A Phase 1 interventional study of Nemiralisib and Itraconazole in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-04-27.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
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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Exclusion Criteria:
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.
Drug: Nemiralisib · Drug: Itraconazole
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.
Itraconazole will be given as 100 mg per capsule per day administered orally with water
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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-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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10
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.
| Milestone | Nemiralisib 100 mcg | Itraconazole 200 Milligram(mg) With 100mcg Nemiralisib |
|---|---|---|
| Started | 20 | 0 |
| Completed | 20 | 0 |
| Not completed | 0 | 0 |
| Milestone | Nemiralisib 100 mcg | Itraconazole 200 Milligram(mg) With 100mcg Nemiralisib |
|---|---|---|
| Started | 20 | 0 |
| Completed | 20 | 0 |
| Not completed | 0 | 0 |
| Milestone | Nemiralisib 100 mcg | Itraconazole 200 Milligram(mg) With 100mcg Nemiralisib |
|---|---|---|
| Started | 0 | 20 |
| Completed | 0 | 20 |
| Not completed | 0 | 0 |
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.
| Hours*picogram per milliliter | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day 1, n=20, 0 | 3199.0 ± 29.8 | — |
| Day 5, n=0, 14 | — | 6272.7 ± 27.5 |
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.
| Hour*picogram per milliliter | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day 1; n=20, 0 | 2677.1 ± 30.2 | — |
| Day 5; n=0, 20 | — | 4802.3 ± 29.1 |
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.
| Picogram per milliliter | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day 1; n=20, 0 | 478.7 ± 41.9 | — |
| Day 5; n=0, 20 | — | 384.0 ± 34.0 |
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.
| Hours | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day 1, n=20, 0 | 40.03 ± 21.7 | — |
| Day 5, n=0, 14 | — | 64.00 ± 11.4 |
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.
| Hour | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day 1; n=20, 0 | 0.070 (0.07 to 0.08) | — |
| Day 5; n=0, 20 | — | 0.088 (0.08 to 0.10) |
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.
| Hour*nanogram per milliliter | Nemiralisib 100 mcg With Itraconazole 200 mg |
|---|---|
| Itraconazole, Day 1 | 1201.3 ± 46.3 |
| Itraconazole, Day 5 | NA ± NA |
| Hydroxy Itraconazole, Day 1 | NA ± NA |
| Hydroxy Itraconazole, Day 5 | NA ± NA |
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.
| Hour*nanogram per milliliter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Itraconazole, Day 1 | 891.7 ± 60.0 |
| Itraconazole, Day 5 | 4939.6 ± 60.2 |
| Hydroxy Itraconazole, Day 1 | 1862.6 ± 48.8 |
| Hydroxy Itraconazole, Day 5 | 10106.4 ± 50.3 |
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.
| Nanogram per milliliter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Itraconazole, Day 1 | 156.90 ± 59.0 |
| Itraconazole, Day 5 | 472.52 ± 63.7 |
| Hydroxy Itraconazole, Day 1 | 240.3 ± 45.2 |
| Hydroxy Itraconazole, Day 5 | 541.2 ± 41.8 |
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.
| Hour | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Itraconazole, Day 1 | 3.865 ± 7.7 |
| Itraconazole, Day 5 | NA ± NA |
| Hydroxy Itraconazole, Day 1 | NA ± NA |
| Hydroxy Itraconazole, Day 5 | NA ± NA |
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.
| Hour | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Itraconazole, Day 1 | 4.001 (2.00 to 6.00) |
| Itraconazole, Day 5 | 4.001 (2.00 to 6.00) |
| Hydroxy Itraconazole, Day 1 | 4.004 (3.00 to 6.01) |
| Hydroxy Itraconazole, Day 5 | 4.004 (3.00 to 8.01) |
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.
| Participants | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Any AE | 1 | 4 |
| Any SAE | 0 | 0 |
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.
| Millimoles/Liter | Nemiralisib 100 mcg |
|---|---|
| Glucose | -0.12 ± 0.247 |
| Calcium | 0.06 ± 0.070 |
| Potassium | 0.20 ± 0.290 |
| Sodium | -0.9 ± 2.05 |
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.
