Trial Outcomes & Findings for A Study to Compare the Relative Bioavailability of Two Different Formulations of GSK3640254 (NCT NCT03575962)

Last Updated: 2019-09-06

Results Overview

Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and percentage (%) geometric coefficient of variation have been presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post-dose in each treatment period

Results posted on

2019-09-06

Participant Flow

This was a single center, open-label, randomized, two-period crossover study to assess the relative bioavailability of a mesylate salt capsule of GSK3640254 compared to a hydrochloride salt capsule in healthy participants.

Participants received treatment in one of the two sequences; regimen A (GSK3640254 hydrochloride salt capsule) followed by regimen B (GSK3640254 mesylate salt capsule) or vice versa in each of the treatment period 1 and 2. A total of 14 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	GSK3640254 200 Mg-hydrochloride Salt Followed by Mesylate Salt Eligible participants received a single dose of GSK3640254 200 milligram (mg) bis-hydrochloride salt (100 mg x 2 capsules) administered orally on Day 1 in treatment period 1 after a moderate fat meal. It was followed by a washout period of minimum 7 days. Participants received GSK3640254 200 mg mesylate salt (100 mg x 2 capsules) administered orally on Day 1 in treatment period 2 after a moderate fat meal.	GSK3640254 200 Mg-mesylate Salt Followed by Hydrochloride Salt Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2 capsules) administered orally on Day 1 in treatment period 1 after a moderate fat meal. It was followed by a washout period of minimum 7 days. Participants received GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2 capsules) administered orally on Day 1 in treatment period 2 after a moderate fat meal.
Treatment Period 1 (4 Days) STARTED	7	7
Treatment Period 1 (4 Days) COMPLETED	7	7
Treatment Period 1 (4 Days) NOT COMPLETED	0	0
Washout Period (7 Days) STARTED	7	7
Washout Period (7 Days) COMPLETED	7	7
Washout Period (7 Days) NOT COMPLETED	0	0
Treatment Period 2 (4 Days) STARTED	7	7
Treatment Period 2 (4 Days) COMPLETED	7	7
Treatment Period 2 (4 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Compare the Relative Bioavailability of Two Different Formulations of GSK3640254

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2 capsules) followed by GSK3640254 200 mg mesylate salt (100 mg x 2 capsules) or vice versa, administered orally on Day 1 in each treatment period 1 and 2 following a moderate fat meal. The washout period was of minimum 7 days between the treatment periods.
Age, Continuous	33.9 Years STANDARD_DEVIATION 12.09 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post-dose in each treatment period

Population: PK Population comprising of participants in the Safety Population for whom at least one PK sample was obtained, analyzed and evaluable drug concentrations reported. Only those participants with data available at the specified data points were analyzed.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3640254 Following Single Oral Dose in Healthy Participants	23.5666 Hour*microgram per milliliter Geometric Coefficient of Variation 27.2	27.6204 Hour*microgram per milliliter Geometric Coefficient of Variation 46.7

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period

Population: PK Population

Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of relative bioavailability (Frel). Point estimate and 90% confidence interval (CI) for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for AUC(0-t).

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Area Under the Concentration-time Curve From Zero to Time of Last Sample Taken (AUC[0-t]) of GSK3640254 Following Single Oral Dose in Healthy Participants	20.2797 Hour*microgram per milliliter Geometric Coefficient of Variation 32.9	22.6494 Hour*microgram per milliliter Geometric Coefficient of Variation 40.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period

Population: PK Population

Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of Frel. Point estimate and 90% CI for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for Cmax.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Maximum Observed Concentration (Cmax) of GSK3640254 Following Single Oral Dose in Healthy Participants	0.7357 Microgram per milliliter Geometric Coefficient of Variation 35.7	0.8502 Microgram per milliliter Geometric Coefficient of Variation 40.5

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period

Population: PK Population

Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Time to Reach Maximum Observed Concentration (Tmax) of GSK3640254 Following Single Oral Dose in Healthy Participants	5.0 Hours Interval 2.0 to 6.0	5.0 Hours Interval 2.0 to 6.0

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose in each treatment period

Population: PK Population

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Concentration at 24 Hours Post-dose (C24h) of GSK3640254 Following Single Oral Dose in Healthy Participants	0.3439 Microgram per milliliter Geometric Coefficient of Variation 37.9	0.3855 Microgram per milliliter Geometric Coefficient of Variation 45.2

SECONDARY outcome

Timeframe: Up to 25 days

Population: Safety Population comprising of all randomized participants who received at least one dose of study treatment.

