Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Nemiralisib, Pharmacokinetics, Itraconazole, Drug-drug Interaction, Cross-over
Brief summary
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.
Interventions
DRUGNemiralisib
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.
DRUGItraconazole
Itraconazole will be given as 100 mg per capsule per day administered orally with water
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will be an open-label study. Hence, there will be no masking.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects must be 18 to 75 years of age inclusive, at the time of signing the informed consent. * Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac evaluation. * Normal spirometry at Screening (FEV1 and forced vital capacity \[FVC\] \>=80 percent of predicted. Measurements to be taken in triplicate. The highest value of each individual component must be \>=80 percent of predicted). * A subject with a clinical abnormality or laboratory parameter(s) (except for liver function tests) outside the reference range for the population being studied may be included only if the investigator, in consultation with the medical monitor if needed, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>50 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0 kg per meter square (kg/m\^2) (inclusive). * Male and/or female: A male subject must agree to use contraception during the treatment period and for at least 10 days after the last dose of study treatment and refrain from donating sperm during this period; a female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP). * Capable of giving signed informed consent.
Exclusion criteria
* History or presence of cardiovascular, respiratory (except childhood asthma, which has now remitted), hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data. * Abnormal blood pressure. * Liver function test results above the upper limit of normal (ULN). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * QT interval corrected for heart rate by Fridericia's formula (QTcF) \>450 milliseconds (msec). * Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing. * Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 90 days. * Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. * Current enrolment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research. * Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening. * Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. * Positive human immunodeficiency virus (HIV) antibody test (according to local policies). * Positive drug/alcohol test at screening or on admission (Day -1). * Regular use of known drugs of abuse. * Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. * Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 6 months of screening, or a total pack year history of \>5 pack years. \[number of pack years = (number of cigarettes per day/20) x number of years smoked\]. * Sensitivity to any of the study treatments, or components thereof (including lactose and Magnesium Stearate), or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study. * Unwillingness to follow the lifestyle restrictions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma | 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 | 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. |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma | 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 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma | 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 | 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 to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 35 days | 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. |
| Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Baseline (Day -1) and Day 6 | 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. |
| 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 | Baseline (Day -1), Day 2, 4, 6, 8 and 10 | 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. |
| 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) | Baseline and Day 6 | 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. |
| 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 | Baseline, Day 2, 4, 6, 8 and 10 | 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. |
| Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Baseline and Day 6 | 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. |
| Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Baseline, Day 2, 4, 6, 8 and 10 | 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. |
| Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Baseline, Day 2, 4, 6, 8 and 10 | 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. |
| 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) | Baseline and Day 6 | 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. |
| 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 | Baseline and Day 10 | 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. |
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Baseline and Day 10 | 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. |
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Baseline and Day 10 | 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. |
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Baseline and Day 10 | 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. |
| Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Baseline and Day 10 | 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. |
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered | Baseline and Day 6 | 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. |
| Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | Baseline and Day 10 | 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. |
| Specific Gravity at Indicated Time Points | Days -1, 6 and 10 | 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. |
| Number of Participants With Abnormal Urinalysis Parameter | Days -1, 6 and 10 | 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. |
| Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, 6 and 10 | 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). |
| Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Day -1 | 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). |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1: Up to Day 6; Period 2: Up to Day 10 | 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. |
| Number of Participants With Abnormal Spirometry Values | Period 1: Day -1; Period 2: Day 4 | Spirometry assessments were planned but not performed. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Baseline (Day 1, pre-dose) and Day 6 | 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. |
| Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 | 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. |
| Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Baseline (Day 1, pre-dose) and Day 6 | 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. |
| Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10 | 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. |
| Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Baseline (Day 1, pre-dose) and Day 6 | 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. |
| Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 | 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. |
| Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | Baseline (Day 1, pre-dose) and Day 6 | 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. |
| AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | 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 | 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. |
| Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10 | 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. |
| AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | 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 | 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. |
| Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | 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 | 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. |
| T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | 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 | 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. |
| Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 20 participants were enrolled at a single center in the United States.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 12.37 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Count of Participants |
| Race/Ethnicity, Customized Black or African American | 5 Count of Participants |
| Race/Ethnicity, Customized White/ Caucasian/ European Heritage | 14 Count of Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 1 / 20 | 4 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
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.
