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A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics (PK) of Nemiralisib

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ClinicalTrials.gov Identifier: NCT03398421
Recruitment Status : Completed
First Posted : January 12, 2018
Results First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Nemiralisib
Drug: Itraconazole
Enrollment 20
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.
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 Milligram(mg) With 100mcg Nemiralisib
Hide Arm/Group Description Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days. After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Period Title: Treatment Period 1 (Up to 6 Days)
Started 20 0
Completed 20 0
Not Completed 0 0
Period Title: Washout Period (Up to 14 Days)
Started 20 0
Completed 20 0
Not Completed 0 0
Period Title: Treatment Period 2 (Up to 11 Days)
Started 0 20
Completed 0 20
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
36.1  (12.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
0
   0.0%
Male
20
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 20 participants
American Indian or Alaska Native 1
Black or African American 5
White/ Caucasian/ European Heritage 14
1.Primary Outcome
Title Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*picogram per milliliter
Day 1, n=20, 0 Number Analyzed 20 participants 0 participants
3199.0
(29.8%)
Day 5, n=0, 14 Number Analyzed 0 participants 14 participants
6272.7
(27.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nemiralisib 100 mcg, Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric mean
Estimated Value 2.005
Confidence Interval (2-Sided) 90%
1.807 to 2.224
Estimation Comments [Not Specified]
2.Primary Outcome
Title Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*picogram per milliliter
Day 1; n=20, 0 Number Analyzed 20 participants 0 participants
2677.1
(30.2%)
Day 5; n=0, 20 Number Analyzed 0 participants 20 participants
4802.3
(29.1%)
3.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram per milliliter
Day 1; n=20, 0 Number Analyzed 20 participants 0 participants
478.7
(41.9%)
Day 5; n=0, 20 Number Analyzed 0 participants 20 participants
384.0
(34.0%)
4.Primary Outcome
Title Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
Day 1, n=20, 0 Number Analyzed 20 participants 0 participants
40.03
(21.7%)
Day 5, n=0, 14 Number Analyzed 0 participants 14 participants
64.00
(11.4%)
5.Primary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Median (Full Range)
Unit of Measure: Hour
Day 1; n=20, 0 Number Analyzed 20 participants 0 participants
0.070
(0.07 to 0.08)
Day 5; n=0, 20 Number Analyzed 0 participants 20 participants
0.088
(0.08 to 0.10)
6.Secondary Outcome
Title AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nemiralisib 100 mcg With Itraconazole 200 mg
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*nanogram per milliliter
Itraconazole, Day 1 Number Analyzed 7 participants
1201.3
(46.3%)
Itraconazole, Day 5 Number Analyzed 7 participants
NA [1] 
(NA%)
Hydroxy Itraconazole, Day 1 Number Analyzed 7 participants
NA [1] 
(NA%)
Hydroxy Itraconazole, Day 5 Number Analyzed 20 participants
NA [1] 
(NA%)
[1]
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.
7.Secondary Outcome
Title AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*nanogram per milliliter
Itraconazole, Day 1
891.7
(60.0%)
Itraconazole, Day 5
4939.6
(60.2%)
Hydroxy Itraconazole, Day 1
1862.6
(48.8%)
Hydroxy Itraconazole, Day 5
10106.4
(50.3%)
8.Secondary Outcome
Title Cmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
Itraconazole, Day 1
156.90
(59.0%)
Itraconazole, Day 5
472.52
(63.7%)
Hydroxy Itraconazole, Day 1
240.3
(45.2%)
Hydroxy Itraconazole, Day 5
541.2
(41.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric mean
Estimated Value 0.802
Confidence Interval (2-Sided) 90%
0.690 to 0.933
Estimation Comments [Not Specified]
9.Secondary Outcome
Title T1/2 of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour
Itraconazole, Day 1
3.865
(7.7%)
Itraconazole, Day 5
NA [1] 
(NA%)
Hydroxy Itraconazole, Day 1
NA [1] 
(NA%)
Hydroxy Itraconazole, Day 5
NA [1] 
(NA%)
[1]
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.
