Download PDF

Clinical Trial Results:
A Phase IIb, Randomized (Stratified), Double-Blind (Sponsor Open), Parallel-Group, Placebo-Controlled, Dose-Finding Study of Nemiralisib (GSK2269557) Added to Standard of Care (SoC) Versus SoC Alone in Participants Diagnosed with an Acute Moderate or Severe Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)

Summary
EudraCT number	2017-001074-42
Trial protocol	NL SE GB PL DE ES IT RO
Global end of trial date	10 Jan 2019

Results information
Results version number	v1
This version publication date	18 Dec 2019
First version publication date	18 Dec 2019
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

200879

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Apr 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Jan 2019

Was the trial ended prematurely?

Main objective of the trial

To characterize the dose response of nemiralisib administered in addition to SoC compared with placebo and SoC in participants diagnosed with an acute moderate or severe exacerbation of COPD

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 103

Country: Number of subjects enrolled

Australia: 18

Country: Number of subjects enrolled

Canada: 27

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 84

Country: Number of subjects enrolled

Italy: 43

Country: Number of subjects enrolled

Korea, Republic of: 68

Country: Number of subjects enrolled

Mexico: 16

Country: Number of subjects enrolled

Netherlands: 27

Country: Number of subjects enrolled

Poland: 89

Country: Number of subjects enrolled

Romania: 88

Country: Number of subjects enrolled

Russian Federation: 101

Country: Number of subjects enrolled

Spain: 114

Country: Number of subjects enrolled

Sweden: 4

Country: Number of subjects enrolled

United Kingdom: 22

Country: Number of subjects enrolled

United States: 126

Worldwide total number of subjects

943

EEA total number of subjects

484

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

430

From 65 to 84 years

513

85 years and over

Subject disposition

Top of page

Recruitment details

This was a Phase IIb, multicenter, randomized, stratified, double-blind (sponsor open), placebo controlled parallel-group study in participants who presented with an acute moderate or severe exacerbation of chronic obstructive pulmonary disease (COPD) requiring Standard of Care (SoC).

Screening details

A total of 943 participants were randomized, and 938 participants who received at least one dose of study treatment were included in the modified intent to treat (MITT) Population. The study included participants enrolled from 16 countries.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants were administered a single oral inhalation of placebo via ELLIPTA dry powder inhaler (DPI) once daily in the morning for 12 weeks. Albuterol (salbutamol) metered-dose inhaler (MDI) or nebules were also provided to all participants as rescue medication.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received placebo as dry powder inhalation once in the morning.

Nemiralisib 12.5 mcg

Arm description

Participants were administered a single oral inhalation of 12.5 micrograms (mcg) nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration of 12.5 micrograms (mcg) as dry powder inhalation once in the morning.

Nemiralisib 50 mcg

Arm description

Participants were administered a single oral inhalation of 50 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration of 50 mcg as dry powder inhalation once in the morning.

Nemiralisib 100 mcg

Arm description

Participants were administered a single oral inhalation of 100 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration of 100 mcg as dry powder inhalation once in the morning.

Nemiralisib 250 mcg

Arm description

Participants were administered a single oral inhalation of 250 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration 250 mcg as dry powder inhalation once in the morning.

Nemiralisib 500 mcg

Arm description

Participants were administered a single oral inhalation of 500 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration of 500 mcg as dry powder inhalation once in the morning.

Nemiralisib 750 mcg

Arm description

Participants were administered a single oral inhalation of 750 mcg nemiralisib via ELLIPTA DPI once daily in the morning for 12 weeks. Albuterol (salbutamol) MDI or nebules were also provided to all participants as rescue medication.

Arm type

Active comparator

Investigational medicinal product name

Nemiralisib

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Participants received Nemiralisib at concentration of 750 mcg as dry powder inhalation once in the morning.

Number of subjects in period 1 ^[1]	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Started	276	22	91	92	90	89	278
Completed	244	19	79	81	75	73	233
Not completed	32	3	12	11	15	16	45
Consent withdrawn by subject	11	1	5	6	3	6	16
Physician decision	3	1	-	-	1	2	3
Protocol-defined stopping criteria	9	-	-	-	2	1	1
Adverse event, non-fatal	4	-	5	4	6	5	16
Lost to follow-up	2	-	1	-	1	2	3
Protocol deviation	2	-	-	-	1	-	3
Lack of efficacy	1	1	1	1	1	-	3

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 943 participants were randomized, and 938 participants who received at least one dose of study treatment were included in the MITT Population.

