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| Name | Class |
|---|---|
| Quintiles, Inc. | INDUSTRY |
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This study is intended to enable a possible transition to intramuscular (IM) or subcutaneous (SQ) administration for subsequent studies with GSK933776 by characterizing the safety, tolerability, PK and pharmacodynamic profiles, and immunogenicity of GSK933776 following IM and SQ administration in healthy volunteers. Such alternate routes of administration may provide more options in the selection of an efficacious dose for subsequent development in patients with geographic atrophy. There will be four treatment arms in the study and participants will be assigned to 1 of 4 possible treatment arms in a 1:1:1:1 ratio. The planned number of evaluable participants for this study is 24 with 6 participants completing all critical assessments in each of the four treatment arms. The total duration of participation from screening to follow-up for Treatment Arms A, B and D (single dose of GSK933776), will be approximately 113 days and total duration for Treatment Arm C (repeat dose of GSK933776) will be approximately 134 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Active Comparator | Participants in this arm will receive single 200 milligram (mg) dose of GSK933776 administered by IV infusion |
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| Arm B | Experimental | Participants in this arm will receive single 200 mg dose of GSK933776 administered SQ |
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| Arm C | Experimental | Participants in this arm will receive 50 mg dose of GSK933776 administered SQ once weekly for 4 weeks (total dose = 200 mg). |
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| Arm D | Experimental | Participants in this arm will receive single 200 mg dose of GSK933776 administered IM |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK933776 for SQ administration | Drug | Antibody solution for subcutaneous injection with unit dose strength of 50mg/mL administered as 200 mg single dose or as repeat dose of 50 mg weekly for 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Relative bioavailability of GSK933776 after single dose SQ or IM administration as compared to IV infusion | Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of area under concentration time curve from time zero to infinity (AUC [0-infinity]) following single dose SQ and IM injection to intravenous (IV) infusion | Blood samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose |
| Relative bioavailability of GSK933776 after repeat dose SQ administration as compared to IV infusion | Bioavailability is defined as the rate and extent to which drug reaches the systemic circulation. The relative bioavailability will be calculated from the ratio of AUC (0-infinity) following SQ repeat dose injections to intravenous (IV) infusion | Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters of GSK933776 following single dose IM and SQ administration as compared to IV administration | PK parameters include: area under the concentration-time curve over the dosing interval (AUC[0-tau]), maximum concentration (Cmax), time of occurrence of Cmax (Tmax), terminal phase half-life (T1/2), clearance, and volume of distribution as data permit | Samples will be collected at following time points: pre-dose and at (0.25, 0.5, 0.75, 1, 2, 4 hours only for IV infusion), 6, 24, 48, 72, 96, 120, 216, 336, 504, 672, 1344 and 2016 hours post dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| Results for study 116891 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116891 | Statistical Analysis Plan | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| ID | Term |
|---|---|
| D057092 | Geographic Atrophy |
| D058225 | Plaque, Amyloid |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D009934 | Organization and Administration |
| ID | Term |
|---|---|
| D006298 | Health Services Administration |
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| GSK933776 for IM administration | Drug | Antibody solution for intramuscular injection with unit dose strength of 50mg/mL administered as 200 mg single dose |
|
| GSK933776 for IV administration | Drug | Antibody solution for intravenous injection with unit dose strength of 50mg/mL administered as 200 mg single dose through an IV catheter over approximately 1 hour |
|
| Composite of PK parameters of GSK933776 following repeat dose SQ administration as compared to IV administration | PK parameters include: AUC(0-tau), Cmax, Tmax, T1/2, clearance, and volume of distribution as data permit | Blood samples will be collected at following time points: pre-dose, 6, 24, 48, 72, 96 and 120 hours post dose in each of the 4 dosing weeks and additionally at 216, 336, 504, 672, 1344 and 2016 hours post last dose. |
| Number of participants with adverse events as a measure of safety and tolerability following single dose administration | AEs will be collected from the start of Study Treatment and until the follow-up contact | Up to 113 days |
| Clinical observation following IV, SQ and IM single dose administration as a measure of safety and tolerability | AEs will be collected from the start of Study Treatment and until the follow-up contact | Up to 134 days |
| Clinical observation following IV, SQ and IM repeat dose administration as a measure of safety and tolerability | Clinical observation include: physical examination, medical history, and review of concomitant medication | Up to 113 days |
| Vital sign measurement following single dose administration as a measure of safety and tolerability | Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement. | Up to 134 days |
| Vital sign measurement following repeat dose administration as a measure of safety and tolerability | Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and body temperature measurement. | Up to 134 days |
| Electrocardiogram (ECG) measurement following single dose administration to assess safety and tolerability | 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc interval). | Up to 113 days |
| ECG measurement following repeat dose administration to assess safety and tolerability | 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc interval. | Up to 134 days |
| Clinical laboratory parameters assessment following single dose administration as a measure of safety and tolerability | Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters. | Up to 113 days |
| Clinical laboratory parameters assessment following repeat dose administration as a measure of safety and tolerability | Clinical laboratory assessment include: hematology, clinical chemistry, urinalysis and additional parameters. | Up to 134 days |
| Plasma concentrations of GSK933776, total amyloid beta (AB), total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following single dose administrationof GSK933776 | The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit | Up to 113 days |
| Plasma concentration of GSK933776, AB, total AB fragments, as well as unbound concentrations of AB, fragments containing the epitope 1-22, as data permit following repeat dose administration | The relationship between plasma concentration of GSK933776 and plasma concentration of total and free amyloid beta will be explored as data permit | Up to 134 days |
| Presence of antibodies to GSK933776 in serum samples following single dose administration of GSK933776 | To characterize the immunogenicity profile of GSK933776 following IV, IM and SQ administration. Samples will be analyzed for the presence of anti-GSK933776 antibodies by immuno-electrochemiluminescent (ECL) screening and neutralization assays. | Up to 113 days |
| Presence of antibodies to GSK933776 in serum samples following repeat dose administration | To characterize the immunogenicity profile of GSK933776 following IV, IM and SQ administration. Samples will be analyzed for the presence of anti-GSK933776 antibodies by immuno-electrochemiluminescent (ECL) screening and neutralization assays. | Up to 134 days |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116891 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |