44
1.90
1.67
1.64
18 months, n=33, 30, 31, 39
2.35
2.67
2.46
2.85
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.10
Confidence Interval (2-Sided) 90%
-0.34 to 0.55
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.45
Confidence Interval (2-Sided) 90%
0.00 to 0.90
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (3 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.33
Confidence Interval (2-Sided) 90%
-0.12 to 0.77
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 90%
-0.51 to 0.35
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.23
Confidence Interval (2-Sided) 90%
-0.21 to 0.66
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (6 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval (2-Sided) 90%
-0.32 to 0.55
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.06
Confidence Interval (2-Sided) 90%
-0.48 to 0.35
Parameter Dispersion Type:
Value:
Estimation Comments 6 months visit
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.20
Confidence Interval (2-Sided) 90%
-0.22 to 0.62
Parameter Dispersion Type:
Value:
Estimation Comments 12 months visit
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK933776 (15 mg/kg)
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.50
Confidence Interval (2-Sided) 90%
0.08 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments 18 months visit
11. Secondary Outcome
Title Number of Participants Losing Letters in Early Treatment Diabetic Retinopathy Study (ETDRS)-Best Corrected Visual Acuity (BCVA) Score at Month 12 and Month 18 for Each Eye
Description Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed at the indiated time points at: Month 12 and Month 18 with categorical changes in the number of participants losing >30, >=15, >=10, >=5 and <5 letters.
Time Frame Month 12 and Month 18

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
M12:Study eye, Losing > 30 letters
1
2.2%
0
0%
1
2.1%
1
2%
M12:Study eye, Losing >= 15 letters
3
6.5%
0
0%
2
4.2%
6
11.8%
M12:Study eye, Losing >= 10 letters
4
8.7%
1
2.2%
3
6.3%
9
17.6%
M12:Study eye, Losing >= 5 letters
11
23.9%
7
15.2%
10
20.8%
14
27.5%
M12:Study eye, Losing <5
28
60.9%
23
50%
28
58.3%
27
52.9%
M12:fellow eye, Losing > 30 letters
1
2.2%
0
0%
0
0%
1
2%
M12:fellow eye, Losing >= 15 letters
5
10.9%
0
0%
0
0%
2
3.9%
M12:fellow eye, Losing >= 10 letters
7
15.2%
3
6.5%
0
0%
3
5.9%
M12:fellow eye, Losing >= 5 letters
8
17.4%
6
13%
6
12.5%
11
21.6%
M12:fellow eye, Losing <5
31
67.4%
24
52.2%
31
64.6%
30
58.8%
M18:Study eye, Losing > 30 letters
1
2.2%
1
2.2%
2
4.2%
1
2%
M18:Study eye, Losing >= 15 letters
3
6.5%
1
2.2%
6
12.5%
5
9.8%
M18:Study eye, Losing >= 10 letters
10
21.7%
4
8.7%
9
18.8%
10
19.6%
M18:Study eye, Losing >= 5 letters
15
32.6%
10
21.7%
11
22.9%
12
23.5%
M18:Study eye, Losing <5
22
47.8%
21
45.7%
22
45.8%
27
52.9%
M18:fellow eye, Losing > 30 letters
2
4.3%
0
0%
0
0%
0
0%
M18:fellow eye, Losing >= 15 letters
4
8.7%
2
4.3%
1
2.1%
2
3.9%
M18:fellow eye, Losing >= 10 letters
6
13%
4
8.7%
1
2.1%
3
5.9%
M18:fellow eye, Losing >= 5 letters
10
21.7%
7
15.2%
4
8.3%
9
17.6%
M18:fellow eye, Losing <5
27
58.7%
24
52.2%
28
58.3%
30
58.8%
12. Secondary Outcome
Title Mean Change in ETDRS-BCVA Score From Baseline at Every Month up to Month 18
Description Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed as change from baseline in the mean best-corrected ETDRS visual acuity score at 18 months. Change from Baseline is defined as post-dose visit value minus Baseline value. Note that screening occurs before baseline. Values were truncated to one decimal place and negative sign retained where value is negative and the truncated value is zero. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Baseline and every month up to Month 18