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
Population: Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma | Day 1, n=20, 0 | 40.03 Hours | Geometric Coefficient of Variation 21.7 |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma | Day 5, n=0, 14 | 64.00 Hours | Geometric Coefficient of Variation 11.4 |
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.
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
Population: Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma | Day 1, n=20, 0 | 3199.0 Hours*picogram per milliliter | Geometric Coefficient of Variation 29.8 |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma | Day 5, n=0, 14 | 6272.7 Hours*picogram per milliliter | Geometric Coefficient of Variation 27.5 |
90% CI: [1.807, 2.224]
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.
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
Population: Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma | Day 1; n=20, 0 | 2677.1 Hour*picogram per milliliter | Geometric Coefficient of Variation 30.2 |
| Itraconazole 200 mg and 100mcg Nemiralisib 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 | Day 5; n=0, 20 | 4802.3 Hour*picogram per milliliter | Geometric Coefficient of Variation 29.1 |
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.
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
Population: Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma | Day 1; n=20, 0 | 478.7 Picogram per milliliter | Geometric Coefficient of Variation 41.9 |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma | Day 5; n=0, 20 | 384.0 Picogram per milliliter | Geometric Coefficient of Variation 34 |
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.
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
Population: Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nemiralisib 100 mcg | Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma | Day 1; n=20, 0 | 0.070 Hour |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma | Day 5; n=0, 20 | 0.088 Hour |
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.
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 1 | 1201.3 Hour*nanogram per milliliter | Geometric Coefficient of Variation 46.3 |
| Nemiralisib 100 mcg | AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 5 | NA Hour*nanogram per milliliter | — |
| Nemiralisib 100 mcg | AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 1 | NA Hour*nanogram per milliliter | — |
| Nemiralisib 100 mcg | AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 5 | NA Hour*nanogram per milliliter | — |
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.
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
Population: Pharmacokinetic population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 1 | 891.7 Hour*nanogram per milliliter | Geometric Coefficient of Variation 60 |
| Nemiralisib 100 mcg | AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 5 | 4939.6 Hour*nanogram per milliliter | Geometric Coefficient of Variation 60.2 |
| Nemiralisib 100 mcg | AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 1 | 1862.6 Hour*nanogram per milliliter | Geometric Coefficient of Variation 48.8 |
| Nemiralisib 100 mcg | AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 5 | 10106.4 Hour*nanogram per milliliter | Geometric Coefficient of Variation 50.3 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.03 Picograms per liter | Standard Deviation 0.459 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.47 Femtoliter | Standard Deviation 0.889 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered | 1.94 Percentage of red blood cells in blood | Standard Deviation 2.067 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 0.14 Percentage of red blood cells in blood | Standard Deviation 1.436 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | 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) | Lymphocytes | -0.264 10^9 cells per liter | Standard Deviation 0.579 |
| Nemiralisib 100 mcg | 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) | Neutrophils | 0.198 10^9 cells per liter | Standard Deviation 0.736 |
| Nemiralisib 100 mcg | 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) | Platelets | 8.4 10^9 cells per liter | Standard Deviation 31.74 |
| Nemiralisib 100 mcg | 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) | Basophils | 0.003 10^9 cells per liter | Standard Deviation 0.014 |
| Nemiralisib 100 mcg | 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) | Eosinophils | -0.038 10^9 cells per liter | Standard Deviation 0.047 |
| Nemiralisib 100 mcg | 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) | Monocytes | -0.054 10^9 cells per liter | Standard Deviation 0.108 |
| Nemiralisib 100 mcg | 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) | Erythrocytes | 242.0 10^9 cells per liter | Standard Deviation 205.16 |
| Nemiralisib 100 mcg | 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) | WBC | -0.174 10^9 cells per liter | Standard Deviation 0.981 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | 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 | Lymphocytes | -0.202 10^9 cells per liter | Standard Deviation 0.339 |
| Nemiralisib 100 mcg | 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 | Neutrophils | -0.127 10^9 cells per liter | Standard Deviation 0.659 |
| Nemiralisib 100 mcg | 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 | Platelets | -5.7 10^9 cells per liter | Standard Deviation 28.24 |
| Nemiralisib 100 mcg | 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 | Basophils | -0.004 10^9 cells per liter | Standard Deviation 0.012 |
| Nemiralisib 100 mcg | 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 | Eosinophils | 0.003 10^9 cells per liter | Standard Deviation 0.057 |
| Nemiralisib 100 mcg | 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 | Monocytes | -0.014 10^9 cells per liter | Standard Deviation 0.13 |
| Nemiralisib 100 mcg | 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 | Erythrocytes | 76.0 10^9 cells per liter | Standard Deviation 165.83 |
| Nemiralisib 100 mcg | 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 | WBC | -0.366 10^9 cells per liter | Standard Deviation 0.846 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered | 7.3 Grams per liter | Standard Deviation 6 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 1.9 Grams per liter | Standard Deviation 4.42 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | -0.12 Picograms per liter | Standard Deviation 0.387 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | -1.09 Femtoliter | Standard Deviation 0.972 |
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.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | -1.9 Beats per minute | Standard Deviation 8.83 |
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.