10.Secondary Outcome
Title Tmax of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: Hour
Itraconazole, Day 1
4.001
(2.00 to 6.00)
Itraconazole, Day 5
4.001
(2.00 to 6.00)
Hydroxy Itraconazole, Day 1
4.004
(3.00 to 6.01)
Hydroxy Itraconazole, Day 5
4.004
(3.00 to 8.01)
11.Secondary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
1
   5.0%
4
  20.0%
Any SAE
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered: Calcium, Glucose, Potassium and Sodium
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Millimoles/Liter
Glucose -0.12  (0.247)
Calcium 0.06  (0.070)
Potassium 0.20  (0.290)
Sodium -0.9  (2.05)
13.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg With Itraconazole 200 mg
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Millimoles/Liter
Glucose, Day 2 -0.08  (0.256)
Glucose, Day 4 -0.12  (0.291)
Glucose, Day 6 1.22  (1.055)
Glucose, Day 8 -0.22  (0.346)
Glucose, Day 10 -0.22  (0.280)
Calcium, Day 2 0.02  (0.066)
Calcium, Day 4 0.03  (0.069)
Calcium, Day 6 0.05  (0.081)
Calcium, Day 8 0.00  (0.077)
Calcium, Day 10 0.03  (0.059)
Potassium, Day 2 0.07  (0.326)
Potassium, Day 4 0.29  (0.381)
Potassium, Day 6 0.01  (0.348)
Potassium, Day 8 0.21  (0.323)
Potassium, Day 10 0.20  (0.339)
Sodium, Day 2 -1.0  (1.59)
Sodium, Day 4 0.0  (2.55)
Sodium, Day 6 -1.6  (1.73)
Sodium, Day 8 -1.0  (1.72)
Sodium, Day 10 -1.6  (2.09)
14.Secondary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: International Units/ Liter
Alkaline phosphate 0.8  (8.08)
ALT 1.5  (7.40)
AST -0.5  (3.40)
15.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: International Units/ Liter
Alkaline phosphate, Day 2 -7.0  (6.99)
Alkaline phosphate, Day 4 -8.5  (7.00)
Alkaline phosphate, Day 6 -7.2  (9.09)
Alkaline phosphate, Day 8 -7.6  (8.02)
Alkaline phosphate, Day 10 -5.3  (9.35)
ALT, Day 2 -3.2  (4.46)
ALT, Day 4 -3.2  (3.82)
ALT, Day 6 -2.9  (3.11)
ALT, Day 8 -2.6  (2.96)
ALT, Day 10 -2.8  (4.79)
AST, Day 2 -2.6  (3.82)
AST, Day 4 -3.0  (3.18)
AST, Day 6 -2.4  (2.96)
AST, Day 8 -3.2  (2.91)
AST, Day 10 -2.0  (3.87)
16.Secondary Outcome
Title Change From Baseline of Clinical Chemistry Parameters When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered:Bilirubin, Direct Bilirubin and Creatinine
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter
Bilirubin 5.557  (7.2310)
Direct bilirubin 2.394  (0.8595)
Creatinine -3.094  (6.5872)
17.Secondary Outcome
Title Change From Baseline of Clinical Chemistry Parameters When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose: Bilirubin, Direct Bilirubin and Creatinine
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter
Bilirubin, Day 2 0.428  (2.7670)
Bilirubin, Day 4 1.796  (2.5710)
Bilirubin, Day 6 2.907  (2.9928)
Bilirubin, Day 8 2.309  (2.6766)
Bilirubin, Day 10 3.506  (2.7447)
Direct bilirubin, Day 2 2.907  (0.9768)
Direct bilirubin, Day 4 2.394  (1.0230)
Direct bilirubin, Day 6 1.796  (0.8728)
Direct bilirubin, Day 8 2.052  (0.7018)
Direct bilirubin, Day 10 2.907  (1.3702)
Creatinine, Day 2 0.442  (8.8284)
Creatinine, Day 4 2.210  (7.5202)
Creatinine, Day 6 0.884  (7.5338)
Creatinine, Day 8 0.442  (7.8414)
Creatinine, Day 10 0.000  (8.6042)
18.Secondary Outcome
Title Change From Baseline of Total Protein When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Gram per liter
3.3  (3.85)
19.Secondary Outcome
Title Change From Baseline of Total Protein When Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Gram per liter
Day 2 -3.8  (3.52)
Day 4 -3.4  (3.03)
Day 6 0.2  (3.74)
Day 8 -2.4  (3.86)
Day 10 -1.8  (2.95)
20.Secondary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter
Lymphocytes -0.264  (0.579)
Neutrophils 0.198  (0.736)
Platelets 8.4  (31.74)
Basophils 0.003  (0.014)
Eosinophils -0.038  (0.047)
Monocytes -0.054  (0.108)
Erythrocytes 242.0  (205.16)
WBC -0.174  (0.981)
21.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter
Lymphocytes -0.202  (0.339)
Neutrophils -0.127  (0.659)
Platelets -5.7  (28.24)
Basophils -0.004  (0.012)
Eosinophils 0.003  (0.057)
Monocytes -0.014  (0.130)
Erythrocytes 76.0  (165.83)
WBC -0.366  (0.846)
22.Secondary Outcome
Title Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Percentage of red blood cells in blood
1.94  (2.067)
23.Secondary Outcome
Title Change From Baseline in Hematocrit When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Percentage of red blood cells in blood
0.14  (1.436)
24.Secondary Outcome
Title Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Grams per liter
7.3  (6.00)