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 46 48 51
Study eye, screening, n=46,46,48,48
0.2
(5.76)
2.6
(6.31)
0.6
(7.69)
0.1
(8.09)
Study eye, month 1, n=44,44,44,44
0.7
(4.77)
0.3
(5.13)
0.4
(5.02)
-1.3
(5.14)
Study eye, month 2, n=44,43,43,43
-0.3
(7.09)
1.0
(4.68)
1.2
(4.45)
-0.3
(6.38)
Study eye, month 3, n=43,37,42,42
0.0
(6.57)
0.5
(7.53)
1.0
(5.86)
-0.0
(6.39)
Study eye, month 4, n=43,36,42,42
0.9
(7.93)
1.6
(6.72)
0.3
(6.00)
-1.4
(8.09)
Study eye, month 5, n=43,36,39, 39
-1.2
(9.03)
0.5
(6.60)
2.2
(4.88)
-2.6
(9.36)
Study eye, month 6, n=43,36,40,40
-0.8
(9.90)
1.1
(6.91)
1.6
(6.55)
-1.0
(7.80)
Study eye, month 7, n=43,36,40,40
0.3
(10.49)
1.4
(7.04)
1.1
(8.35)
-1.7
(7.71)
Study eye, month 8, n=42,33,40,40
-0.0
(11.07)
1.5
(5.94)
0.6
(8.26)
-3.4
(8.87)
Study eye, month 9, n=41,33,40,40
-0.8
(10.90)
1.0
(5.97)
1.3
(7.39)
-2.2
(8.93)
Study eye, month 10, n=41,32,40,40
0.0
(11.12)
-0.6
(7.40)
0.7
(10.05)
-3.3
(9.86)
Study eye, month 11, n=41,33,40,40
0.4
(11.69)
0.1
(6.77)
-0.6
(8.87)
-4.1
(8.92)
Study eye, month 12, n=39,30,38,38
-1.3
(11.57)
-0.4
(6.12)
0.3
(9.94)
-4.4
(9.69)
Study eye, month 13, n=38,31,39,39
0.7
(8.21)
-0.1
(6.89)
-0.9
(9.93)
-4.2
(9.79)
Study eye, month 14, n=38,31,35,35
-1.3
(10.84)
-0.2
(8.12)
-1.2
(10.46)
-3.8
(9.68)
Study eye, month 15, n=37,31,35,35
-1.7
(11.13)
-1.7
(9.09)
-2.4
(11.33)
-4.0
(9.36)
Study eye, month 16, n=37,31,35,35
-0.6
(10.06)
-2.1
(8.71)
-2.2
(12.48)
-3.9
(9.83)
Study eye, month 17, n=38,32,36,36
-3.9
(14.56)
-1.9
(8.33)
-1.3
(11.85)
-3.9
(9.48)
Study eye, month 18, n=37,31,33,33
-3.0
(11.58)
-2.2
(10.61)
-3.6
(15.05)
-4.4
(9.72)
Fellow eye, screening, n=46,45,46,51
-0.0
(6.74)
1.0
(8.30)
0.7
(6.81)
0.4
(9.46)
Fellow eye, month 1, n=44,44,43,51
0.8
(5.01)
1.6
(6.22)
0.3
(5.52)
-0.8
(7.52)
Fellow eye, month 2, n=44,43,42,49
1.1
(5.61)
2.3
(7.21)
1.4
(5.50)
1.0
(8.86)
Fellow eye, month 3, n=43,37,41,46
1.8
(7.73)
2.3
(8.01)
1.2
(6.63)
2.0
(6.57)
Fellow eye, month 4, n=43,36,41,46
2.7
(8.32)
3.6
(7.80)
2.6
(7.95)
1.1
(6.63)
Fellow eye, month 5, n=43,36,38,46
2.4
(8.13)
3.6
(9.47)
1.5
(8.01)
1.8
(5.79)
Fellow eye, month 6, n=43,36,39,43
0.4
(11.62)
3.2
(8.81)
3.4
(6.55)
2.8
(7.66)
Fellow eye, month 7, n=43,36,39,44
0.4
(13.15)
3.5
(8.70)
3.3
(7.01)
1.9
(6.24)
Fellow eye, month 8, n=42,33,39,44
-0.4
(14.53)
3.2
(7.08)
1.2
(7.75)
2.6
(8.16)
Fellow eye, month 9, n=41,33,39,44
-0.8
(12.42)
4.5
(7.12)
2.7
(7.28)
3.0
(7.59)
Fellow eye, month 10, n=41, 32,39,44
-0.8
(14.22)
4.2
(7.58)
2.4
(8.61)
1.2
(9.26)
Fellow eye, month 11, n=41,33,39,42
0.1
(12.57)
2.5
(7.96)
1.0
(9.05)
2.7
(7.89)
Fellow eye, month 12, n=39,30,37,41
-0.9
(13.48)
3.2
(8.58)
2.7
(7.36)
0.5
(10.34)
Fellow eye, month 13, n=38,31,37,39
-0.2
(13.62)
3.7
(7.92)
1.8
(7.15)
2.1
(8.64)
Fellow eye, month 14, n=38,31,34,39
-0.3
(13.22)
1.8
(11.85)
2.9
(7.65)
1.9
(7.69)
Fellow eye, month 15, n=37,31,34,39
-1.2
(13.44)
1.7
(8.13)
2.3
(7.28)
2.3
(6.45)
Fellow eye, month 16, n=37,31,34,39
0.1
(12.27)
2.0
(9.42)
2.9
(8.42)
2.4
(7.88)
Fellow eye, month 17, n=38,32,35,40
-2.1
(13.53)
2.7
(9.55)
1.6
(9.32)
1.6
(8.58)
Fellow eye, month 18, n=37,31,32,39
-1.1
(13.12)
1.2
(10.01)
2.5
(8.98)
0.4
(8.04)
13. Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to the End of Dosing Interval at Steady-state (AUC0-28d) of GSK933776 in Geographic Atrophy Participants
Description Area under the plasma concentration-time curve from time 0 to the end of dosing interval at steady-state; derived from dose and clearance parameters was evaluated. Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.
