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Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects

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ClinicalTrials.gov Identifier: NCT03965533
Recruitment Status : Completed
First Posted : May 29, 2019
Results First Posted : November 18, 2020
Last Update Posted : November 18, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Healthy Volunteers
Interventions Drug: GSK2831781
Drug: Placebo
Enrollment 36
Recruitment Details This was a double-blind, placebo-controlled, randomized, parallel group, two-part study to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) dose of GSK2831781 in healthy Japanese and Caucasian participants (Part A) and subcutaneous (SC) dose of GSK2831781 in healthy Caucasian participants (Part B).
Pre-assignment Details A total of 30 participants were screened and 16 participants were enrolled in Part A (14 were screen failures). A total of 41 participants were screened and 20 participants were enrolled in Part B (21 were screen failures). Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo. Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline. Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo. Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo. Arm Description: Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Period Title: Part A (112 Days)
Started 2 6 2 6 0 0 0
Completed 2 6 2 6 0 0 0
Not Completed 0 0 0 0 0 0 0
Period Title: Part B (112 Days)
Started 0 0 0 0 4 8 8
Completed 0 0 0 0 4 8 8
Not Completed 0 0 0 0 0 0 0
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC Total
Hide Arm/Group Description Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo. Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline. Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo. Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo. Arm Description: Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg. Total of all reporting groups
Overall Number of Baseline Participants 2 6 2 6 4 8 8 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 6 participants 2 participants 6 participants 4 participants 8 participants 8 participants 36 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
 100.0%
6
 100.0%
2
 100.0%
6
 100.0%
4
 100.0%
8
 100.0%
8
 100.0%
36
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 6 participants 2 participants 6 participants 4 participants 8 participants 8 participants 36 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
2
 100.0%
6
 100.0%
2
 100.0%
6
 100.0%
4
 100.0%
8
 100.0%
8
 100.0%
36
 100.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 6 participants 2 participants 6 participants 4 participants 8 participants 8 participants 36 participants
White-White/Caucasian/European Heritage (H)
2
 100.0%
6
 100.0%
0
   0.0%
0
   0.0%
4
 100.0%
8
 100.0%
8
 100.0%
28
  77.8%
Asian-Japanese H/East Asian H/South East Asian H
0
   0.0%
0
   0.0%
2
 100.0%
6
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
8
  22.2%
1.Primary Outcome
Title Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)
Hide Description An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprised of all randomized (all participants who were randomized into the study and received a randomization number) participants who received study intervention.
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
Non-SAEs
2
 100.0%
5
  83.3%
0
   0.0%
4
  66.7%
SAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Part B: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)
Hide Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants who had SAEs and non-SAEs are presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
Non-SAEs
4
 100.0%
6
  75.0%
4
  50.0%
SAEs
0
   0.0%
1
  12.5%
0
   0.0%
3.Primary Outcome
Title Part A: Number of Participants With Vital Signs of Potential Clinical Importance
Hide Description Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. The clinical concern range for the parameters were: SBP (low: <85 millimeters of mercury [mmHg] and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg), heart rate (low: <40 beats per minute [bpm] and high: >110 bpm) and temperature (low: <35 degrees celsius [°C] and high: >=37.5 °C). Number of participants with any vital sign value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Part B: Number of Participants With Vital Signs of Potential Clinical Importance
Hide Description Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, SBP, DBP and heart rate. The clinical concern range for the parameters were: SBP (low: <85 mmHg and high: >160 mmHg), DBP (low: <45 mmHg and high: >100 mmHg), heart rate (low: <40 bpm and high: >110 bpm) and temperature (low: <35 °C and high: >=37.5 °C). Number of participants with any vital sign value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
1
  25.0%
0
   0.0%
1
  12.5%
5.Primary Outcome
Title Part A: Number of Participants With Any Hematology Parameter of Potential Clinical Importance
Hide Description Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from Baseline <0.075 proportion of red cells in blood); hemoglobin (high: >180 grams per liter [g/L] and low: change from Baseline <25 g/L), lymphocytes (low: <0.8 Giga cells per liter [Giga cells/L]); neutrophil count (low: <1.5 Giga cells/L); eosinophil count (high: >1 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L) and white blood cells count (low: <3 Giga cells/L and high: >20 Giga cells/L). Number of participants with any hematology parameter value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  16.7%
0
   0.0%
2
  33.3%
6.Primary Outcome
Title Part B: Number of Participants With Any Hematology Parameter of Potential Clinical Importance
