A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical Trial to Assess the Relative Bioavailability of a Tablet Compared to a Capsule of GSK3640254 and to Assess the Effect of Food on the GSK3640254 Tablet in Healthy Participants
Overview
- Phase
- Phase 1
- Intervention
- GSK3640254 Tablet
- Conditions
- HIV Infections
- Sponsor
- ViiV Healthcare
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1: Treatment AB
Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Tablet
Part 1: Treatment AB
Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Capsule
Part 1: Treatment BA
Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Tablet
Part 1: Treatment BA
Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Capsule
Part 2: Treatment CDE
Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Tablet
Part 2: Treatment DEC
Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Tablet
Part 2: Treatment ECD
Participants will receive a single dose of GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.
Intervention: GSK3640254 Tablet
Outcomes
Primary Outcomes
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Maximum Observed Concentration (Cmax) for GSK3640254-Part 1
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 1
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to Inf) for GSK3640254-Part 2
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to t) for GSK3640254-Part 2
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 2
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Cmax for GSK3640254-Part 2
Time Frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Secondary Outcomes
- Number of Participants With AEs and SAEs-Part 2(Up to Day 19)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1(Up to Day 12)
- Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocytes Count-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Hemoglobin-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Hematocrit-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocytes Count-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Hemoglobin-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Hematocrit-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocytes Count-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hemoglobin-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hematocrit-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocytes Count-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hemoglobin-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Hematocrit-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, Blood Urea Nitrogen (BUN), Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: Specific Gravity-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: Urobilinogen-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: Potential of Hydrogen (pH)-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: Specific Gravity-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: Urobilinogen-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Absolute Values for Urine Parameter: pH-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: Specific Gravity-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: Urobilinogen-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: pH-Part 1(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: Specific Gravity-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: Urobilinogen-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Change From Baseline in Urine Parameter: pH-Part 2(Baseline (Day -1), Day 2 and Day 5)
- Number of Participants With Abnormal Urine Dipstick Results-Part 1(Day 2 and Day 5)
- Number of Participants With Abnormal Urine Dipstick Results-Part 2(Day 2 and Day 5)
- Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)-Part 1(Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5)
- Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2(Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5)
- Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 1(Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5)
- Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2(Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5)
- Absolute Values for Vital Sign: Pulse Rate-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Sign: Temperature-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Sign: Temperature-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Signs: SBP and DBP-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Sign: Pulse Rate-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Sign: Respiratory Rate-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Sign: Temperature-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Sign: Respiratory Rate-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Signs: SBP and DBP-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Signs: DBP and SBP-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Absolute Values for Vital Sign: Pulse Rate-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Sign: Pulse Rate-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Sign: Respiratory Rate-Part 1(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Change From Baseline in Vital Sign: Respiratory Rate-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Plasma Concentration of GSK3640254-Part 1(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Change From Baseline in Vital Sign: Temperature-Part 2(Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5)
- Lag Time for Absorption (Tlag) for GSK3640254-Part 1(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Volume of Distribution (Vz/F) for GSK3640254-Part 1(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Terminal Phase Half-life (t1/2) for GSK3640254-Part 1(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Apparent Oral Clearance (CL/F) for GSK3640254-Part 1(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Tlag for GSK3640254-Part 2(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- T1/2 for GSK3640254-Part 2(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- CL/F for GSK3640254-Part 2(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Vz/F for GSK3640254-Part 2(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)
- Plasma Concentration of GSK3640254-Part 2(pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose)