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Nemiralisib is a potent anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD) and other inflammatory lung diseases. The Cytochrome P450 3A4 (CYP3A4) is a major route of clearance for nemiralisib. The co-administration of drug therapies, which modulate CYP3A4, may alter the exposure of nemiralisib. Hence, this clinical drug interaction study with itraconazole (a potent CYP3A4 inhibitor) is required. The study will evaluate the PK, safety and tolerability of nemiralisib when administered alone and when administered concomitantly with repeat doses of itraconazole in healthy males and females. Subjects will receive treatment with nemiralisib alone in Period 1 and itraconazole followed by nemiralisib in Period 2 in single sequence crossover manner. Approximately 20 subjects will be enrolled such that approximately 16 evaluable subjects complete the study. Each subject will participate in the study for approximately 7 weeks including screening visit, 2 treatment periods and a follow up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects receiving nemiralisib and itraconazole | Experimental | Eligible subjects will receive a single dose of 100 micrograms (mcg) nemiralisib on Day 1 in Period 1. Subjects will also receive a single dose of 200 milligrams (mg) itraconazole in the morning from Day 1 to Day 10 and single dose of 100 mcg nemiralisib on Day 5, one hour after the dose of itraconazole in Period 2. There will be a washout of at least 14 days between the administration of nemiralisib in Period 1 and Period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nemiralisib | Drug | Nemiralisib will be given as 100 mcg via ELLIPTA Dry Powder Inhaler with 30 doses per inhaler/ 100 mcg total dose. ELLIPTA® is a registered trademark of GlaxoSmithKline group of companies. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic parameters of nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic population comprised of all participants enrolled in the study who took at least 1 dose of nemiralisib and for whom a nemiralisib pharmacokinetic sample was obtained and analyzed. | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
| Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
| Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma |
| Measure | Description | Time Frame |
|---|---|---|
| AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32009006 | Background | Patel A, Wilson R, Harrell AW, Taskar KS, Taylor M, Tracey H, Riddell K, Georgiou A, Cahn AP, Marotti M, Hessel EM. Drug Interactions for Low-Dose Inhaled Nemiralisib: A Case Study Integrating Modeling, In Vitro, and Clinical Investigations. Drug Metab Dispos. 2020 Apr;48(4):307-316. doi: 10.1124/dmd.119.089003. Epub 2020 Feb 2. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
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.
A total of 20 participants were enrolled at a single center in the United States.
This was a Phase I, single center, open label, one sequence cross-over study conducted in healthy males and females of non-child bearing potential to evaluate the pharmacokinetic (PK), safety and tolerability of nemiralisib administered alone and concomitantly with repeated doses of itraconazole.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nemiralisib 100 mcg | Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days. |
| FG001 | Itraconazole 200 Milligram(mg) With 100mcg Nemiralisib | After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Up to 6 Days) |
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| Washout Period (Up to 14 Days) |
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| Treatment Period 2 (Up to 11 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants received a single 100 mcg inhaled oral dose of Nemiralisib on Day 1 in Period 1, followed by a washout period of 14 days. In treatment period 2, participants received an oral dose of 200 mg itraconazole from Days 1 to 10 and on Day 5 a single inhaled oral dose of 100 mcg nemiralisib was administered one hour after itraconazole dosing. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic parameters of nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic population comprised of all participants enrolled in the study who took at least 1 dose of nemiralisib and for whom a nemiralisib pharmacokinetic sample was obtained and analyzed. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picogram per milliliter | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
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Serious adverse events (SAEs) and adverse events (AEs) were collected up to Day 35
AEs and SAEs were collected in the Safety Population.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nemiralisib 100 mcg | Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 12, 2017 | Nov 20, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 12, 2018 | Nov 20, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C000629641 | Nemiralisib |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Subjects will receive nemiralisib alone on Day 1 in Period 1 and itraconazole from Day 1 to Day 10 followed by nemiralisib on Day 5 in Period 2.
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This will be an open-label study. Hence, there will be no masking.