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Nemiralisib 12.5 mcg

Reporting group description

Reporting group title

Nemiralisib 50 mcg

Reporting group description

Reporting group title

Nemiralisib 100 mcg

Reporting group description

Reporting group title

Nemiralisib 250 mcg

Reporting group description

Reporting group title

Nemiralisib 500 mcg

Reporting group description

Reporting group title

Nemiralisib 750 mcg

Reporting group description

Reporting group values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg	Total
Number of subjects	276	22	91	92	90	89	278	938
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0
Adults (18-64 years)	123	9	44	38	39	41	134	428
From 65-84 years	153	13	47	54	51	48	144	510
85 years and over	0	0	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	65.4 ± 7.94	67.8 ± 7.20	63.1 ± 7.61	65.1 ± 7.43	66.0 ± 6.94	64.9 ± 8.04	64.8 ± 7.61	-
Sex: Female, Male
Units: Subjects
Female	86	6	35	29	31	22	100	309
Male	190	16	56	63	59	67	178	629
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	2	0	2	1	2	2	6	15
Asian-East Asian Heritage	18	4	7	2	9	7	19	66
Asian-South East Asian Heritage	1	0	0	1	0	1	1	4
Black or African American	2	1	2	1	0	2	6	14
White-Arabic/North African Heritage	1	0	1	1	0	1	0	4
White-White Caucasian/European Heritage	252	17	79	86	79	76	246	835

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Nemiralisib 12.5 mcg

Reporting group description

Reporting group title

Nemiralisib 50 mcg

Reporting group description

Reporting group title

Nemiralisib 100 mcg

Reporting group description

Reporting group title

Nemiralisib 250 mcg

Reporting group description

Reporting group title

Nemiralisib 500 mcg

Reporting group description

Reporting group title

Nemiralisib 750 mcg

Reporting group description

Primary: Change from Baseline in Clinic Visit trough forced expiratory volume in one second (FEV1) at Day 84 measured post bronchodilator

Top of page

End point title

Change from Baseline in Clinic Visit trough forced expiratory volume in one second (FEV1) at Day 84 measured post bronchodilator

End point description

Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after administration of 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via 1 nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented. Only those participants with data at specified data points were analyzed.

End point type

Primary

End point timeframe

Baseline and Day 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	215 ^[1]	16 ^[2]	72 ^[3]	75 ^[4]	69 ^[5]	58 ^[6]	216 ^[7]
Units: Liters
median (confidence interval 95%)	0.052 (0.018 to 0.091)	0.031 (-0.090 to 0.149)	0.026 (-0.036 to 0.084)	0.014 (-0.044 to 0.073)	0.058 (-0.002 to 0.118)	0.049 (-0.017 to 0.113)	0.049 (0.012 to 0.086)

Notes
[1] - MITT Population consists of randomized participants who received atleast 1 dose of study treatment.
[2] - MITT Population.
[3] - MITT Population.
[4] - MITT Population.
[5] - MITT Population.
[6] - MITT Population.
[7] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

other ^[8]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.022

Confidence interval

level

95%

sides

2-sided

lower limit

-0.143

upper limit

0.103

Notes
[8] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 12.5 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

287

Analysis specification

Pre-specified

Analysis type

other ^[9]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.027

Confidence interval

level

95%

sides

2-sided

lower limit

-0.098

upper limit

0.036

Notes
[9] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 50 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

other ^[10]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.038

Confidence interval

level

95%

sides

2-sided

lower limit

-0.102

upper limit

0.028

Notes
[10] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 100 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

284

Analysis specification

Pre-specified

Analysis type

other ^[11]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.064

upper limit

0.071

Notes
[11] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 250 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

273

Analysis specification

Pre-specified

Analysis type

other ^[12]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.075

upper limit

0.061

Notes
[12] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 500 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

431

Analysis specification

Pre-specified

Analysis type

other ^[13]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.004

Confidence interval

level

95%

sides

2-sided

lower limit

-0.051

upper limit

0.042

Notes
[13] - Treatment comparison (posterior adjusted median difference and 95% HPD CrI) of Nemiralisib 750 mcg and placebo for Day 84 change from Baseline FEV1 measured post-bronchodilator has been presented.

Secondary: Rate of moderate and severe exacerbations over 12-week treatment period

Top of page

End point title

Rate of moderate and severe exacerbations over 12-week treatment period

End point description

Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented. The participants randomized to Nemiralisib 12.5 mcg were excluded from this analysis due to insufficient participants with data.

End point type

Secondary

End point timeframe

Up to Week 12

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[14]	22 ^[15]	91 ^[16]	92 ^[17]	90 ^[18]	89 ^[19]	278 ^[20]
Units: No.of exacerbation per 84 Days
median (confidence interval 95%)	0.31 (0.25 to 0.39)	99999 (99999 to 99999)	0.29 (0.20 to 0.39)	0.28 (0.20 to 0.38)	0.32 (0.23 to 0.43)	0.20 (0.13 to 0.29)	0.36 (0.29 to 0.43)

Notes
[14] - MITT Population.
[15] - MITT Population.
[16] - MITT Population.
[17] - MITT Population.
[18] - MITT Population.
[19] - MITT Population.
[20] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[21]

Method

Parameter type

Posterior median exacerbation rate ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.4

Notes
[21] - Treatment comparison (posterior median exacerbation rate ratio and 95% HPD CrI) of Nemiralisib 50 mcg and placebo for moderate/severe exacerbations has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[22]

Method

Parameter type

Posterior median exacerbation rate ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.35

Notes
[22] - Treatment comparison (posterior median exacerbation rate ratio and 95% HPD CrI) of Nemiralisib 100 mcg and placebo for moderate/severe exacerbations has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[23]

Method

Parameter type

Posterior median exacerbation rate ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.5

Notes
[23] - Treatment comparison (posterior median exacerbation rate ratio and 95% HPD CrI) of Nemiralisib 250 mcg and placebo for moderate/severe exacerbations has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[24]

Method

Parameter type

Posterior median exacerbation rate ratio

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

1.02

Notes
[24] - Treatment comparison (posterior median exacerbation rate ratio and 95% HPD CrI) of Nemiralisib 500 mcg and placebo for moderate/severe exacerbations has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[25]

Method

Parameter type

Posterior median exacerbation rate ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.52

Notes
[25] - Treatment comparison (posterior median exacerbation rate ratio and 95% HPD CrI) of Nemiralisib 750 mcg and placebo for moderate/severe exacerbations has been presented.

Secondary: Number of participants with Time to next moderate/severe exacerbation following index exacerbation

Top of page

End point title

Number of participants with Time to next moderate/severe exacerbation following index exacerbation

End point description

Time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.

End point type

Secondary

End point timeframe

Up to Week 12

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[26]	22 ^[27]	91 ^[28]	92 ^[29]	90 ^[30]	89 ^[31]	278 ^[32]
Units: Participants	72	3	24	25	26	15	80

Notes
[26] - MITT Population.
[27] - MITT Population.
[28] - MITT Population.
[29] - MITT Population.
[30] - MITT Population.
[31] - MITT Population.
[32] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[33]

Method

Parameter type

Posterior median hazard ratio

Point estimate

0.455

Confidence interval

level

95%

sides

2-sided

lower limit

0.054

upper limit

1.103

Notes
[33] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 12.5 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

Parameter type

Posterior median hazard ratio

Point estimate

0.991

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.5

Notes
[34] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 50 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[35]

Method

Parameter type

Posterior median hazard ratio

Point estimate

0.975

Confidence interval

level

95%

sides

2-sided

lower limit

0.581

upper limit

1.467

Notes
[35] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 100 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[36]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.132

Confidence interval

level

95%

sides

2-sided

lower limit

0.682

upper limit

1.709

Notes
[36] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 250 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Parameter type

Posterior median hazard ratio

Point estimate

0.556

Confidence interval

level

95%

sides

2-sided

lower limit

0.268

upper limit

0.902

Notes
[37] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 500 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[38]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.149

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.539

Notes
[38] - Treatment comparison (Hazard Ratio and 95% HPD CrI) of Nemiralisib 750 mcg and placebo for time to next moderate/severe exacerbations has been presented.

Secondary: Change from Baseline in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Top of page

End point title

Change from Baseline in Clinic Visit trough FEV1 measured pre and post-bronchodilator

End point description

Pulmonary function was measured by FEV1. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1. Only those participants with data available at specified data points were analyzed (represented by n= X in category titles). 99999 indicates standard deviation could not be calculated as single participant was analyzed. 88888 indicates number of participants analyzed was zero.

