First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect

NCT03627494 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 209275
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The FTIH study with GSK3439171A will evaluate the safety of GSK3439171A in healthy subjects in order to avoid confounding factors due to the disease or concomitant drugs in patients. The study design is based on pre-clinical findings for GSK3439171A, contributing to the frequency, type and duration of safety assessment and monitoring during treatment periods in each cohort. The single dose assessments in Part A will be conducted to determine safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the study intervention in individuals before progressing to doses explored further in other parts of the study and will allow for any adjustments needed based on emerging safety, tolerability, and PK information. Part A will also serve to identify a dose for use in examining the effect of food on GSK3439171A exposure in Part C. In Part B, a single dose safety, tolerability and PK will be collected followed by progression of these subjects to the repeat dose portion of the study. The up to 14-day dosing was chosen as it is thought to provide sufficient safety and tolerability data to bridge to longer duration studies. The dosing period can be adjusted depending on PK and PD data collected in Part A of the study. Part B will involve more detailed PK/PD/metabolite assessments to better understand the impact of GSK3439171A on target engagement and metabolism in humans. Approximately 150 subjects will be screened to achieve 75 randomly assigned to study intervention. Duration for Part A, B and C will be approximately 10 weeks, 9 weeks and 8 weeks respectively.

Conditions

Muscular Dystrophies

Keywords

Dose proportionality; Food effect; Pharmacokinetics; FTIH; Pharmacodynamics; Dose Escalation

Outcome Measures

Primary Outcomes (51)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  Up to Day 40

• Number of Participants With AEs and SAEs-Part B

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  Up to Day 34

• Number of Participants With AEs and SAEs-Part C

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  Up to Day 29

• Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part A

  Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 grams per liter \[g/L\]); alanine aminotransferase (ALT) (high: \>=2xupper limit of normal \[ULN\]); aspartate aminotransferase (AST) (high: \>=2xULN); alkaline phosphatase (ALP) (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 millimoles (mmol)/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  Up to Day 40

• Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part B

  Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 g/L); ALT (high: \>=2xULN); AST (high: \>=2xULN); ALP (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  Up to Day 34

• Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part C

  Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 g/L); ALT (high: \>=2xULN); AST (high: \>=2xULN); ALP (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.

  Up to Day 29

• Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part A

  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); hemoglobin (high: \>180 g/L), lymphocytes (low: \<0.8x10\^9 cells per liter \[cells/L\]); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  Up to Day 40

• Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part B

  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); hemoglobin (high: \>180 g/L), lymphocytes (low: \<0.8x10\^9 cells/L); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  Up to Day 34

• Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part C

  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); hemoglobin (high: \>180 g/L), lymphocytes (low: \<0.8x10\^9 cells/L); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). The number of participants with any hematology abnormality of potential clinical importance is reported.

  Up to Day 29

• Number of Participants With Abnormal Urinalysis Dipstick Results-Part A

  Urine samples were taken for the assessment of following urine parameters: glucose, ketones, occult blood (OB) and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3

• Number of Participants With Urinalysis Dipstick Results for Potential of Hydrogen (pH)-Part A

  Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3

• Number of Participants With Abnormal Urinalysis Dipstick Results-Part B

  Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17

• Number of Participants With Urinalysis Dipstick Results (pH)-Part B

  Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17

• Number of Participants With Abnormal Urinalysis Dipstick Results-Part C

  Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.

  8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2

• Number of Participants With Urinalysis Dipstick Results (pH)-Part C

  Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.

  8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2

• Number of Participants With Vital Signs of Potential Clinical Importance-Part A

  Vital signs were measured in a supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 millimeters of mercury \[mmHg\] and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 beats per minute \[bpm\] and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  Up to Day 40

• Number of Participants With Vital Signs of Potential Clinical Importance-Part B

  Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 mmHg and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 bpm and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  Up to Day 34

• Number of Participants With Vital Signs of Potential Clinical Importance-Part C

  Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 mmHg and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 bpm and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.

  Up to Day 29

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A

  Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS 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. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Up to Day 40

• Number of Participants With Abnormal ECG Findings-Part B

  Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS 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. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Up to Day 34

• Number of Participants With Abnormal ECG Findings-Part C

  Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS 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. Data for worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Up to Day 29

• Area Under Tha Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

• AUC(0 to t) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

• AUC(0 to Inf) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Maximum Observed Plasma Concentration (Cmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

• Cmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Time to Maximum Observed Plasma Concentration (Tmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

• Tmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• Apparent Terminal Half-life (T1/2) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose

• T1/2 of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

• T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)

  Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

  Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)

Secondary Outcomes (20)

• AUC(0 to t) of GSK3439171A (Food Effect)-Part C

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• AUC(0 to Inf) of GSK3439171A (Food Effect)-Part C

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• Cmax for GSK3439171A (Food Effect)-Part C

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• Tmax for GSK3439171A-Part C

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

• T1/2 for GSK3439171A-Part C

  pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose

Study Arms (13)

Part A: P1,PBO/GSK3439171A Dose 2/GSK3439171A Dose 3

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 milligram (mg) up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence placebo (PBO) followed by Dose 2 of GSK3439171A followed by Dose 3 of GSK3439171A in period 1 (P1). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P1, GSK3439171A Dose 1/ PBO/GSK3439171A Dose 3

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and PBO as per randomized sequence: Dose 1 of GSK3439171A followed by PBO followed by Dose 3 of GSK3439171A in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P1, GSK3439171A Dose 1/ GSK3439171A Dose 2/ PBO

