| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04604795 | Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Interaction Between GSK3915393 and Grapefruit Juice and Itraconazole | PHASE1 | COMPLETED | 65 | — | — | Nov 4, 2020 | Jun 29, 2021 | May 9, 2023 | 1 | United Kingdom |
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. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
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. Number of participants with treatment related AEs were presented.
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. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
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. Number of participants with treatment related AEs are presented.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase \[ALT\]), \>=2\*ULN (U/L) (Aspartate Aminotransferase (\[AST\]), \>=2\*ULN (Alkaline Phosphatase \[ALP\]) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \> 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as within (w/in) range.
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to (within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Blood samples were collected for analysis of hematology parameters. PCI ranges were \>1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury\[mmHg\]): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \>=2\*ULN (U/L)(ALT), \>=2\*ULN (U/L) (AST), \>=2\*ULN (ALP) (U/L), \>=1.5\*ULN (micromoles per liter) (bilirubin), \<2 or \>2.75 millimoles/liter (L) (mmol/L)(calcium), \<3 or \>11 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), \<130 or \>150 mmol/L (sodium),\<50 or \>85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within \[w/in\] range or no change \[NC\], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High \>10.5 mmol/L. Participants were counted in worst case category that their value changes to (within \[w/in\] range or NC, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline \> 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1\*10\^9 cell per liter (cells/L) (eosinophils), \<0.2 or \>0.54 proportion of red blood cells in blood (hematocrit), \<80 or \>180 grams per liter(g/L) (hemoglobin), \<3 or \>20 x10\^9 cells/L (leukocytes), \<0.8\*10\^9 cells/L (lymphocytes), \<1.5 or \>16\*10\^9 cells/L (neutrophils) and \<100 or \>550\*10\^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example \[e.g.\], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute):\<=8 (low) or \>20 (high) and body temperature (degrees Celsius) \<=35.5 (low) or \>38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Cmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Tmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. AUC(0-inf) was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. t1/2 was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
| Arm | Type | Description |
|---|---|---|
| Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A) | EXPERIMENTAL | In Part A, participants will receive dose levels (DLs) 1, 3, 4, IV microdose of GSK3915393, and placebo in a pre-determined sequence (Sequence A). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. |
| Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B) | EXPERIMENTAL | In Part A, participants will receive dose levels 1, 2, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence B). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. |
| Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C) | EXPERIMENTAL | In Part A, participants will receive dose levels 1, 2, 3, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence C). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. |
| Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D) | EXPERIMENTAL | In Part A, participants will receive dose levels 2, 3, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence D). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. |
| Part B: Cohort 1: Participants receiving GSK3915393 DL X | EXPERIMENTAL | Participants will receive GSK3915393 dose level X twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A. |
| Part B: Cohort 1: Participants receiving placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching GSK3915393 dose level X during Part B of the study. |
| Part B: Cohort 2: Participants receiving GSK3915393 DL Y | EXPERIMENTAL | Participants will receive GSK3915393 dose level Y twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B. |
| Part B: Cohort 2: Participants receiving placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching GSK3915393 dose level Y twice daily during Part B of the study |
| Part B: Cohort 3: Participants receiving GSK3915393 DL Z | EXPERIMENTAL | Participants will receive GSK3915393 dose level Z twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B. |
| Part B: Cohort 3: Participants receiving placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching GSK3915393 dose level Z twice daily during Part B of the study. |
| Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A) | EXPERIMENTAL | Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and itraconazole (ITZ) in period 2. Participants will then receive oral GSK3915393 plus water in period 3, oral GSK3915393 plus grape fruit juice (GFJ) in period 4 and oral GSK3915393 plus ITZ in period 5. |
| Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B) | EXPERIMENTAL | Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and ITZ in period 2. Participants will then receive oral GSK3915393 plus GFJ in period 3, oral GSK3915393 plus water in period 4 and oral GSK3915393 plus ITZ in period 5. |
| Name | Type | Description |
|---|---|---|
| GSK3915393 Capsules | DRUG | GSK3915393 capsules will be given orally. |
| GSK3915393 Solution for Infusion | DRUG | GSK3915393 solution for infusion will be administered intravenously. |
| Placebo capsules | DRUG | Placebo matching GSK3915393 capsules will be given orally. |
| Itraconazole | DRUG | Participants will be administered with GSK3915393 along with ITZ orally |
| Water | OTHER | Participants will be administered with GSK3915393 along with water orally |
| Grape fruit juice | OTHER | Participants will be administered with GSK3915393 along with GFJ orally |
Inclusion Criteria: * Between 18 and 50 years of age inclusive, at the time of signing the informed consent. * Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Negative coron...
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