Time Frame Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Parameter Population: all participants in the ITT Population with derived PK parameters
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 0 42 43 49
Geometric Mean (95% Confidence Interval) [microgram (mcg)*hours (h)/mL]
16725.96
29717.17
69485.24
14. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK933776 in Geographic Atrophy Participants
Description Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Time Frame Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Outcome Measure Data

Analysis Population Description
PK Parameter Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 0 42 43 49
Cmax
82311.15
142728.2
350716.9
Ctau
8551.70
15512.19
37589.25
15. Secondary Outcome
Title Clearance (CL) of GSK933776 in Geographic Atrophy Participants
Description Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.
Time Frame Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Outcome Measure Data

Analysis Population Description
PK Parameter Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 0 42 43 49
Geometric Mean (95% Confidence Interval) [mL/h]
14.66
14.90
16.09
16. Secondary Outcome
Title Estimation of Terminal Phase Half-life (T1/2) of GSK933776 in Geographic Atrophy Participants
Description Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.
Time Frame Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Outcome Measure Data

Analysis Population Description
PK Parameter Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 0 42 43 49
Geometric Mean (95% Confidence Interval) [Days]
11.67
11.87
11.27
17. Secondary Outcome
Title Volume of Distribution at Steady-state (Vdss) of GSK933776 in Geographic Atrophy Participants Estimated From Population PK Modeling
Description Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.
Time Frame Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Outcome Measure Data

Analysis Population Description
PK Parameter Population
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 0 42 43 49
Geometric Mean (95% Confidence Interval) [mL]
5618.72
5825.03
5959.42
18. Secondary Outcome
Title The Pharmacodynamic Effects of GSK933776 Total (Bound and Unbound) Plasma Total Amyloid Beta (Abeta42), and Amyloid Beta Fragments (Abeta18-35), if Possible, Unbound Plasma Aβ Fragments (Abeta1-22)
Description Blood samples were collected at the indicated time points on Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18

Outcome Measure Data

Analysis Population Description
PD Concentration Population: all participants in the ITT Population with at least one PD sample
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
Measure Participants 46 44 48 51
Ab1-22 Baseline, n=45,42,46,48
715.69
(237.06)
702.63
(278.771)
729.12
(260.094)
709.04
(205.697)
Ab1-22 month 3, PD, n=41,39,39, 46
675.95
(158.88)
833.22
(557.283)
721.04
(436.777)
756.85
(367.050)
Ab1-22, month 3, 1H post, n=40,39,36,44
706.74
(159.38)
101.59
(88.045)
86.57
(76.641)
73.29
(115.732)
Ab1-22, month 3, 3H post, n=40,39,37,43