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, 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 and other situations according to medical or scientific judgement.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Any non-SAEs	4 Participants	6 Participants
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 3

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Blood samples were collected to analyze the clinical chemistry parameters; ALT, ALP and AST. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) ALT, Day 3, n=14,14	-1.9 International units per liter Standard Deviation 4.51	2.3 International units per liter Standard Deviation 6.84
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) ALP, Day 3, n=14,14	-1.2 International units per liter Standard Deviation 7.27	3.0 International units per liter Standard Deviation 5.87
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) AST, Day 3, n=13,14	-3.5 International units per liter Standard Deviation 3.82	-2.9 International units per liter Standard Deviation 6.55

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 3

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Blood samples were collected to analyze the clinical chemistry parameters; Bicarbonate, Calcium, Chloride, Glucose (fasting), Potassium, Sodium and Urea. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Calcium, Day 3, n=14,14	-0.044 Millimoles per liter Standard Deviation 0.1019	0.033 Millimoles per liter Standard Deviation 0.0961
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Chloride, Day 3, n=14,14	-0.5 Millimoles per liter Standard Deviation 1.61	-1.7 Millimoles per liter Standard Deviation 1.94
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Potassium, Day 3, n=14,14	0.21 Millimoles per liter Standard Deviation 0.435	0.06 Millimoles per liter Standard Deviation 0.445
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Sodium, Day 3, n=14,14	-0.9 Millimoles per liter Standard Deviation 1.10	-1.1 Millimoles per liter Standard Deviation 1.56
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Urea, Day 3, n=14,14	-0.41 Millimoles per liter Standard Deviation 1.634	-0.39 Millimoles per liter Standard Deviation 0.849
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Bicarbonate, Day 3, n=14,14	-3.0 Millimoles per liter Standard Deviation 2.66	-2.6 Millimoles per liter Standard Deviation 2.31
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea Glucose (fasting), Day 3, n=12,14	-0.17 Millimoles per liter Standard Deviation 0.444	0.04 Millimoles per liter Standard Deviation 0.554

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 3

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Blood samples were collected to analyze the clinical chemistry parameters; Bilirubin, Creatinine and Direct Bilirubin. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin Bilirubin, Day 3, n=14,14	2.1 Micromoles per liter Standard Deviation 3.94	-0.3 Micromoles per liter Standard Deviation 3.81
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin Creatinine, Day 3, n=14,14	0.1 Micromoles per liter Standard Deviation 7.29	-0.1 Micromoles per liter Standard Deviation 5.74
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin Direct Bilirubin, Day 3, n=0,1	—	-1.0 Micromoles per liter Standard Deviation NA NA indicates that standard deviation could not be calculated for a single participant.

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 3

Population: Safety Population

Blood samples were collected to analyze the clinical chemistry parameter; Protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Change From Baseline in Clinical Chemistry Parameter; Protein	-0.5 Grams per liter Standard Deviation 3.72	1.4 Grams per liter Standard Deviation 4.03

SECONDARY outcome

Timeframe: Up to 22 days

Population: Safety Population

Blood samples were collected to analyze the hematology parameters; Hematocrit (Hct), Hemoglobin (Hb), Leukocytes, Lymphocytes, Neutrophils and Platelets. PCI ranges were Hct (Male and Female \[high: \>0.54 proportion of red blood cells in blood\]), Hb (Male and Female \[high: \>180 grams per liter\]), lymphocytes (low: \<0.8x10\^9 cells per liter), neutrophils (low: \<1.5x10\^9 cells per liter), platelets (low: \<100x10\^9 cells per liter and high: \>550x10\^9 cells per liter) and leukocytes (low: \<3x10\^9 cells per liter and high: \>12x10\^9 cells per liter). Participants were counted in the worst case category such that their value changed to (low, normal or high). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category.

Outcome measures

Outcome measures
Measure	GSK3640254 200 mg Hydrochloride Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg bis-hydrochloride salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.	GSK3640254 Capsule 200 mg Mesylate Salt n=14 Participants Eligible participants received a single dose of GSK3640254 200 mg mesylate salt (100 mg x 2) administered orally on Day 1 in either treatment period 1or 2 as per randomization.
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hct, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hct, To normal or no change	14 Participants	14 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hb, To high	1 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Leukocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Lymphocytes, To normal or no change	14 Participants	14 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Lymphocytes, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Neutrophils, To normal or no change	14 Participants	14 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Platelets, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hct, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hb, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Hb, To normal or no change	13 Participants	14 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Leukocytes, To normal or no change	14 Participants	13 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Leukocytes, To high	0 Participants	1 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Lymphocytes, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Neutrophils, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Neutrophils, To high	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Platelets, To low	0 Participants	0 Participants
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Platelets, To normal or no change	14 Participants	14 Participants

SECONDARY outcome

Timeframe: Day -1 and Day 3

Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine leukocyte esterase (LE), urine nitrite, urine occult blood, urine protein, urobilinogen and monitor urine potential of hydrogen (pH). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace and positive, indicating proportional concentrations in the urine sample. All the numeric result values \>0 have been considered as "positive".