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| Itraconazole | Drug | Itraconazole will be given as 100 mg per capsule per day administered orally with water |
|
Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. |
| Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
| Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma | Blood samples were collected at indicated time points after administration of repeated doses of itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
| AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
| Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
| T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
| Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A 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, associated with liver injury and impaired liver function or any other situations as per Medical or scientific judgement. Safety population comprised of all participants enrolled in the study, who took at least one dose of study treatment. | Up to 35 days |
| Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium and sodium. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 6 |
| Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg When Co-administered With Itraconazole 200 mg Repeated Dose: Calcium, Glucose, Potassium and Sodium | Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium and sodium. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1), Day 2, 4, 6, 8 and 10 |
| Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Alkaline Phosphate, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphate, ALT and AST at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg When Co-administered With Itraconazole 200 mg Repeated Dose: Alkaline Phosphate, ALT and AST | Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphate, ALT and AST at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline, Day 2, 4, 6, 8 and 10 |
| Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, direct bilirubin and creatinine at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, direct bilirubin and creatinine at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline, Day 2, 4, 6, 8 and 10 |
| Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of total protein at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Blood samples were collected for the analysis of total protein at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline, Day 2, 4, 6, 8 and 10 |
| Change From Baseline in Hematology Parameters When Single Oral Dose of Nemiralisib 100 mcg Administered: Lymphocytes, Neutrophils, Platelets, Basophils, Eosinophils, Monocytes, Erythrocytes and White Blood Cells (WBC) | Blood samples were collected for the analysis of hematology parameters including lymphocytes, neutrophils, platelets, basophils, eosinophils, monocytes, erythrocytes and WBCs at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in Hematology Parameters When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Lymphocytes, Neutrophils, Platelets, Basophils, Eosinophils, Monocytes, Erythrocytes and WBC | Blood samples were collected for the analysis of hematology parameters including lymphocytes, neutrophils, platelets, basophils, eosinophils, monocytes, erythrocytes and WBCs at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of hematocrit at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of hematocrit at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of hemoglobin at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of hemoglobin at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of MCH at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of MCH at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of MCV at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of MCV at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of reticulocyte percentage at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 6 |
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of reticulocyte percentage at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline and Day 10 |
| Specific Gravity at Indicated Time Points | Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is the measure of the concentration solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. | Days -1, 6 and 10 |
| Number of Participants With Abnormal Urinalysis Parameter | The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as Trace and 2+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented. | Days -1, 6 and 10 |
| Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). | Day -1, 6 and 10 |
| Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | A microscopic examination was performed as part of a routine urinalysis. The microscopic exam was performed on urine sediment - urine was centrifuged to concentrate the substances in it at the bottom of a tube. The fluid at the top of the tube was then discarded and the drops of fluid remaining were examined under a microscope. Cells, crystals, and other substances were counted and reported either as the number observed "per low power field" (LPF) or "per high power field" (HPF). | Day -1 |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Full 12-lead ECGs were recorded with the participant in a supine position. The number of participants with abnormal clinically significant ECG findings for worst case post-Baseline is presented. | Period 1: Up to Day 6; Period 2: Up to Day 10 |
| Number of Participants With Abnormal Spirometry Values | Spirometry assessments were planned but not performed. | Period 1: Day -1; Period 2: Day 4 |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Day 6 |
| Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 |
| Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Day 6 |
| Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 |
| Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Respiratory rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Day 6 |
| Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Respiratory rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 |
| Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose) and Day 6 |
| Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Count of Participants |
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| OG000 |
| Nemiralisib 100 mcg |
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days. |
| OG001 | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole. |
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| Primary | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram per milliliter | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per milliliter | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
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| Primary | Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma | Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
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| Primary | Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma | Blood samples were collected at indicated time points after administration of repeated doses of itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Median | Full Range | Hour | Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5 |
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| Secondary | AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed. NA indicates AUC (0-inf) for hydroxy itraconazole (Day 1 and Day 5) and Itraconazole (Day 5) could not be calculated as it was not possible to get accurate measurements since the length was too long for sampling. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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| Secondary | AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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| Secondary | Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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| Secondary | T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. Only those participants with data available at specified time points were analyzed. NA indicates T1/2 for hydroxy itraconazole (Day 1 and Day 5) and Itraconazole (Day 5) could not be calculated as it was not possible to get accurate measurements since the length was too long for sampling. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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| Secondary | Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Blood samples were collected at indicated time points after administration of repeated doses of Itraconazole and Hydroxy Itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pharmacokinetic population. | Posted | Median | Full Range | Hour | Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5 |