707.00
(168.67)
142.63
(144.798)
92.22
(80.565)
67.42
(50.512)
Ab1-22, month 3, 7 D post M3, n=9,12,14,9
701.59
(232.76)
571.23
(445.822)
438.53
(270.154)
274.57
(190.397)
Ab1-22, month 3, 14 D post M3, n=9,9,6,14
825.32
(197.52)
587.33
(364.383)
357.47
(228.729)
444.97
(149.504)
Ab1-22, month 3, 21 D post M3, n=23,15, 18,22
592.13
(205.75)
669.63
(377.229)
730.61
(419.034)
674.38
(270.355)
Ab1-22 month 4, PD, n=39,32,39,44
671.16
(207.78)
798.93
(588.940)
763.67
(468.654)
811.97
(300.797)
Ab1-22, month 4, 1 H post, n=38,30,37,42
681.64
(245.28)
95.12
(101.607)
114.68
(142.473)
57.27
(33.590)
Ab1-22, month 4, 3 H post, n=38,31,35,41
713.41
(213.60)
113.68
(120.182)
104.79
(85.438)
64.05
(36.625)
Ab1-22 month 5, PD, n=38,29,38,46
686.71
(242.20)
876.62
(587.141)
725.24
(432.365)
829.03
(374.933)
Ab1-22, month 5, 1 H post, n=38,30,37,43
671.58
(263.41)
106.23
(117.776)
113.36
(114.519)
52.91
(31.684)
Ab1-22, month 5, 3 H post, n=38,29,36,43
680.31
(233.46)
131.86
(128.104)
99.54
(87.204)
93.08
(227.209)
Ab1-22 month 6, PD, n=36,31,35,45
664.05
(286.35)
944.83
(666.482)
786.00
(395.099)
796.74
(321.794)
Ab1-22, month 6, 1 H post, n=35,30,32,43
745.27
(262.59)
98.90
(89.639)
87.87
(76.150)
60.33
(45.976)
Ab1-22, month 6, 3 H post, n=36,30,31,43
717.93
(255.49)
127.41
(114.486)
101.20
(79.938)
93.26
(209.024)
Ab1-22 month 9, PD, n=38,28,34,42
698.54
(231.31)
965.46
(664.425)
731.34
(460.298)
710.63
(313.891)
Ab1-22, month 9, 1 H post, n=37,28,34,41
749.19
(230.82)
187.83
(206.605)
93.58
(103.359)
51.96
(33.876)
Ab1-22, month 9, 3 H post, n=37,26,34,40
706.89
(259.60)
172.30
(159.749)
101.28
(103.129)
54.65
(36.712)
Ab1-22 month 12, PD, n=38,30,37,41
688.50
(183.35)
980.25
(342.607)
724.92
(366.266)
669.94
(417.194)
Ab1-22, month 12, 1 H post, n=37,30,34,38
687.88
(203.57)
87.34
(74.521)
68.86
(77.852)
55.36
(46.136)
Ab1-22, month 12, 3 H post, n=37,31,31,37
680.21
(221.73)
162.41
(231.741)
79.92
(78.323)
56.04
(48.351)
Ab1-22 month 15, PD, n=36,27,31,39
667.13
(279.48)
1011.37
(458.087)
877.55
(589.463)
451.65
(310.992)
Ab1-22, month 15, 1 H post, n=38,28,32,38
674.94
(272.43)
102.84
(69.049)
92.10
(109.355)
52.10
(89.673)
Ab1-22, month 15, 3 H post, n=36,27,29,36
664.14
(321.47)
135.58
(78.565)
120.82
(124.908)
54.85
(76.984)
Ab1-22 month 18, PD, n=35,28,34,38
562.41
(186.57)
1019.37
(510.656)
968.23
(582.016)
396.39
(324.875)
Ab1-22, month 18, 1 H post, n=35,27,33,37
603.70
(184.05)
94.79
(54.323)
93.83
(77.725)
42.40
(37.672)
Ab1-22, month 18, 3 H post, n=34,26,32,37
572.09
(161.77)
127.62
(67.299)
103.38
(84.009)
38.60
(22.256)
Ab 18-34 Baseline, n=43,37,45,38
743.82
(380.653)
819.49
(296.673)
743.81
(406.171)
579.25
(277.483)
Ab 18-34 month 3, PD, n=39,38,37,45
785.65
(454.869)
18592.94
(5597.893)
27957.34
(8921.484)
33131.16
(11098.580)
Ab 18-34, month 3, 1H post, n=39,38,33,43
1408.61
(3774.763)
22652.19
(6213.219)
31669.84
(9225.846)
34207.81
(11060.95)
Ab 18-34, month 3, 3H post, n=37,38,32,43
836.20
(429.027)
26215.58
(7838.227)
34779.13
(9115.431)