| Millimoles/Liter | Nemiralisib 100 mcg With Itraconazole 200 mg |
|---|---|
| Glucose, Day 2 | -0.08 ± 0.256 |
| Glucose, Day 4 | -0.12 ± 0.291 |
| Glucose, Day 6 | 1.22 ± 1.055 |
| Glucose, Day 8 | -0.22 ± 0.346 |
| Glucose, Day 10 | -0.22 ± 0.280 |
| Calcium, Day 2 | 0.02 ± 0.066 |
| Calcium, Day 4 | 0.03 ± 0.069 |
| Calcium, Day 6 | 0.05 ± 0.081 |
| Calcium, Day 8 | 0.00 ± 0.077 |
| Calcium, Day 10 | 0.03 ± 0.059 |
| Potassium, Day 2 | 0.07 ± 0.326 |
| Potassium, Day 4 | 0.29 ± 0.381 |
| Potassium, Day 6 | 0.01 ± 0.348 |
| Potassium, Day 8 | 0.21 ± 0.323 |
| Potassium, Day 10 | 0.20 ± 0.339 |
| Sodium, Day 2 | -1.0 ± 1.59 |
| Sodium, Day 4 | 0.0 ± 2.55 |
| Sodium, Day 6 | -1.6 ± 1.73 |
| Sodium, Day 8 | -1.0 ± 1.72 |
| Sodium, Day 10 | -1.6 ± 2.09 |
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.
| International Units/ Liter | Nemiralisib 100 mcg |
|---|---|
| Alkaline phosphate | 0.8 ± 8.08 |
| ALT | 1.5 ± 7.40 |
| AST | -0.5 ± 3.40 |
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.
| International Units/ Liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Alkaline phosphate, Day 2 | -7.0 ± 6.99 |
| Alkaline phosphate, Day 4 | -8.5 ± 7.00 |
| Alkaline phosphate, Day 6 | -7.2 ± 9.09 |
| Alkaline phosphate, Day 8 | -7.6 ± 8.02 |
| Alkaline phosphate, Day 10 | -5.3 ± 9.35 |
| ALT, Day 2 | -3.2 ± 4.46 |
| ALT, Day 4 | -3.2 ± 3.82 |
| ALT, Day 6 | -2.9 ± 3.11 |
| ALT, Day 8 | -2.6 ± 2.96 |
| ALT, Day 10 | -2.8 ± 4.79 |
| AST, Day 2 | -2.6 ± 3.82 |
| AST, Day 4 | -3.0 ± 3.18 |
| AST, Day 6 | -2.4 ± 2.96 |
| AST, Day 8 | -3.2 ± 2.91 |
| AST, Day 10 | -2.0 ± 3.87 |
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.
| Micromoles per liter | Nemiralisib 100 mcg |
|---|---|
| Bilirubin | 5.557 ± 7.2310 |
| Direct bilirubin | 2.394 ± 0.8595 |
| Creatinine | -3.094 ± 6.5872 |
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.
| Micromoles per liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Bilirubin, Day 2 | 0.428 ± 2.7670 |
| Bilirubin, Day 4 | 1.796 ± 2.5710 |
| Bilirubin, Day 6 | 2.907 ± 2.9928 |
| Bilirubin, Day 8 | 2.309 ± 2.6766 |
| Bilirubin, Day 10 | 3.506 ± 2.7447 |
| Direct bilirubin, Day 2 | 2.907 ± 0.9768 |
| Direct bilirubin, Day 4 | 2.394 ± 1.0230 |
| Direct bilirubin, Day 6 | 1.796 ± 0.8728 |
| Direct bilirubin, Day 8 | 2.052 ± 0.7018 |
| Direct bilirubin, Day 10 | 2.907 ± 1.3702 |
| Creatinine, Day 2 | 0.442 ± 8.8284 |
| Creatinine, Day 4 | 2.210 ± 7.5202 |
| Creatinine, Day 6 | 0.884 ± 7.5338 |
| Creatinine, Day 8 | 0.442 ± 7.8414 |
| Creatinine, Day 10 | 0.000 ± 8.6042 |
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.