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| Secondary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A 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, associated with liver injury and impaired liver function or any other situations as per Medical or scientific judgement. Safety population comprised of all participants enrolled in the study, who took at least one dose of study treatment. | Safety population. | Posted | Count of Participants | Participants | Up to 35 days |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium and sodium. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Millimoles/Liter | Baseline (Day -1) and Day 6 |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg When Co-administered With Itraconazole 200 mg Repeated Dose: Calcium, Glucose, Potassium and Sodium | Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium and sodium. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Millimoles/Liter | Baseline (Day -1), Day 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Alkaline Phosphate, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphate, ALT and AST at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | International Units/ Liter | Baseline and Day 6 |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg When Co-administered With Itraconazole 200 mg Repeated Dose: Alkaline Phosphate, ALT and AST | Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphate, ALT and AST at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | International Units/ Liter | Baseline, Day 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, direct bilirubin and creatinine at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline and Day 6 |
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| Secondary | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, direct bilirubin and creatinine at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline, Day 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of total protein at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Gram per liter | Baseline and Day 6 |
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| Secondary | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Blood samples were collected for the analysis of total protein at indicated time points. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Gram per liter | Baseline, Day 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline in Hematology Parameters When Single Oral Dose of Nemiralisib 100 mcg Administered: Lymphocytes, Neutrophils, Platelets, Basophils, Eosinophils, Monocytes, Erythrocytes and White Blood Cells (WBC) | Blood samples were collected for the analysis of hematology parameters including lymphocytes, neutrophils, platelets, basophils, eosinophils, monocytes, erythrocytes and WBCs at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline and Day 6 |
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| Secondary | Change From Baseline in Hematology Parameters When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Lymphocytes, Neutrophils, Platelets, Basophils, Eosinophils, Monocytes, Erythrocytes and WBC | Blood samples were collected for the analysis of hematology parameters including lymphocytes, neutrophils, platelets, basophils, eosinophils, monocytes, erythrocytes and WBCs at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline and Day 10 |
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| Secondary | Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of hematocrit at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Percentage of red blood cells in blood | Baseline and Day 6 |
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| Secondary | Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of hematocrit at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Percentage of red blood cells in blood | Baseline and Day 10 |
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| Secondary | Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of hemoglobin at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline and Day 6 |
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| Secondary | Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of hemoglobin at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline and Day 10 |
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| Secondary | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of MCH at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Picograms per liter | Baseline and Day 6 |
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| Secondary | Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of MCH at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Picograms per liter | Baseline and Day 10 |
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| Secondary | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of MCV at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Femtoliter | Baseline and Day 6 |
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| Secondary | Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of MCV at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Femtoliter | Baseline and Day 10 |
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| Secondary | Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered | Blood samples were collected for the analysis of reticulocyte percentage at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Percentage | Baseline and Day 6 |
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| Secondary | Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Blood samples were collected for the analysis of reticulocyte percentage at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Percentage | Baseline and Day 10 |
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| Secondary | Specific Gravity at Indicated Time Points | Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is the measure of the concentration solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. | Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Mean | Standard Deviation | Grams per cubic centimeter | Days -1, 6 and 10 |
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| Secondary | Number of Participants With Abnormal Urinalysis Parameter | The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as Trace and 2+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented. | Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Count of Participants | Participants | Days -1, 6 and 10 |
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| Secondary | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). | Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Count of Participants | Participants | Day -1, 6 and 10 |
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| Secondary | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | A microscopic examination was performed as part of a routine urinalysis. The microscopic exam was performed on urine sediment - urine was centrifuged to concentrate the substances in it at the bottom of a tube. The fluid at the top of the tube was then discarded and the drops of fluid remaining were examined under a microscope. Cells, crystals, and other substances were counted and reported either as the number observed "per low power field" (LPF) or "per high power field" (HPF). | Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). | Posted | Count of Participants | Participants | Day -1 |
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| Secondary | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Full 12-lead ECGs were recorded with the participant in a supine position. The number of participants with abnormal clinically significant ECG findings for worst case post-Baseline is presented. | Safety population. | Posted | Count of Participants | Participants | Period 1: Up to Day 6; Period 2: Up to Day 10 |
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| Secondary | Number of Participants With Abnormal Spirometry Values | Spirometry assessments were planned but not performed. | Safety population. | Posted | Period 1: Day -1; Period 2: Day 4 |
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| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Millimeter of mercury | Baseline (Day 1, pre-dose) and Day 6 |
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| Secondary | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Millimeter of mercury | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1, pre-dose) and Day 6 |
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| Secondary | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Respiratory rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1, pre-dose) and Day 6 |
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| Secondary | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Respiratory rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 |
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| Secondary | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Celsius | Baseline (Day 1, pre-dose) and Day 6 |