Time frame: Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 10 | 2.3 Beats per minute | Standard Deviation 6.55 |
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 2 | 1.9 Beats per minute | Standard Deviation 4.8 |
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 4 | 3.2 Beats per minute | Standard Deviation 6.44 |
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 6 | 1.4 Beats per minute | Standard Deviation 6.15 |
| Nemiralisib 100 mcg | Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 8 | 3.5 Beats per minute | Standard Deviation 7.83 |
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.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | -0.4 Breaths per minute | Standard Deviation 2.01 |
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.
Time frame: Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 10 | -0.5 Breaths per minute | Standard Deviation 2.24 |
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 2 | -1.3 Breaths per minute | Standard Deviation 1.87 |
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 4 | 0.3 Breaths per minute | Standard Deviation 1.63 |
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 6 | -0.5 Breaths per minute | Standard Deviation 1.82 |
| Nemiralisib 100 mcg | Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 8 | 0.1 Breaths per minute | Standard Deviation 1.77 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered | -0.038 Percentage | Standard Deviation 0.302 |
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.
Time frame: Baseline and Day 10
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg | 0.065 Percentage | Standard Deviation 0.267 |
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.
Time frame: Baseline (Day 1, pre-dose) and Days 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | SBP, Day 2 | 0.2 Millimeter of mercury | Standard Deviation 3.71 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | SBP, Day 10 | 1.4 Millimeter of mercury | Standard Deviation 6.86 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | DBP, Day 2 | -1.0 Millimeter of mercury | Standard Deviation 3.04 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | DBP, Day 4 | -0.7 Millimeter of mercury | Standard Deviation 6.21 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | SBP, Day 4 | -1.2 Millimeter of mercury | Standard Deviation 6.37 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | SBP, Day 6 | -2.6 Millimeter of mercury | Standard Deviation 5.6 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | SBP, Day 8 | -1.8 Millimeter of mercury | Standard Deviation 6.15 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | DBP, Day 6 | -3.5 Millimeter of mercury | Standard Deviation 4.16 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | DBP, Day 8 | -3.4 Millimeter of mercury | Standard Deviation 3.39 |
| Nemiralisib 100 mcg | Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | DBP, Day 10 | -0.5 Millimeter of mercury | Standard Deviation 3.52 |
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.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | SBP | -1.2 Millimeter of mercury | Standard Deviation 4.21 |
| Nemiralisib 100 mcg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | DBP | -0.5 Millimeter of mercury | Standard Deviation 3.71 |
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.
Time frame: Baseline (Day 1, pre-dose) and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | 0.04 Celsius | Standard Deviation 0.188 |
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.
Time frame: Baseline (Day 1, pre-dose), Days 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 2 | -0.03 Celsius | Standard Deviation 0.205 |
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 4 | -0.07 Celsius | Standard Deviation 0.239 |
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 6 | -0.03 Celsius | Standard Deviation 0.266 |
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 8 | -0.08 Celsius | Standard Deviation 0.234 |
| Nemiralisib 100 mcg | Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 10 | -0.07 Celsius | Standard Deviation 0.213 |
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.