Hide Description Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from Baseline <0.075 proportion of red cells in blood); hemoglobin (high: >180 g/L and low: change from Baseline <25 g/L), lymphocytes (low: <0.8 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); eosinophil count (high: >1 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L) and white blood cells count (low: <3 Giga cells/L and high: >20 Giga cells/L). Number of participants with any hematology parameter value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  12.5%
7.Primary Outcome
Title Part A: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance
Hide Description Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: alanine aminotransferase (high: >=2 times upper limit of normal [ULN]); aspartate aminotransferase (high: >=2 times ULN); alkaline phosphatase (high: >=2 times ULN); total bilirubin (high: >=1.5 times ULN); blood urea nitrogen (high: >10.5 millimoles per liter [mmol/L]); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >26 micromoles per liter); estimated glomerular filtration rate (low: <60 milliliter per minute per 1.73 squared meter); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and total protein (low: <50 g/L and high: >85 g/L). Number of participants with any clinical chemistry parameter value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
8.Primary Outcome
Title Part B: Number of Participants With Any Clinical Chemistry Parameter of Potential Clinical Importance
Hide Description Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: alanine aminotransferase (high: >=2 times ULN); aspartate aminotransferase (high: >=2 times ULN); alkaline phosphatase (high: >=2 times ULN); total bilirubin (high: >=1.5 times ULN); blood urea nitrogen (high: >10.5 mmol/L]); calcium (low: <2 mmol/L and high: >2.75 mmol/L); creatinine (high: change from Baseline >26 micromoles per liter); estimated glomerular filtration rate (low: <60 milliliter per minute per 1.73 squared meter); glucose (low: <3 mmol/L and high: >9 mmol/L); potassium (low: <3 mmol/L and high: >5.5 mmol/L); sodium (low: <130 mmol/L and high: >150 mmol/L) and total protein (low: <50 g/L and high: >85 g/L). Number of participants with any clinical chemistry parameter value of potential clinical importance is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  12.5%
9.Primary Outcome
Title Part A: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance (PCI)
Hide Description Urine samples were analyzed for bilirubin (Bil.),glucose (Gl.),ketones (Keto),leukocytes (leuko),nitrite (Nit.),occult blood (OB) and protein (Pro.) by dipstick method. Urine red blood cells (RBC) and white blood cells (WBC) were assessed by microscopy. Urine potential of hydrogen (pH) and specific gravity (Sp.Gr.) were also analyzed. The dipstick results are read as Trace,1+,2+ indicating proportional concentrations. pH is measured on a numeric scale of 0 to 14 (pH 7: neutral, pH <7: acidic and pH >7: basic). Urine Sp. Gr. is a measure of the concentration of solutes in the urine and indicated as ratio of urine density to water density. The clinical concern range for these parameters were: Bil., Gl., Leuko, OB and Pro. (high: >1+),Keto (high: >2+),Nit. (high: positive),pH (low: <4.6 and high: >8),Sp.Gr. (low: <1.001 and high: >1.035),RBC (high: >3 cells/high power field [hpf]) and WBC (high: >5 cells/hpf). Number of participants with any urinalysis parameter value of PCI is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
2
 100.0%
0
   0.0%
0
   0.0%
1
  16.7%
10.Primary Outcome
Title Part B: Number of Participants With Any Urinalysis Parameter of Potential Clinical Importance
Hide Description Urine samples were analyzed for Bil., Gl., Keto, leuko, Nit., OB and Pro. by dipstick method. Urine RBC and WBC were assessed by microscopy. Urine pH and Sp.Gr. were also analyzed. The dipstick results are read as Trace, 1+, 2+ indicating proportional concentrations. pH is measured on a numeric scale of 0 to 14 (pH 7: neutral, pH <7: acidic and pH >7: basic). Urine Sp. Gr. is a measure of the concentration of solutes in the urine and indicated as ratio of urine density to water density. The clinical concern range for these parameters were: Bil., Gl., Leuko, OB and Pro. (high: >1+), Keto (high: >2+), Nit. (high: positive), pH (low: <4.6 and high: >8), Sp.Gr. (low: <1.001 and high: >1.035), RBC (high: >3 cells/hpf) and WBC (high: >5 cells/hpf). Number of participants with any urinalysis parameter value of PCI is reported.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
1
  25.0%
0
   0.0%
0
   0.0%
11.Primary Outcome
Title Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description Twelve-lead ECGs were recorded with the participants in a semi-supine position, after 5 minutes of rest using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
Abnormal-not Clinically significant
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal-Clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
12.Primary Outcome
Title Part B: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description Twelve-lead ECGs were recorded with the participants in a semi-supine position, after 5 minutes of rest using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
Abnormal-not Clinically significant
0
   0.0%
1
  12.5%
0
   0.0%
Abnormal-Clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
13.Primary Outcome
Title Part A: Number of Participants With Injection Site Reaction
Hide Description Local tolerability as measured by injection site reaction example; bruise at the site of injection and/or itching, pain, blistering or skin damage. Number of participants with any injection site reaction are presented.