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 1 of GSK3439171A followed by Dose 2 of GSK3439171A followed by PBO in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P2, PBO/GSK3439171A Dose 5/GSK3439171A Dose 6

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 5 of GSK3439171A followed by Dose 6 of GSK3439171A in period 2 (P2). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P2, GSK3439171A Dose 4/ PBO/GSK3439171A Dose 6

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by PBO followed by Dose 6 of GSK3439171A in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P2, GSK3439171A Dose 4/ GSK3439171A Dose 5/ PBO

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by Dose 5 of GSK3439171A followed by PBO in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P3, PBO/GSK3439171A Dose 8/GSK3439171A Dose 9

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 8 of GSK3439171A followed by Dose 9 of GSK3439171A in Period 3 (P3). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P3, GSK3439171A Dose 7/ PBO/GSK3439171A Dose 9

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by PBO followed by Dose 9 of GSK3439171A in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part A: P3, GSK3439171A Dose 7/ GSK3439171A Dose 8/ PBO

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by Dose 8 of GSK3439171A followed by PBO in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part B: GSK3439171A

EXPERIMENTAL

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A in part B

Drug: GSK3439171A

Part B: Placebo

PLACEBO COMPARATOR

Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of Placebo in part B

Drug: Placebo

Part C: GSK3439171A fed followed by GSK3439171A fasted

EXPERIMENTAL

Subjects will administer GSK3439171A in Fed condition in Part C P1 followed by GSK3439171A in fasted condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Part C: GSK3439171A fasted followed by GSK3439171A fed

EXPERIMENTAL

Subjects will administer GSK3439171A in fasted condition in Part C P1 followed by GSK3439171A in fed condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.

Drug: GSK3439171A; Drug: Placebo

Interventions

GSK3439171A DRUG

Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P1, GSK3439171A Dose 1/ GSK3439171A Dose 2/ PBO; Part A: P1, GSK3439171A Dose 1/ PBO/GSK3439171A Dose 3; Part A: P1,PBO/GSK3439171A Dose 2/GSK3439171A Dose 3; Part A: P2, GSK3439171A Dose 4/ GSK3439171A Dose 5/ PBO; Part A: P2, GSK3439171A Dose 4/ PBO/GSK3439171A Dose 6; Part A: P2, PBO/GSK3439171A Dose 5/GSK3439171A Dose 6; Part A: P3, GSK3439171A Dose 7/ GSK3439171A Dose 8/ PBO; Part A: P3, GSK3439171A Dose 7/ PBO/GSK3439171A Dose 9; Part A: P3, PBO/GSK3439171A Dose 8/GSK3439171A Dose 9; Part B: GSK3439171A; Part C: GSK3439171A fasted followed by GSK3439171A fed; Part C: GSK3439171A fed followed by GSK3439171A fasted

Placebo DRUG

Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Part A: P1, GSK3439171A Dose 1/ GSK3439171A Dose 2/ PBO; Part A: P1, GSK3439171A Dose 1/ PBO/GSK3439171A Dose 3; Part A: P1,PBO/GSK3439171A Dose 2/GSK3439171A Dose 3; Part A: P2, GSK3439171A Dose 4/ GSK3439171A Dose 5/ PBO; Part A: P2, GSK3439171A Dose 4/ PBO/GSK3439171A Dose 6; Part A: P2, PBO/GSK3439171A Dose 5/GSK3439171A Dose 6; Part A: P3, GSK3439171A Dose 7/ GSK3439171A Dose 8/ PBO; Part A: P3, GSK3439171A Dose 7/ PBO/GSK3439171A Dose 9; Part A: P3, PBO/GSK3439171A Dose 8/GSK3439171A Dose 9; Part B: Placebo; Part C: GSK3439171A fasted followed by GSK3439171A fed; Part C: GSK3439171A fed followed by GSK3439171A fasted

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Only males are eligible for this study
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Subjects with Body weight \>=50.0 kilograms (Kg) (110 lbs.) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per square meter (inclusive).
• Only male subjects are eligible for this study. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male subjects are eligible to participate if they agree to the following during the their entire enrolment in the study plus an additional 5 days or 5 terminal half-lives (whichever is longer): Refrain from donating sperm plus either be abstinent from sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier (female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year)
• Subjects must be capable of giving signed informed consent
• Subjects are excluded from the study if they have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Subjects are excluded from the study if they have any clinically significant abnormal vital signs
• Subjects are excluded from the study if they have Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
• Subjects are excluded from the study if they have ALT \>1.5 times upper limit of normal (ULN)
• Subjects are excluded from the study if Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• Subjects are excluded from the study if they have current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects are excluded from the study if they have QTc \>450 milliseconds
• Subjects who are unable to refrain from the use of prescription or non-prescription drugs, including aspirin, Non-steroidal Anti-inflammatory Drugs (NSAIDs), vitamins, herbal and dietary supplements (including St John's Wort) within 10 days prior to the first dose of study medication.
• In cases, where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days
• Subjects with exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Subjects with current enrolment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Muscular Dystrophies

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A is a Crossover group single ascending dose study with 2 arms per cohort that is subject and investigator blinded. Part B is a Parallel group repeat dose study with 2 arms per cohort that is subject and investigator blinded. Part C is a Crossover group food effect study with 2 arms per cohort that is not-masked."

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 13, 2018
• Study Start: August 30, 2018
• Primary Completion: August 26, 2019
• Study Completion: August 26, 2019
• Last Updated: July 10, 2020
• Results First Posted: July 10, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)