Time frame: Baseline, Day 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 2 | 0.428 Micromoles per liter | Standard Deviation 2.767 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 4 | 1.796 Micromoles per liter | Standard Deviation 2.571 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 6 | 2.907 Micromoles per liter | Standard Deviation 2.9928 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 8 | 2.309 Micromoles per liter | Standard Deviation 2.6766 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Bilirubin, Day 10 | 3.506 Micromoles per liter | Standard Deviation 2.7447 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 2 | 2.907 Micromoles per liter | Standard Deviation 0.9768 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 4 | 2.394 Micromoles per liter | Standard Deviation 1.023 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 6 | 1.796 Micromoles per liter | Standard Deviation 0.8728 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 8 | 2.052 Micromoles per liter | Standard Deviation 0.7018 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin, Day 10 | 2.907 Micromoles per liter | Standard Deviation 1.3702 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 2 | 0.442 Micromoles per liter | Standard Deviation 8.8284 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 4 | 2.210 Micromoles per liter | Standard Deviation 7.5202 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 6 | 0.884 Micromoles per liter | Standard Deviation 7.5338 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 8 | 0.442 Micromoles per liter | Standard Deviation 7.8414 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine | Creatinine, Day 10 | 0.000 Micromoles per liter | Standard Deviation 8.6042 |
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.
Time frame: Baseline, Day 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | 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 | Alkaline phosphate, Day 2 | -7.0 International Units/ Liter | Standard Deviation 6.99 |
| Nemiralisib 100 mcg | 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 | Alkaline phosphate, Day 4 | -8.5 International Units/ Liter | Standard Deviation 7 |
| Nemiralisib 100 mcg | 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 | Alkaline phosphate, Day 6 | -7.2 International Units/ Liter | Standard Deviation 9.09 |
| Nemiralisib 100 mcg | 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 | Alkaline phosphate, Day 8 | -7.6 International Units/ Liter | Standard Deviation 8.02 |
| Nemiralisib 100 mcg | 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 | Alkaline phosphate, Day 10 | -5.3 International Units/ Liter | Standard Deviation 9.35 |
| Nemiralisib 100 mcg | 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 | ALT, Day 2 | -3.2 International Units/ Liter | Standard Deviation 4.46 |
| Nemiralisib 100 mcg | 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 | ALT, Day 4 | -3.2 International Units/ Liter | Standard Deviation 3.82 |
| Nemiralisib 100 mcg | 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 | ALT, Day 6 | -2.9 International Units/ Liter | Standard Deviation 3.11 |
| Nemiralisib 100 mcg | 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 | ALT, Day 8 | -2.6 International Units/ Liter | Standard Deviation 2.96 |
| Nemiralisib 100 mcg | 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 | ALT, Day 10 | -2.8 International Units/ Liter | Standard Deviation 4.79 |
| Nemiralisib 100 mcg | 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 | AST, Day 2 | -2.6 International Units/ Liter | Standard Deviation 3.82 |
| Nemiralisib 100 mcg | 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 | AST, Day 4 | -3.0 International Units/ Liter | Standard Deviation 3.18 |
| Nemiralisib 100 mcg | 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 | AST, Day 6 | -2.4 International Units/ Liter | Standard Deviation 2.96 |
| Nemiralisib 100 mcg | 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 | AST, Day 8 | -3.2 International Units/ Liter | Standard Deviation 2.91 |
| Nemiralisib 100 mcg | 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 | AST, Day 10 | -2.0 International Units/ Liter | Standard Deviation 3.87 |
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.