Time Frame Up to 24 hours (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2
  33.3%
14.Primary Outcome
Title Part B: Number of Participants With Injection Site Reaction
Hide Description Local tolerability as measured by injection site reaction example; bruise at the site of injection and/or itching, pain, blistering or skin damage. Number of participants with any injection site reaction are presented.
Time Frame Up to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Part A: Area Under the Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK2831781 Following IV Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population comprised of all safety participants for whom a pharmacokinetic sample was obtained and analyzed.
Arm/Group Title Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*micrograms per milliliter
44261.755
(23.8009%)
49650.933
(19.6053%)
16.Secondary Outcome
Title Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2831781 Following IV Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per milliliter
137.61
(22.449%)
166.20
(20.428%)
17.Secondary Outcome
Title Part A: Time to Maximum Observed Plasma Concentration (Tmax) of GSK2831781 Following IV Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 6 6
Median (Full Range)
Unit of Measure: Hours
1.980
(1.98 to 2.17)
1.990
(1.95 to 6.02)
18.Secondary Outcome
Title Part B: AUC(0 to t) of GSK2831781 Following SC Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*micrograms per milliliter
6633.227
(26.6369%)
24269.036
(40.4247%)
19.Secondary Outcome
Title Part B: Cmax of GSK2831781 Following SC Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per milliliter
14.61
(30.229%)
41.13
(34.252%)
20.Secondary Outcome
Title Part B: Tmax of GSK2831781 Following SC Dose
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time Frame Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 8 8
Median (Full Range)
Unit of Measure: Hours
95.750
(46.92 to 167.75)
120.270
(69.72 to 169.73)
21.Secondary Outcome
Title Part A and Part B: Bioavailability (F) of GSK2831781 Following IV Dosing at 450 mg (Caucasian and Japanese Participants) or SC Dosing at 150 mg and 450 mg (Caucasian Participants)
Hide Description Blood samples were collected at indicated time points for pharmacokinetic analysis in Part A (IV dose) and Part B (SC doses). Bioavailability of GSK2831781 was estimated by fitting a population pharmacokinetic model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and total soluble lymphocyte activation gene-3 (LAG3) concentrations in serum and was expressed as a percentage.
Time Frame Part A (IV): Day 1 (Pre-dose and 1, 2, 6, 12, 24 hours post-dose); Days 3, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 112; Part B (SC): Day 1 (Pre-dose); Days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 57, 71, 85 and 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the non-linearity in pharmacokinetics, a population pharmacokinetic analysis of pooled data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on pooled data from Part A and Part B.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage Bioavailability
76.5
(76.5 to 76.5)
22.Secondary Outcome
Title Degradation Rate of LAG3 Positive T Cells (Kout) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and Part B)
Hide Description Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) pharmacokinetic/pharmacodynamic (PK/PD) model. Kout was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; Kout is presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on combined data from Part A and Part B.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Per hour
0.0256
(0.0161 to 0.0405)
23.Secondary Outcome
Title Baseline of LAG3 Positive T Cell Count (CELL0) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)
Hide Description Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. CELL0 was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; CELL0 is presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on combined data from Part A and Part B.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Cells per microliter
1.15
(1.11 to 1.19)
24.Secondary Outcome
Title Concentration of Free GSK2831781 at Which Half Maximum Effect on Kout is Achieved (EC50) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)
Hide Description Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. EC50 was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. As there was a limited dose range, to allow for a successful model conversion, EC50 was fixed to the EC50 value estimated from a previous study. The model parameter; EC50 is presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. This outcome measure was fixed to the EC50 value estimated from a previous study.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Nanograms per milliliter
9509
(174 to 540000)
25.Secondary Outcome
Title Maximum Effect of Change in Kout (Emax) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)
Hide Description Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. Emax, a unitless parameter that describes the maximum change in Kout at infinite GSK2831781 concentration, was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; Emax is presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on combined data from Part A and Part B.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Unitless
2.35
(1.90 to 2.90)
26.Secondary Outcome
Title Hill Coefficient (GAM) Derived From Statistical Analysis of the Relationship Between LAG3 Positive T Cell Levels in Blood and GSK2831781 Concentrations in Plasma (Part A and B)
Hide Description Blood samples were collected to measure LAG3 positive T cell levels. Plasma samples were collected to measure concentrations of GSK2831781 in plasma. The relationship between the pharmacodynamic measure (LAG3 positive T cell levels in blood) and plasma concentrations of GSK2831781 was described by an indirect response (Emax type) PK/PD model. The Hill coefficient GAM, a unitless parameter defining the steepness of the concentration-effect curve, was calculated by fitting the PK/PD model to all available data (Part A and Part B) of GSK2831781 concentrations in plasma and LAG3 positive T cells in blood. The model parameter; GAM is presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population. Given the limited dose range (150 mg-450 mg) in each part, a population PK/PD analysis of combined data from Part A and Part B was more appropriate. Hence, this outcome measure was estimated on combined data from Part A and Part B.