25.Secondary Outcome
Title Change From Baseline in Hemoglobin When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Grams per liter
1.9  (4.42)
26.Secondary Outcome
Title Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (MCH) When Single Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Picograms per liter
-0.03  (0.459)
27.Secondary Outcome
Title Change From Baseline in MCH When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Picograms per liter
-0.12  (0.387)
28.Secondary Outcome
Title Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) When Single Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Femtoliter
-0.47  (0.889)
29.Secondary Outcome
Title Change From Baseline in MCV When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Femtoliter
-1.09  (0.972)
30.Secondary Outcome
Title Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Percentage
-0.038  (0.302)
31.Secondary Outcome
Title Change From Baseline in Reticulocyte Percentage When Single Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Percentage
0.065  (0.267)
32.Secondary Outcome
Title Specific Gravity at Indicated Time Points
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: Grams per cubic centimeter
Day -1, n=20, 19 Number Analyzed 20 participants 19 participants
1.0198  (0.00713) 1.0207  (0.00863)
Day 6, n=20, 0 Number Analyzed 20 participants 0 participants
1.0188  (0.00614)
Day 10, n=0, 20 Number Analyzed 0 participants 20 participants
1.0175  (0.00583)
33.Secondary Outcome
Title Number of Participants With Abnormal Urinalysis Parameter
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
Ketones, Day -1, Trace, n=20,19 Number Analyzed 20 participants 19 participants
2
  10.0%
2
  10.5%
Protein, Day -1, Trace, n=20,19 Number Analyzed 20 participants 19 participants
0
   0.0%
1
   5.3%
Erythrocytes, Day-1,Trace, n=20,19 Number Analyzed 20 participants 19 participants
1
   5.0%
0
   0.0%
Erythrocytes, Day-1,2+, n=20,19 Number Analyzed 20 participants 19 participants
1
   5.0%
1
   5.3%
Leukocytes, Day 6, Trace, n=20,0 Number Analyzed 20 participants 0 participants
2
  10.0%
Leukocytes, Day 6, 2+, n=20,0 Number Analyzed 20 participants 0 participants
1
   5.0%
34.Secondary Outcome
Title Number of Participants With Urine Potential of Hydrogen (pH) at Indicated Time Points
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
Day -1, pH=5, n=20,19 Number Analyzed 20 participants 19 participants
8
  40.0%
8
  42.1%
Day -1, pH=6, n=20,19 Number Analyzed 20 participants 19 participants
9
  45.0%
8
  42.1%
Day -1, pH=7, n=20,19 Number Analyzed 20 participants 19 participants
2
  10.0%
3
  15.8%
Day -1, pH=8, n=20,19 Number Analyzed 20 participants 19 participants
1
   5.0%
0
   0.0%
Day 6, pH=5, n=20,0 Number Analyzed 20 participants 0 participants
9
  45.0%
Day 6, pH=6, n=20,0 Number Analyzed 20 participants 0 participants
8
  40.0%
Day 6, pH=7, n=20,0 Number Analyzed 20 participants 0 participants
3
  15.0%
Day 10, pH=5, n=0,20 Number Analyzed 0 participants 20 participants
9
  45.0%
Day 10, pH=6, n=0,20 Number Analyzed 0 participants 20 participants
4
  20.0%
Day 10, pH=7, n=0,20 Number Analyzed 0 participants 20 participants
7
  35.0%
35.Secondary Outcome
Title Number of Participants With Abnormal Microscopic Examinations: Casts, Epithelial Cells, Erythrocytes and Leukocytes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
Cast0, n=2,2 Number Analyzed 2 participants 2 participants
1
  50.0%
0
   0.0%
Cast2, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Cast3, n=2,2 Number Analyzed 2 participants 2 participants
1
  50.0%
0
   0.0%
Cast10, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Epithelial cells 0, n=2,2 Number Analyzed 2 participants 2 participants
2
 100.0%
1
  50.0%
Epithelial cells 1, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Erythrocytes 1, n=2,2 Number Analyzed 2 participants 2 participants
1
  50.0%
0
   0.0%
Erythrocytes 3, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Erythrocytes 7, n=2,2 Number Analyzed 2 participants 2 participants
1
  50.0%
0
   0.0%
Erythrocytes 9, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Leukocytes 1, n=2,2 Number Analyzed 2 participants 2 participants
2
 100.0%
1
  50.0%
Leukocytes 2, n=2,2 Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
36.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
37.Secondary Outcome
Title Number of Participants With Abnormal Spirometry Values
Hide Description Spirometry assessments were planned but not performed.