38141.47
(9668.57)
Ab 18-34, month 3, 7 D post M3, n=7,11,11,8
922.92
(370.492)
44763.87
(6895.501)
56154.01
(13944.00)
49791.95
(16363.48)
Ab 18-34, month 3, 14 D post M3, n=9,11,4,14
1068.33
(779.813)
35763.55
(6062.090)
38729.93
(7646.892)
41809.21
(12065.52)
Ab 18-34, month 3, 21 D post M3, n=18,15,16,20
811.92
(321.961)
21020.41
(9021.023)
35400.30
(7979.633)
43914.27
(11231.62)
Ab 18-34 month 4, PD, n=35,31,35,
894.86
(443.914)
17268.05
(5857.907)
26716.77
(10948.73)
33334.70
(8458.286)
Ab 18-34, month 4, 1 H post, n=32,31,33,41
885.66
(377.125)
20994.88
(6978.372)
29940.66
(10073.83)
34964.84
(10002.35)
Ab 18-34, month 4, 3 H post, n=32,31,31,40
881.00
(347.112)
24894.01
(7706.804)
32626.1
(10801.42)
37516.27
(10955.53)
Ab 18-34 month 5, PD, n=33,28,35, 46
951.92
(516.887)
18728.68
(6760.913)
27358.59
(11742.90)
32652.34
(9462.231)
Ab 18-34, month 5, 1 H post, n=34,28,35,42
962.84
(490.933)
23681.97
(7190.390)
29660.64
(10276.52)
33182.12
(9115.903)
Ab 18-34, month 5, 3 H post, n=36,28,34,40
893.16
(485.544)
25711.80
(6767.509)
33735.73
(12433.44)
34169.47
(8984.387)
Ab 18-34 month 6, PD, n=34,29,35,45
838.42
(425.702)
18801.95
(7605.319)
30073.49
(11286.35)
32538.92
(8469.383)
Ab 18-34, month 6, 1 H post, n=33,28,33,43
1566.28
(4065.365)
22511.14
(7848.044)
33259.36
(10975.41)
34146.93
(10421.73)
Ab 18-34, month 6, 3 H post, n=32,29,32,42
846.19
(421.980)
26457.65
(7860.423)
37724.75
(12990.61)
37139.56
(12656.18)
Ab 18-34 month 9, PD, n=33,22,33,42
609.41
(329.151)
18187.69
(6942.978)
27101.57
(11334.69)
33653.88
(12115.89)
Ab 18-34, month 9, 1 H post, n=33,23,32,40
617.63
(339.050)
22315.06
(8256.360)
29347.65
(11567.85)
34807.59
(11458.57)
Ab 18-34, month 9, 3 H post, n=
1503.09
(4809.095)
26238.37
(8950.567)
31788.45
(12230.14)
37923.17
(13928.32)
Ab 18-34 month 12, PD, n=32,22,33,39
565.11
(269.418)
15213.11
(7350.114)
24193.39
(10117.95)
33105.49
(9358.291)
Ab 18-34, month 12, 1 H post, n=37,29,36,40
555.39
(296.989)
21439.13
(9174.242)
25724.20
(9073.725)
35273.76
(11497.23)
Ab 18-34, month 12, 3 H post, n=35,29,33,37
1532.25
(5463.999)
21295.72
(6471.001)
28771.21
(9392.402)
37831.60
(11953.37)
Unscheduled, n=0,0,0,1
NA
(NA)
NA
(NA)
NA
(NA)
18312.40
(NA)
Ab 18-34 month 15, PD, n=35,26,30,37
461.47
(414.780)
16852.93
(6707.423)
22121.87
(7510.438)
28887.86
(7891.499)
Ab 18-34, month 15, 1 H post, n=30,27,31,37
530.88
(392.825)
20158.76
(7147.691)
26219.44
(7873.201)
28914.08
(9757.638)
Ab 18-34, month 15, 3 H post, n=26,25,30,33
825.72
(1527.743)
23509.29
(9303.296)
29785.49
(9191.623)
31653.02
(8909.182)
Ab 18-34 month 18, PD, n=27,27,34,38
3144.40
(9209.436)
14266.65
(7931.78)
21134.85
(8638.106)
28107.98
(9780.376)
Ab 18-34, month 18, 1 H post, n=28,27,33,37
2988.76
(8357.739)
18503.81
(9250.829)
24124.61
(7723.055)
29913.96
(10878.95)
Ab 18-34, month 18, 3 H post, n=28,27,32,36
3144.44
(9129.569)
21691.51
(8999.993)
28580.63
(8684.780)
31441.25
(10084.47)
Ab42 Baseline, n=38,39,41,20
139.90
(173.673)
92.27
(79.938)
99.86
(85.958)
384.28
(760.175)