End point type

Secondary

End point timeframe

Baseline and Days 14, 28, 56 (pre and post bronchodilaor), 84 (pre-bronchodilator) and at hospital discharge (maximum 24 Weeks)

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[39]	22 ^[40]	91 ^[41]	92 ^[42]	90 ^[43]	89 ^[44]	278 ^[45]
Units: Liters
arithmetic mean (standard deviation)
Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238	0.008 ± 0.2729	0.100 ± 0.2511	-0.021 ± 0.2657	-0.013 ± 0.2509	0.053 ± 0.2958	0.041 ± 0.2738	0.023 ± 0.2561
Day 14, Post, n=248, 20, 86, 83, 77, 78, 241	0.034 ± 0.2707	0.075 ± 0.2425	0.010 ± 0.2168	-0.050 ± 0.2477	0.054 ± 0.2983	0.073 ± 0.2655	0.044 ± 0.2216
Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232	0.017 ± 0.2585	0.081 ± 0.2661	-0.034 ± 0.2875	-0.010 ± 0.2333	0.064 ± 0.2592	0.016 ± 0.2713	0.020 ± 0.2512
Day 28, Post, n=245, 19, 83, 81, 76, 72, 232	0.036 ± 0.2647	0.059 ± 0.2575	0.004 ± 0.2183	-0.034 ± 0.2401	0.049 ± 0.2639	0.027 ± 0.2369	0.029 ± 0.2307
Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224	0.005 ± 0.2295	-0.006 ± 0.2636	-0.024 ± 0.3210	0.011 ± 0.2415	0.022 ± 0.2522	-0.004 ± 0.2233	-0.001 ± 0.2858
Day 56, Post, n=237, 19, 78, 77, 74, 69, 224	0.020 ± 0.2614	-0.002 ± 0.2252	-0.012 ± 0.2524	0.004 ± 0.2373	0.026 ± 0.2556	-0.011 ± 0.2260	0.011 ± 0.2470
Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212	0.000 ± 0.2566	0.003 ± 0.2232	-0.049 ± 0.2549	0.005 ± 0.2668	0.015 ± 0.2739	0.007 ± 0.2461	0.010 ± 0.2829
Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22	0.071 ± 0.1586	0.168 ± 0.2652	0.108 ± 0.3888	0.056 ± 0.1782	0.052 ± 0.3481	0.162 ± 0.1426	0.075 ± 0.1974
Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6	0.134 ± 0.1514	0.153 ± 0.0933	0.083 ± 99999	-0.076 ± 99999	0.094 ± 99999	88888 ± 99999	-0.006 ± 0.1079

Notes
[39] - MITT Population.
[40] - MITT Population.
[41] - MITT Population.
[42] - MITT Population.
[43] - MITT Population.
[44] - MITT Population.
[45] - MITT Population.

No statistical analyses for this end point

Secondary: Change from hospital discharge in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Top of page

End point title

Change from hospital discharge in Clinic Visit trough FEV1 measured pre and post-bronchodilator

End point description

FEV1, defined as maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after administration with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre- and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre- and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1. Only those participants with data at specified data points were analyzed (represented by n= X in category titles). 99999 indicates standard deviation could not be calculated as single participant was analyzed. 88888 indicates number of participants analyzed was 0.