Time frame: Baseline (Day -1), Day 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | 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 | Potassium, Day 10 | 0.20 Millimoles/Liter | Standard Deviation 0.339 |
| Nemiralisib 100 mcg | 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 | Sodium, Day 2 | -1.0 Millimoles/Liter | Standard Deviation 1.59 |
| Nemiralisib 100 mcg | 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 | Sodium, Day 4 | 0.0 Millimoles/Liter | Standard Deviation 2.55 |
| Nemiralisib 100 mcg | 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 | Sodium, Day 6 | -1.6 Millimoles/Liter | Standard Deviation 1.73 |
| Nemiralisib 100 mcg | 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 | Sodium, Day 8 | -1.0 Millimoles/Liter | Standard Deviation 1.72 |
| Nemiralisib 100 mcg | 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 | Sodium, Day 10 | -1.6 Millimoles/Liter | Standard Deviation 2.09 |
| Nemiralisib 100 mcg | 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 | Glucose, Day 2 | -0.08 Millimoles/Liter | Standard Deviation 0.256 |
| Nemiralisib 100 mcg | 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 | Glucose, Day 4 | -0.12 Millimoles/Liter | Standard Deviation 0.291 |
| Nemiralisib 100 mcg | 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 | Glucose, Day 6 | 1.22 Millimoles/Liter | Standard Deviation 1.055 |
| Nemiralisib 100 mcg | 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 | Glucose, Day 8 | -0.22 Millimoles/Liter | Standard Deviation 0.346 |
| Nemiralisib 100 mcg | 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 | Glucose, Day 10 | -0.22 Millimoles/Liter | Standard Deviation 0.28 |
| Nemiralisib 100 mcg | 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 | Calcium, Day 2 | 0.02 Millimoles/Liter | Standard Deviation 0.066 |
| Nemiralisib 100 mcg | 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 | Calcium, Day 4 | 0.03 Millimoles/Liter | Standard Deviation 0.069 |
| Nemiralisib 100 mcg | 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 | Calcium, Day 6 | 0.05 Millimoles/Liter | Standard Deviation 0.081 |
| Nemiralisib 100 mcg | 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 | Calcium, Day 8 | 0.00 Millimoles/Liter | Standard Deviation 0.077 |
| Nemiralisib 100 mcg | 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 | Calcium, Day 10 | 0.03 Millimoles/Liter | Standard Deviation 0.059 |
| Nemiralisib 100 mcg | 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 | Potassium, Day 2 | 0.07 Millimoles/Liter | Standard Deviation 0.326 |
| Nemiralisib 100 mcg | 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 | Potassium, Day 4 | 0.29 Millimoles/Liter | Standard Deviation 0.381 |
| Nemiralisib 100 mcg | 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 | Potassium, Day 6 | 0.01 Millimoles/Liter | Standard Deviation 0.348 |
| Nemiralisib 100 mcg | 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 | Potassium, Day 8 | 0.21 Millimoles/Liter | Standard Deviation 0.323 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | 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) | Alkaline phosphate | 0.8 International Units/ Liter | Standard Deviation 8.08 |
| Nemiralisib 100 mcg | 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) | ALT | 1.5 International Units/ Liter | Standard Deviation 7.4 |
| Nemiralisib 100 mcg | 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) | AST | -0.5 International Units/ Liter | Standard Deviation 3.4 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Bilirubin | 5.557 Micromoles per liter | Standard Deviation 7.231 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Direct bilirubin | 2.394 Micromoles per liter | Standard Deviation 0.8595 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine | Creatinine | -3.094 Micromoles per liter | Standard Deviation 6.5872 |
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.
Time frame: Baseline (Day -1) and Day 6
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Glucose | -0.12 Millimoles/Liter | Standard Deviation 0.247 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Calcium | 0.06 Millimoles/Liter | Standard Deviation 0.07 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Potassium | 0.20 Millimoles/Liter | Standard Deviation 0.29 |
| Nemiralisib 100 mcg | Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium | Sodium | -0.9 Millimoles/Liter | Standard Deviation 2.05 |
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.
Time frame: Baseline, Day 2, 4, 6, 8 and 10
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 2 | -3.8 Gram per liter | Standard Deviation 3.52 |
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 4 | -3.4 Gram per liter | Standard Deviation 3.03 |
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 6 | 0.2 Gram per liter | Standard Deviation 3.74 |
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 8 | -2.4 Gram per liter | Standard Deviation 3.86 |
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose | Day 10 | -1.8 Gram per liter | Standard Deviation 2.95 |
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.
Time frame: Baseline and Day 6
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nemiralisib 100 mcg | Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered | 3.3 Gram per liter | Standard Deviation 3.85 |
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.
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
Population: Pharmacokinetic population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 1 | 156.90 Nanogram per milliliter | Geometric Coefficient of Variation 59 |
| Nemiralisib 100 mcg | Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 5 | 472.52 Nanogram per milliliter | Geometric Coefficient of Variation 63.7 |
| Nemiralisib 100 mcg | Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 1 | 240.3 Nanogram per milliliter | Geometric Coefficient of Variation 45.2 |
| Nemiralisib 100 mcg | Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 5 | 541.2 Nanogram per milliliter | Geometric Coefficient of Variation 41.8 |
90% CI: [0.69, 0.933]
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.