Ab42 month 3, PD, n=36,38,40, 37
167.67
(255.009)
988.18
(370.001)
1523.72
(662.292)
1689.03
(652.829)
Ab42, month 3, 1H post, n= 35,38,37,37
145.58
(230.115)
1152.92
(420.811)
1589.49
(629.616)
1778.93
(644.677)
Ab42, month 3, 3H post, n=36,38,38,35
207.98
(345.712)
1296.12
(438.252)
1672.97
(664.08)
1959.40
(707.293)
Ab42, month 3, 7 D post M3, n=9,11,15,6
77.61
(34.043)
1697.51
(401.839)
2022.63
(897.848)
2007.92
(673.666)
Ab42, month 3, 14 D post M3, n=8,11,6,9
244.51
(277.941)
1599.87
(373.006)
1608.36
(360.506)
1695.08
(234.094)
Ab42, month 3, 21 D post M3, n=18,14, 18,19
169.91
(368.921)
1015.81
(394.872)
1559.20
(469.99)
2096.98
(769.107)
Ab42 month 4, PD, n=35,33,39, 29
195.41
(331.409)
984.70
(329.701)
1381.96
(666.242)
1575.82
(606.059)
Ab42, month 4, 1 H post, n=33,33,36,30
202.80
(338.066)
1095.62
(348.452)
1541.21
(657.964)
1821.73
(817.436)
Ab42, month 4, 3 H post, n=35,32,33,30
201.34
(334.588)
1313.46
(457.509)
1714.54
(689.400)
1744.84
(768.485)
Ab42 month 5, PD, n=33,32,39,34
186.73
(316.028)
978.6
(403.364)
1422.10
(620.253)
1450.71
(599.032)
Ab42, month 5, 1 H post, n=33,32,40,32
182.94
(293.746)
1214.53
(409.266)
1526.11
(651.944)
1572.92
(565.403)
Ab42, month 5, 3 H post, n=32,31,39,31
177.67
(285.526)
1351.07
(416.735)
1755.13
(741.876)
1696.91
(708.505)
Ab42 month 6, PD, n=27,30,38,33
218.22
(418.144)
1074.00
(495.245)
1711.71
(1502.526)
1509.95
(425.854)
Ab42, month 6, 1 H post, n=29,30,36,32
233.29
(401.633)
1241.12
(528.261)
1835.47
(1447.740)
1613.65
(493.896)
Ab42, month 6, 3 H post, n=27,32,34,31
222.86
(435.218)
1421.14
(545.844)
2074.12
(1509.886)
1723.03
(790.928)
Ab42 month 9, PD, n=19,27,37,38
191.73
(243.600)
1049.44
(419.011)
1650.02
(1809.009)
1519.98
(842.690)
Ab42, month 9, 1 H post, n=18,27,35,38
179.70
(212.048)
1218.78
(390.582)
1723.09
(1521.428)
1591.82
(749.909)
Ab42, month 9, 3 H post, n=17,24,36,37
201.73
(238.311)
1420.29
(486.511)
1857.20
(1642.287)
1691.34
(854.596)
Ab42 month 12, PD, n=13,27,37,37
200.69
(265.476)
916.06
(451.841)
1253.07
(566.682)
1221.73
(504.928)
Ab42, month 12, 1 H post, n=14,26,33,34
190.76
(246.820)
1211.53
(488.773)
1383.67
(605.187)
1324.37
(598.120)
Ab42, month 12, 3 H post, n=15,27,30,34
193.7
(240.465)
1238.51
(478.369)
1489.97
(519.535)
1411.51
(593.534)
Ab42 month 15, PD, n=11,27,30,37
255.38
(510.410)
1022.33
(415.974)
1109.96
(467.439)
1157.26
(347.208)
Ab42, month 15, 1 H post, n=11,27,34,36
241.82
(469.544)
1181.69
(458.696)
1266.70
(430.670)
1172.10
(300.788)
Ab42, month 15, 3 H post, n=10,26,30,34
272.83
(524.796)
1360.57
(510.374)
1488.49
(479.831)
1257.99
(330.407)
Ab42 month 18, PD, n=8,29,29,36
127.77
(106.936)
722.52
(381.288)
997.11
(438.328)
1087.18
(270.541)
Ab42, month 18, 1 H post, n=10,28,29,35
119.29
(95.689)
900.42
(434.525)
1134.77
(439.660)
1205.27
(389.468)
Ab42, month 18, 3 H post, n=10,28,27,35
109.09
(88.111)
1024.30
(472.320)
1326.97
(491.829)
1254.63
(304.826)

Adverse Events

Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication up to approximately 21 months.