End point type

Secondary

End point timeframe

Baseline and pre- and post-bronchodilator on Days 14, 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[46]	22 ^[47]	91 ^[48]	92 ^[49]	90 ^[50]	89 ^[51]	278 ^[52]
Units: Liters
arithmetic mean (standard deviation)
Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20	0.082 ± 0.2783	0.355 ± 0.4207	0.069 ± 0.3012	-0.049 ± 0.1882	-0.069 ± 0.4905	0.173 ± 0.5137	0.002 ± 0.2343
Day 14, Post, n=5, 2, 1, 1, 1, 0, 5	0.056 ± 0.3372	0.431 ± 0.5190	0.119 ± 99999	0.310 ± 99999	-0.305 ± 99999	88888 ± 99999	-0.021 ± 0.1326
Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37	0.026 ± 0.2691	0.261 ± 0.5204	0.012 ± 0.2910	-0.085 ± 0.2072	0.012 ± 0.4020	0.030 ± 0.4029	-0.046 ± 0.2639
Day 28, Post, n=22, 2, 8, 1, 4, 4, 22	0.034 ± 0.2779	0.334 ± 0.5614	0.130 ± 0.2327	0.130 ± 99999	0.009 ± 0.2006	0.007 ± 0.3237	-0.094 ± 0.2293
Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36	0.019 ± 0.2282	0.106 ± 0.6138	0.019 ± 0.3509	0.014 ± 0.1938	-0.074 ± 0.3847	-0.042 ± 0.1840	-0.054 ± 0.2942
Day 56, Post, n=22, 2, 7, 1, 4, 5, 21	-0.014 ± 0.2896	0.139 ± 0.6838	0.042 ± 0.3068	0.098 ± 99999	-0.056 ± 0.3572	-0.072 ± 0.1490	-0.135 ± 0.2410
Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35	0.007 ± 0.2741	-0.027 ± 0.4554	0.121 ± 0.2770	-0.081 ± 0.1738	-0.072 ± 0.4391	0.043 ± 0.2511	-0.062 ± 0.2816
Day 84, Post, n=22, 2, 6, 1, 4, 5, 22	-0.039 ± 0.2610	0.133 ± 0.5162	0.037 ± 0.3341	0.108 ± 99999	0.021 ± 0.3151	0.006 ± 0.2180	-0.106 ± 0.2956

Notes
[46] - MITT Population.
[47] - MITT Population.
[48] - MITT Population.
[49] - MITT Population.
[50] - MITT Population.
[51] - MITT Population.
[52] - MITT Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving the exacerbations of chronic pulmonary disease tool (EXACT) definition of recovery from the index exacerbation

Top of page

End point title

Percentage of participants achieving the exacerbations of chronic pulmonary disease tool (EXACT) definition of recovery from the index exacerbation

End point description

EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score >=9 points from maximum observed value, sustained for >=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender.

End point type

Secondary

End point timeframe

Days 14, 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[53]	22 ^[54]	91 ^[55]	92 ^[56]	90 ^[57]	89 ^[58]	278 ^[59]
Units: Percentage of participants
Day 14	29	27	37	29	28	24	32
Day 28	40	41	52	43	42	27	42
Day 56	49	45	59	52	50	31	50
Day 84	51	50	59	54	50	37	54

Notes
[53] - MITT Population.
[54] - MITT Population.
[55] - MITT Population.
[56] - MITT Population.
[57] - MITT Population.
[58] - MITT Population.
[59] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[60]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

2.3

Notes
[60] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[61]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

2.17

Notes
[61] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[62]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.61

Notes
[62] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.49

Notes
[63] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[64]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.25

Notes
[64] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[65]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.63

Notes
[65] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 14 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 7

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[66]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

2.69

Notes
[66] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 8

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[67]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

2.33

Notes
[67] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 9

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[68]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.79

Notes
[68] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 10

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.74

Notes
[69] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 11

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

0.88

Notes
[70] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 12

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[71]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.49

Notes
[71] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 13

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[72]

Method

Parameter type

Posterior median odds ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

2.17

Notes
[72] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 14

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[73]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.27

Notes
[73] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 15

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[74]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.78

Notes
[74] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 16

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[75]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.67

Notes
[75] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 17

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[76]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.77

Notes
[76] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 18

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[77]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.42

Notes
[77] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 19

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[78]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

2.38

Notes
[78] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 20

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[79]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

Notes
[79] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 21

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[80]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.71

Notes
[80] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 22

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[81]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.48

Notes
[81] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 23

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[82]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

0.87

Notes
[82] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 24

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[83]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.47

Notes
[83] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Secondary: Time to recovery from index exacerbation using EXACT- PRO tool

Top of page

End point title

Time to recovery from index exacerbation using EXACT- PRO tool

End point description

Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score >=9 points from the Maximum Observed Value, sustained for >=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented.