Time frame: Period 1: Up to Day 6; Period 2: Up to Day 10
Population: Safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemiralisib 100 mcg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
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).
Time frame: Day -1
Population: Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast10, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Epithelial cells 0, n=2,2 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast0, n=2,2 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Epithelial cells 1, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 3, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 1, n=2,2 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast2, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 7, n=2,2 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Leukocytes 2, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 9, n=2,2 | 0 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Leukocytes 1, n=2,2 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast3, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Leukocytes 1, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 3, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 9, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Leukocytes 2, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast0, n=2,2 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast2, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast10, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Epithelial cells 0, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Epithelial cells 1, n=2,2 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 1, n=2,2 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Erythrocytes 7, n=2,2 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes | Cast3, n=2,2 | 0 Participants |
Secondary
Number of Participants With Abnormal Spirometry Values
Spirometry assessments were planned but not performed.
Time frame: Period 1: Day -1; Period 2: Day 4
Population: Safety population.
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.
Time frame: Days -1, 6 and 10
Population: Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Ketones, Day -1, Trace, n=20,19 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Erythrocytes, Day-1,Trace, n=20,19 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Erythrocytes, Day-1,2+, n=20,19 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Leukocytes, Day 6, Trace, n=20,0 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Leukocytes, Day 6, 2+, n=20,0 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Abnormal Urinalysis Parameter | Protein, Day -1, Trace, n=20,19 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Urinalysis Parameter | Ketones, Day -1, Trace, n=20,19 | 2 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Urinalysis Parameter | Erythrocytes, Day-1,Trace, n=20,19 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Urinalysis Parameter | Protein, Day -1, Trace, n=20,19 | 1 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Abnormal Urinalysis Parameter | Erythrocytes, Day-1,2+, n=20,19 | 1 Participants |
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.
Time frame: Up to 35 days
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemiralisib 100 mcg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 4 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
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).
Time frame: Day -1, 6 and 10
Population: Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=7, n=20,19 | 2 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 6, pH=5, n=20,0 | 9 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 6, pH=6, n=20,0 | 8 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 6, pH=7, n=20,0 | 3 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=8, n=20,19 | 1 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=6, n=20,19 | 9 Participants |
| Nemiralisib 100 mcg | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=5, n=20,19 | 8 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 10, pH=7, n=0,20 | 7 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=6, n=20,19 | 8 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=8, n=20,19 | 0 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=7, n=20,19 | 3 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 10, pH=5, n=0,20 | 9 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day 10, pH=6, n=0,20 | 4 Participants |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, pH=5, n=20,19 | 8 Participants |
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.
Time frame: Days -1, 6 and 10
Population: Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | Specific Gravity at Indicated Time Points | Day -1, n=20, 19 | 1.0198 Grams per cubic centimeter | Standard Deviation 0.00713 |
| Nemiralisib 100 mcg | Specific Gravity at Indicated Time Points | Day 6, n=20, 0 | 1.0188 Grams per cubic centimeter | Standard Deviation 0.00614 |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Specific Gravity at Indicated Time Points | Day -1, n=20, 19 | 1.0207 Grams per cubic centimeter | Standard Deviation 0.00863 |
| Itraconazole 200 mg and 100mcg Nemiralisib on Day 5 | Specific Gravity at Indicated Time Points | Day 10, n=0, 20 | 1.0175 Grams per cubic centimeter | Standard Deviation 0.00583 |
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.
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemiralisib 100 mcg | T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 1 | 3.865 Hour | Geometric Coefficient of Variation 7.7 |
| Nemiralisib 100 mcg | T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 5 | NA Hour | — |
| Nemiralisib 100 mcg | T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 1 | NA Hour | — |
| Nemiralisib 100 mcg | T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 5 | NA Hour | — |
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.
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
Population: Pharmacokinetic population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nemiralisib 100 mcg | Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 1 | 4.001 Hour |
| Nemiralisib 100 mcg | Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Itraconazole, Day 5 | 4.001 Hour |
| Nemiralisib 100 mcg | Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 1 | 4.004 Hour |
| Nemiralisib 100 mcg | Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2 | Hydroxy Itraconazole, Day 5 | 4.004 Hour |