Adverse Event Reporting Description SAEs and non-serious AEs were collected in members of the ITT Population, comprised of participants that completed the observation period and Baseline visit, and were subsequently randomized to treatment and were administered at least one IV dose.
Arm/Group Title Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Arm/Group Description Participants received placebo (0.9 percent sodium chloride) by intravenous (IV) infusion every 28 days for 18 months. Participants received 3 milligram (mg)/kilogram (kg) GSK933776 by IV infusion every 28 days for 18 months. Participants received 6 mg/kg GSK933776 by IV infusion every 28 days for 18 months. Participants received 15 mg/kg GSK933776 by IV infusion every 28 days for 18 months.
All Cause Mortality
Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/46 (19.6%) 11/46 (23.9%) 9/48 (18.8%) 12/51 (23.5%)
Cardiac disorders
Cardiac failure congestive 0/46 (0%) 2/46 (4.3%) 0/48 (0%) 0/51 (0%)
Aortic valve stenosis 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Coronary ostial stenosis 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Myocardial infarction 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Subendocardial ischaemia 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Ventricular asystole 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Ear and labyrinth disorders
vertigo 0/46 (0%) 0/46 (0%) 0/48 (0%) 2/51 (3.9%)
Eye disorders
Visual acuity reduced 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Gastrointestinal disorders
Crohn's disease 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Small intestinal obstruction 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Vomiting 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
General disorders
Asthenia 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Chest pain 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Gait disturbance 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Hepatobiliary disorders
Hepatic mass 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Infections and infestations
Pneumonia 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 2/51 (3.9%)
Urinary tract infection 0/46 (0%) 2/46 (4.3%) 0/48 (0%) 0/51 (0%)
Cholecystitis infective 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Liver abscess 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Lung infection 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Pharyngitis 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Pyelonephritis 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Sepsis 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Urosepsis 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Injury, poisoning and procedural complications
Road traffic accident 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Spinal compression fracture 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Metabolism and nutrition disorders
Hyponatraemia 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Osteoarthritis 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Gallbladder cancer 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Invasive ductal breast carcinoma 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Metastatic squamous cell carcinoma 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Ovarian cancer 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Squamous cell carcinoma of lung 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Nervous system disorders
Cerebellar infarction 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Cerebral haemorrhage 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Cerebrovascular accident 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Dementia 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Dizziness 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Lacunar infarction 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Syncope 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Toxic encephalopathy 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Renal and urinary disorders