Arm/Group Title Part A and Part B: All Participants
Hide Arm/Group Description:
In Part A, Caucasian and Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. In Part B, Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per mL of GSK2831781, diluted in 0.9% w/v saline and also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. To achieve a dose of 450 mg, Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Unitless
0.0942
(0.0453 to 0.196)
27.Secondary Outcome
Title Part A: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result
Hide Description Serum samples were analyzed for the presence of anti-GSK2831781 antibodies using a validated immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'confirmed positive'. Number of participants with confirmed positive post-Baseline ADA result are presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants
Hide Arm/Group Description:
Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo.
Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline.
Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo.
Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline.
Overall Number of Participants Analyzed 2 6 2 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
28.Secondary Outcome
Title Part B: Number of Participants With Confirmed Positive Post-Baseline Anti-drug Antibody Result
Hide Description Serum samples were analyzed for the presence of anti-GSK2831781 antibodies using a validated immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'confirmed positive'. Number of participants with confirmed positive post-Baseline ADA result are presented.
Time Frame Up to Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Placebo arms across similar dosing strategies were combined in Part B.
Arm/Group Title Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description:
Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo.
Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding.
Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
Overall Number of Participants Analyzed 4 8 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) up to Day 112 in Part A and in Part B
Adverse Event Reporting Description SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received study intervention. Placebo arms across similar dosing strategies were combined in Part B.
 
Arm/Group Title Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Hide Arm/Group Description Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo. Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline. Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo. Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo. Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.
All-Cause Mortality
Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   0/6 (0.00%)   0/2 (0.00%)   0/6 (0.00%)   0/4 (0.00%)   0/8 (0.00%)   0/8 (0.00%) 
Hide Serious Adverse Events
Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   0/6 (0.00%)   0/2 (0.00%)   0/6 (0.00%)   0/4 (0.00%)   1/8 (12.50%)   0/8 (0.00%) 
Infections and infestations               
Tonsillitis  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part A: Placebo IV- Caucasian Participants Part A: GSK2831781 450 mg IV- Caucasian Participants Part A: Placebo IV- Japanese Participants Part A: GSK2831781 450 mg IV- Japanese Participants Part B: Placebo SC Part B: GSK2831781 150 mg SC Part B: GSK2831781 450 mg SC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   5/6 (83.33%)   0/2 (0.00%)   4/6 (66.67%)   4/4 (100.00%)   6/8 (75.00%)   4/8 (50.00%) 
Gastrointestinal disorders               
Toothache  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
General disorders               
Injection site bruising  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  2/6 (33.33%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Catheter site bruise  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Fatigue  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Injection site erythema  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Vessel puncture site bruise  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pain  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Infections and infestations               
Nasopharyngitis  1  0/2 (0.00%)  2/6 (33.33%)  0/2 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  2/8 (25.00%)  1/8 (12.50%) 
Cellulitis  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
Tooth infection  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications               
Arthropod bite  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Musculoskeletal and connective tissue disorders               
Back pain  1  1/2 (50.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Musculoskeletal pain  1  1/2 (50.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Myalgia  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Arthralgia  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Nervous system disorders               
Headache  1  1/2 (50.00%)  2/6 (33.33%)  0/2 (0.00%)  2/6 (33.33%)  0/4 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Paraesthesia  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Psychiatric disorders               
Anxiety  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders               
Nocturia  1  1/2 (50.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  0/2 (0.00%)  2/6 (33.33%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Oropharyngeal pain  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/8 (12.50%)  1/8 (12.50%) 
Rhinorrhoea  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nasal congestion  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
Sneezing  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders               
Rash  1  0/2 (0.00%)  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Dry skin  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
Ecchymosis  1  0/2 (0.00%)  0/6 (0.00%)  0/2 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/8 (0.00%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03965533    
Other Study ID Numbers: 207823
First Submitted: May 24, 2019
First Posted: May 29, 2019
Results First Submitted: October 23, 2020
Results First Posted: November 18, 2020
Last Update Posted: November 18, 2020