Time Frame Period 1: Day -1; Period 2: Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
38.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury
SBP -1.2  (4.21)
DBP -0.5  (3.71)
39.Secondary Outcome
Title Change From Baseline in SBP and DBP When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury
SBP, Day 2 0.2  (3.71)
SBP, Day 4 -1.2  (6.37)
SBP, Day 6 -2.6  (5.60)
SBP, Day 8 -1.8  (6.15)
SBP, Day 10 1.4  (6.86)
DBP, Day 2 -1.0  (3.04)
DBP, Day 4 -0.7  (6.21)
DBP, Day 6 -3.5  (4.16)
DBP, Day 8 -3.4  (3.39)
DBP, Day 10 -0.5  (3.52)
40.Secondary Outcome
Title Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Beats per minute
-1.9  (8.83)
41.Secondary Outcome
Title Change From Baseline in Pulse Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 2 1.9  (4.80)
Day 4 3.2  (6.44)
Day 6 1.4  (6.15)
Day 8 3.5  (7.83)
Day 10 2.3  (6.55)
42.Secondary Outcome
Title Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Breaths per minute
-0.4  (2.01)
43.Secondary Outcome
Title Change From Baseline in Respiratory Rate When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Breaths per minute
Day 2 -1.3  (1.87)
Day 4 0.3  (1.63)
Day 6 -0.5  (1.82)
Day 8 0.1  (1.77)
Day 10 -0.5  (2.24)
44.Secondary Outcome
Title Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Administered
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Nemiralisib 100 mcg
Hide Arm/Group Description:
Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Celsius
0.04  (0.188)
45.Secondary Outcome
Title Change From Baseline in Temperature When Single Inhaled Oral Dose of Nemiralisib 100 mcg Co-administered With Itraconazole 200 mg Repeated Dose
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Itraconazole 200 mg and 100mcg Nemiralisib on Day 5
Hide Arm/Group Description:
After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: Celsius
Day 2 -0.03  (0.205)
Day 4 -0.07  (0.239)
Day 6 -0.03  (0.266)
Day 8 -0.08  (0.234)
Day 10 -0.07  (0.213)
Time Frame Serious adverse events (SAEs) and adverse events (AEs) were collected up to Day 35
Adverse Event Reporting Description AEs and SAEs were collected in the Safety Population.
 
Arm/Group Title Nemiralisib 100 mcg Nemiralisib 100 mcg With Itraconazole 200 mg
Hide Arm/Group Description Participants received a single inhaled oral dose of 100 microgram (mcg) nemiralisib on Day 1 of Period 1 followed by a washout period of 14 days. After a washout period of 14 days, participants received a single oral dose of 200 mg Itraconazole from Days 1 to 10. On Day 5, they received a single inhaled oral dose of 100 mcg nemiralisib one hour after the dose of 200 mg Itraconazole.
All-Cause Mortality
Nemiralisib 100 mcg Nemiralisib 100 mcg With Itraconazole 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/20 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Nemiralisib 100 mcg Nemiralisib 100 mcg With Itraconazole 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/20 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Nemiralisib 100 mcg Nemiralisib 100 mcg With Itraconazole 200 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   1/20 (5.00%)   4/20 (20.00%) 
Ear and labyrinth disorders     
Hypoacusis  1  0/20 (0.00%)  1/20 (5.00%) 
Eye disorders     
Dry eye  1  0/20 (0.00%)  1/20 (5.00%) 
Infections and infestations     
Viral upper respiratory tract infection  1  0/20 (0.00%)  2/20 (10.00%) 
Nervous system disorders     
Headache  1  1/20 (5.00%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03398421     History of Changes
Other Study ID Numbers: 206874
First Submitted: January 8, 2018
First Posted: January 12, 2018
Results First Submitted: February 27, 2019
Results First Posted: June 3, 2019
Last Update Posted: June 3, 2019