Nephrolithiasis 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Renal colic 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Ureterolithiasis 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 1/46 (2.2%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Chronic obstructive pulmonary disease 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Dyspnoea 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Respiratory failure 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 0/51 (0%)
Vascular disorders
Aortic aneurysm 0/46 (0%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Hypertension 1/46 (2.2%) 0/46 (0%) 0/48 (0%) 0/51 (0%)
Orthostatic hypertension 0/46 (0%) 1/46 (2.2%) 0/48 (0%) 0/51 (0%)
Other (Not Including Serious) Adverse Events
Placebo GSK933776 (3 mg/kg) GSK933776 (6 mg/kg) GSK933776 (15 mg/kg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 31/46 (67.4%) 37/46 (80.4%) 32/48 (66.7%) 37/51 (72.5%)
Blood and lymphatic system disorders
Anaemia 0/46 (0%) 3/46 (6.5%) 2/48 (4.2%) 0/51 (0%)
Cardiac disorders
Ventricular extrasystoles 0/46 (0%) 2/46 (4.3%) 2/48 (4.2%) 3/51 (5.9%)
Atrial fibrillation 0/46 (0%) 3/46 (6.5%) 1/48 (2.1%) 1/51 (2%)
Eye disorders
Retinal haemorrhage 3/46 (6.5%) 4/46 (8.7%) 3/48 (6.3%) 4/51 (7.8%)
Blepharitis 2/46 (4.3%) 5/46 (10.9%) 4/48 (8.3%) 1/51 (2%)
Visual acuity reduced 2/46 (4.3%) 3/46 (6.5%) 1/48 (2.1%) 1/51 (2%)
Vitreous detachment 1/46 (2.2%) 3/46 (6.5%) 1/48 (2.1%) 1/51 (2%)
Macular fibrosis 0/46 (0%) 0/46 (0%) 1/48 (2.1%) 3/51 (5.9%)
Gastrointestinal disorders
Nausea 2/46 (4.3%) 4/46 (8.7%) 1/48 (2.1%) 4/51 (7.8%)
Diarrhoea 0/46 (0%) 3/46 (6.5%) 1/48 (2.1%) 4/51 (7.8%)
Vomiting 3/46 (6.5%) 0/46 (0%) 1/48 (2.1%) 2/51 (3.9%)
General disorders
Oedema peripheral 2/46 (4.3%) 3/46 (6.5%) 1/48 (2.1%) 4/51 (7.8%)
Peripheral swelling 3/46 (6.5%) 1/46 (2.2%) 0/48 (0%) 2/51 (3.9%)
Fatigue 0/46 (0%) 3/46 (6.5%) 2/48 (4.2%) 0/51 (0%)
Oedema 0/46 (0%) 3/46 (6.5%) 1/48 (2.1%) 0/51 (0%)
Pyrexia 0/46 (0%) 3/46 (6.5%) 0/48 (0%) 0/51 (0%)
Immune system disorders
Seasonal allergy 0/46 (0%) 0/46 (0%) 3/48 (6.3%) 0/51 (0%)
Infections and infestations
Urinary tract infection 3/46 (6.5%) 6/46 (13%) 4/48 (8.3%) 1/51 (2%)
Bronchitis 5/46 (10.9%) 2/46 (4.3%) 2/48 (4.2%) 3/51 (5.9%)
Sinusitis 6/46 (13%) 1/46 (2.2%) 1/48 (2.1%) 3/51 (5.9%)
Nasopharyngitis 3/46 (6.5%) 3/46 (6.5%) 1/48 (2.1%) 3/51 (5.9%)
Upper respiratory tract infection 3/46 (6.5%) 3/46 (6.5%) 0/48 (0%) 1/51 (2%)
Injury, poisoning and procedural complications
Contusion 2/46 (4.3%) 0/46 (0%) 1/48 (2.1%) 4/51 (7.8%)
Fall 1/46 (2.2%) 1/46 (2.2%) 0/48 (0%) 4/51 (7.8%)
Tooth fracture 1/46 (2.2%) 1/46 (2.2%) 0/48 (0%) 3/51 (5.9%)
Investigations
Cardiac murmur 1/46 (2.2%) 4/46 (8.7%) 1/48 (2.1%) 1/51 (2%)
Metabolism and nutrition disorders
Hyperlipidaemia 0/46 (0%) 1/46 (2.2%) 3/48 (6.3%) 1/51 (2%)
Musculoskeletal and connective tissue disorders
Back pain 1/46 (2.2%) 4/46 (8.7%) 0/48 (0%) 5/51 (9.8%)
Arthralgia 1/46 (2.2%) 5/46 (10.9%) 1/48 (2.1%) 2/51 (3.9%)
Pain in extremity 1/46 (2.2%) 1/46 (2.2%) 0/48 (0%) 3/51 (5.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma 1/46 (2.2%) 3/46 (6.5%) 1/48 (2.1%) 3/51 (5.9%)
Squamous cell carcinoma of skin 3/46 (6.5%) 1/46 (2.2%) 0/48 (0%) 1/51 (2%)
Nervous system disorders
Headache 1/46 (2.2%) 4/46 (8.7%) 4/48 (8.3%) 3/51 (5.9%)
Dizziness 2/46 (4.3%) 3/46 (6.5%) 3/48 (6.3%) 2/51 (3.9%)
Nerve compression 0/46 (0%) 3/46 (6.5%) 1/48 (2.1%) 1/51 (2%)
Paraesthesia 0/46 (0%) 3/46 (6.5%) 0/48 (0%) 0/51 (0%)
Psychiatric disorders
Depression 4/46 (8.7%) 0/46 (0%) 2/48 (4.2%) 2/51 (3.9%)
Insomnia 3/46 (6.5%) 0/46 (0%) 0/48 (0%) 1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Cough 1/46 (2.2%) 3/46 (6.5%) 1/48 (2.1%) 0/51 (0%)
Sinus congestion 0/46 (0%) 3/46 (6.5%) 0/48 (0%) 1/51 (2%)
Skin and subcutaneous tissue disorders
Rash 0/46 (0%) 4/46 (8.7%) 0/48 (0%) 1/51 (2%)
Vascular disorders
Hypertension 2/46 (4.3%) 2/46 (4.3%) 4/48 (8.3%) 3/51 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01342926
Other Study ID Numbers:
  • 114341
First Posted:
Apr 27, 2011
Last Update Posted:
May 5, 2017
Last Verified:
Mar 1, 2017