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| Secondary | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Safety population. | Posted | Mean | Standard Deviation | Celsius | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 |
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| 0 |
| 20 |
| 0 |
| 20 |
| 1 |
| 20 |
| EG001 | Nemiralisib 100 mcg With Itraconazole 200 mg | After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole. | 0 | 20 | 0 | 20 | 4 | 20 |
| Hypoacusis | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010879 |
| Piperazines |
| Day 5; n=0, 20 |
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| Day 5; n=0, 20 |
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| Day 5, n=0, 14 |
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| Day 5; n=0, 20 |
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| Hydroxy Itraconazole, Day 1 |
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| Hydroxy Itraconazole, Day 5 |
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| Title | Measurements |
|---|---|
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| Hydroxy Itraconazole, Day 5 |
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| Title | Measurements |
|---|---|
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| Hydroxy Itraconazole, Day 5 |
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| Hydroxy Itraconazole, Day 1 |
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| Hydroxy Itraconazole, Day 5 |
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| Hydroxy Itraconazole, Day 5 |
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| Title | Measurements |
|---|---|
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| Sodium |
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| Title | Measurements |
|---|---|
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| Glucose, Day 8 |
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| Glucose, Day 10 |
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| Calcium, Day 2 |
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| Calcium, Day 4 |
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| Calcium, Day 6 |
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| Calcium, Day 8 |
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| Calcium, Day 10 |
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| Potassium, Day 2 |
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| Potassium, Day 4 |
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| Potassium, Day 6 |
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| Potassium, Day 8 |
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| Potassium, Day 10 |
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| Sodium, Day 2 |
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| Sodium, Day 4 |
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| Sodium, Day 6 |
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| Sodium, Day 8 |
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| Sodium, Day 10 |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Alkaline phosphate, Day 8 |
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| Alkaline phosphate, Day 10 |
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| ALT, Day 2 |
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| ALT, Day 4 |
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| ALT, Day 6 |
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| ALT, Day 8 |
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| ALT, Day 10 |
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| AST, Day 2 |
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| AST, Day 4 |
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| AST, Day 6 |
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| AST, Day 8 |
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| AST, Day 10 |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Bilirubin, Day 8 |
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| Bilirubin, Day 10 |
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| Direct bilirubin, Day 2 |
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| Direct bilirubin, Day 4 |
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| Direct bilirubin, Day 6 |
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| Direct bilirubin, Day 8 |
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| Direct bilirubin, Day 10 |
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| Creatinine, Day 2 |
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| Creatinine, Day 4 |
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| Creatinine, Day 6 |
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| Creatinine, Day 8 |
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| Creatinine, Day 10 |
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| Title | Measurements |
|---|---|
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| Day 8 |
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| Day 10 |
|
| Title | Measurements |
|---|---|
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| Basophils |
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| Eosinophils |
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| Monocytes |
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| Erythrocytes |
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| WBC |
|
| Title | Measurements |
|---|---|
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| Basophils |
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| Eosinophils |
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| Monocytes |
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| Erythrocytes |
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| WBC |
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| Day 6, n=20, 0 |
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| Day 10, n=0, 20 |
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| Protein, Day -1, Trace, n=20,19 |
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| Erythrocytes, Day-1,Trace, n=20,19 |
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| Erythrocytes, Day-1,2+, n=20,19 |
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| Leukocytes, Day 6, Trace, n=20,0 |
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| Leukocytes, Day 6, 2+, n=20,0 |
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| Day -1, pH=6, n=20,19 |
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| Day -1, pH=7, n=20,19 |
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| Day -1, pH=8, n=20,19 |
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| Day 6, pH=5, n=20,0 |
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| Day 6, pH=6, n=20,0 |
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| Day 6, pH=7, n=20,0 |
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| Day 10, pH=5, n=0,20 |
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| Day 10, pH=6, n=0,20 |
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| Day 10, pH=7, n=0,20 |
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| Cast2, n=2,2 |
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| Cast3, n=2,2 |
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| Cast10, n=2,2 |
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| Epithelial cells 0, n=2,2 |
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| Epithelial cells 1, n=2,2 |
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| Erythrocytes 1, n=2,2 |
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| Erythrocytes 3, n=2,2 |
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| Erythrocytes 7, n=2,2 |
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| Erythrocytes 9, n=2,2 |
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| Leukocytes 1, n=2,2 |
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| Leukocytes 2, n=2,2 |
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| Title | Measurements |
|---|---|
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| SBP, Day 8 |
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| SBP, Day 10 |
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| DBP, Day 2 |
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| DBP, Day 4 |
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| DBP, Day 6 |
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| DBP, Day 8 |
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| DBP, Day 10 |
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| Title | Measurements |
|---|---|
|
| Day 8 |
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| Day 10 |
|
| Title | Measurements |
|---|---|
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| Day 8 |
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| Day 10 |
|
| Title | Measurements |
|---|---|
|
| Day 8 |
|
| Day 10 |
|