| Gram per liter | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | 3.3 ± 3.85 |
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.
| Gram per liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Day 2 | -3.8 ± 3.52 |
| Day 4 | -3.4 ± 3.03 |
| Day 6 | 0.2 ± 3.74 |
| Day 8 | -2.4 ± 3.86 |
| Day 10 | -1.8 ± 2.95 |
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.
| 10^9 cells per liter | Nemiralisib 100 mcg |
|---|---|
| Lymphocytes | -0.264 ± 0.579 |
| Neutrophils | 0.198 ± 0.736 |
| Platelets | 8.4 ± 31.74 |
| Basophils | 0.003 ± 0.014 |
| Eosinophils | -0.038 ± 0.047 |
| Monocytes | -0.054 ± 0.108 |
| Erythrocytes | 242.0 ± 205.16 |
| WBC | -0.174 ± 0.981 |
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.
| 10^9 cells per liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Lymphocytes | -0.202 ± 0.339 |
| Neutrophils | -0.127 ± 0.659 |
| Platelets | -5.7 ± 28.24 |
| Basophils | -0.004 ± 0.012 |
| Eosinophils | 0.003 ± 0.057 |
| Monocytes | -0.014 ± 0.130 |
| Erythrocytes | 76.0 ± 165.83 |
| WBC | -0.366 ± 0.846 |
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.
| Percentage of red blood cells in blood | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered | 1.94 ± 2.067 |
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.
| Percentage of red blood cells in blood | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 0.14 ± 1.436 |
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.
| Grams per liter | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered | 7.3 ± 6.00 |
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.
| Grams per liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 1.9 ± 4.42 |
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.
| Picograms per liter | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.03 ± 0.459 |
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.
| Picograms per liter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | -0.12 ± 0.387 |
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.
| Femtoliter | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.47 ± 0.889 |
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.
| Femtoliter | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | -1.09 ± 0.972 |
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.
| Percentage | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.038 ± 0.302 |
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.
| Percentage | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 0.065 ± 0.267 |
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.
| Grams per cubic centimeter | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day -1, n=20, 19 | 1.0198 ± 0.00713 | 1.0207 ± 0.00863 |
| Day 6, n=20, 0 | 1.0188 ± 0.00614 | — |
| Day 10, n=0, 20 | — | 1.0175 ± 0.00583 |
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.
| Participants | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Ketones, Day -1, Trace, n=20,19 | 2 | 2 |
| Protein, Day -1, Trace, n=20,19 | 0 | 1 |
| Erythrocytes, Day-1,Trace, n=20,19 | 1 | 0 |
| Erythrocytes, Day-1,2+, n=20,19 | 1 | 1 |
| Leukocytes, Day 6, Trace, n=20,0 | 2 | — |
| Leukocytes, Day 6, 2+, n=20,0 | 1 | — |
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).
| Participants | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Day -1, pH=5, n=20,19 | 8 | 8 |
| Day -1, pH=6, n=20,19 | 9 | 8 |
| Day -1, pH=7, n=20,19 | 2 | 3 |
| Day -1, pH=8, n=20,19 | 1 | 0 |
| Day 6, pH=5, n=20,0 | 9 | — |
| Day 6, pH=6, n=20,0 | 8 | — |
| Day 6, pH=7, n=20,0 | 3 | — |
| Day 10, pH=5, n=0,20 | — | 9 |
| Day 10, pH=6, n=0,20 | — | 4 |
| Day 10, pH=7, n=0,20 | — | 7 |
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).
| Participants | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Cast0, n=2,2 | 1 | 0 |
| Cast2, n=2,2 | 0 | 1 |
| Cast3, n=2,2 | 1 | 0 |
| Cast10, n=2,2 | 0 | 1 |
| Epithelial cells 0, n=2,2 | 2 | 1 |
| Epithelial cells 1, n=2,2 | 0 | 1 |
| Erythrocytes 1, n=2,2 | 1 | 0 |
| Erythrocytes 3, n=2,2 | 0 | 1 |
| Erythrocytes 7, n=2,2 | 1 | 0 |
| Erythrocytes 9, n=2,2 | 0 | 1 |
| Leukocytes 1, n=2,2 | 2 | 1 |
| Leukocytes 2, n=2,2 | 0 | 1 |
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.
| Participants | Nemiralisib 100 mcg | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|---|
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 | 0 |
Spirometry assessments were planned but not performed.
No measurements were reported for this outcome.
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.
| Millimeter of mercury | Nemiralisib 100 mcg |
|---|---|
| SBP | -1.2 ± 4.21 |
| DBP | -0.5 ± 3.71 |
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.
| Millimeter of mercury | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| SBP, Day 2 | 0.2 ± 3.71 |
| SBP, Day 4 | -1.2 ± 6.37 |
| SBP, Day 6 | -2.6 ± 5.60 |
| SBP, Day 8 | -1.8 ± 6.15 |
| SBP, Day 10 | 1.4 ± 6.86 |
| DBP, Day 2 | -1.0 ± 3.04 |
| DBP, Day 4 | -0.7 ± 6.21 |
| DBP, Day 6 | -3.5 ± 4.16 |
| DBP, Day 8 | -3.4 ± 3.39 |
| DBP, Day 10 | -0.5 ± 3.52 |
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.
| Beats per minute | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | -1.9 ± 8.83 |
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.
| Beats per minute | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Day 2 | 1.9 ± 4.80 |
| Day 4 | 3.2 ± 6.44 |
| Day 6 | 1.4 ± 6.15 |
| Day 8 | 3.5 ± 7.83 |
| Day 10 | 2.3 ± 6.55 |
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.
| Breaths per minute | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | -0.4 ± 2.01 |
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.
| Breaths per minute | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Day 2 | -1.3 ± 1.87 |
| Day 4 | 0.3 ± 1.63 |
| Day 6 | -0.5 ± 1.82 |
| Day 8 | 0.1 ± 1.77 |
| Day 10 | -0.5 ± 2.24 |
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.
| Celsius | Nemiralisib 100 mcg |
|---|---|
| Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | 0.04 ± 0.188 |
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.
| Celsius | Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 |
|---|---|
| Day 2 | -0.03 ± 0.205 |
| Day 4 | -0.07 ± 0.239 |
| Day 6 | -0.03 ± 0.266 |
| Day 8 | -0.08 ± 0.234 |
| Day 10 | -0.07 ± 0.213 |
Collected over Serious adverse events (SAEs) and adverse events (AEs) were collected up to Day 35. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nemiralisib 100 mcg | 0/20 (0%) | 0/20 (0%) | 1/20 (5%) |
| Nemiralisib 100 mcg With Itraconazole 200 mg | 0/20 (0%) | 0/20 (0%) | 4/20 (20%) |
| Event | Nemiralisib 100 mcg | Nemiralisib 100 mcg With Itraconazole 200 mg |
|---|---|---|
| Viral upper respiratory tract infectionInfections and infestations | 0/20 | 2/20 |
| HypoacusisEar and labyrinth disorders | 0/20 | 1/20 |
| Dry eyeEye disorders | 0/20 | 1/20 |
| HeadacheNervous system disorders | 1/20 | 0/20 |
| Age, Continuous(Years) | All Study Participants |
|---|---|
| Mean | 36.1 ± 12.37 |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 0 |
| Male | 20 |
| Race/Ethnicity, Customized(Count of Participants) | All Study Participants |
|---|---|
| American Indian or Alaska Native | 1 |
| Black or African American | 5 |
| White/ Caucasian/ European Heritage | 14 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Data sharing details ↗ · clinicalstudydatarequest.com
Ran from Jan 2018 to primary completion in Mar 2018, 1 month.
Results were first posted in Jun 2019, 1 year 2 months after primary completion.
Of 138 industry-sponsored phase 1 interventional studies under Pulmonary Disease, Chronic Obstructive, half reached primary completion within 4 months of starting (the median), counting those still running; a quarter within 2 and three quarters within 8. This study's 1 month is below that.
Counting every sponsor, half of 153 studies reached it within 4 months; a quarter within 2 and three quarters within 10.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Nemiralisib · Itraconazole
Pulmonary Disease, Chronic Obstructive →