End point type

Secondary

End point timeframe

From randomization to Week 12

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[84]	22 ^[85]	91 ^[86]	92 ^[87]	90 ^[88]	89 ^[89]	278 ^[90]
Units: Participants	141	11	54	50	45	34	149

Notes
[84] - MITT Population.
[85] - MITT Population.
[86] - MITT Population.
[87] - MITT Population.
[88] - MITT Population.
[89] - MITT Population.
[90] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[91]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.053

Confidence interval

level

95%

sides

2-sided

lower limit

0.477

upper limit

1.765

Notes
[91] - Treatment comparison between placebo and Nemiralisib 12.5 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[92]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.597

Notes
[92] - Treatment comparison between placebo and Nemiralisib 50 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[93]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.734

upper limit

1.432

Notes
[93] - Treatment comparison between placebo and Nemiralisib 100 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[94]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.719

upper limit

1.413

Notes
[94] - Treatment comparison between placebo and Nemiralisib 250 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[95]

Method

Parameter type

Posterior median hazard ratio

Point estimate

0.751

Confidence interval

level

95%

sides

2-sided

lower limit

0.487

upper limit

1.057

Notes
[95] - Treatment comparison between placebo and Nemiralisib 500 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[96]

Method

Parameter type

Posterior median hazard ratio

Point estimate

1.149

Confidence interval

level

95%

sides

2-sided

lower limit

0.899

upper limit

1.426

Notes
[96] - Treatment comparison between placebo and Nemiralisib 750 mcg was performed and posterior median hazard ratio and 95% HPD CrI has been presented.

Secondary: Mean severity of subsequent health care resource use (HCRU) exacerbations defined by EXACT

Top of page

End point title

Mean severity of subsequent health care resource use (HCRU) exacerbations defined by EXACT

End point description

Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation. Only those participants with data available at specified data points were analyzed (represented by n=X in the category title). 99999 indicates standard deviation could not be calculated as only one participant was analyzed.

End point type

Secondary

End point timeframe

Up to Week 12

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[97]	22 ^[98]	91 ^[99]	92 ^[100]	90 ^[101]	89 ^[102]	278 ^[103]
Units: Scores on a scale
arithmetic mean (standard deviation)
Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78	53.3 ± 12.16	64.6 ± 25.20	59.8 ± 12.82	50.5 ± 10.76	47.5 ± 13.95	57.6 ± 10.30	51.9 ± 10.78
Moderate, n=55, 3, 15, 23, 17, 10, 63	53.1 ± 11.54	60.0 ± 26.56	57.4 ± 11.08	50.0 ± 11.15	46.3 ± 14.20	53.8 ± 9.28	50.0 ± 10.17
Severe, n=13, 1, 9, 3, 10, 6, 20	54.0 ± 15.53	83.0 ± 99999	64.0 ± 15.01	55.3 ± 5.69	49.5 ± 13.95	64.1 ± 8.99	58.8 ± 10.34

Notes
[97] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[98] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[99] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[100] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[101] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[102] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.
[103] - Severity was derived for participants from MITT Population who had reported subsequent exacerbation.

No statistical analyses for this end point

Secondary: Percentage of responders using the COPD Assessment Test (CAT) on treatment Days 28, 56, and 84, and following EXACT defined recovery from the index exacerbation

Top of page

End point title

Percentage of responders using the COPD Assessment Test (CAT) on treatment Days 28, 56, and 84, and following EXACT defined recovery from the index exacerbation

End point description

The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score >=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score >=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.

End point type

Secondary

End point timeframe

Days 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[104]	22 ^[105]	91 ^[106]	92 ^[107]	90 ^[108]	89 ^[109]	278 ^[110]
Units: Percentage of responders
Day 28	32	36	34	39	38	34	25
Day 56	63	50	73	61	69	55	61
Day 84	70	55	78	65	72	60	66

Notes
[104] - MITT Population.
[105] - MITT Population.
[106] - MITT Population.
[107] - MITT Population.
[108] - MITT Population.
[109] - MITT Population.
[110] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[111]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

2.7

Notes
[111] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[112]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.77

Notes
[112] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[113]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

2.17

Notes
[113] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[114]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

Notes
[114] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[115]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.75

Notes
[115] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Anallysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[116]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

0.99

Notes
[116] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 28 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 7

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[117]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

1.41

Notes
[117] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 8

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[118]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.46

Notes
[118] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 9

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[119]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.48

Notes
[119] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 10

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[120]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

2.16

Notes
[120] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 11

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[121]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.17

Notes
[121] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 12

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[122]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.27

Notes
[122] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 56 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 13

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[123]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

1.2

Notes
[123] - Treatment comparison between placebo and nemiralisib 12.5 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 14

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[124]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

2.56

Notes
[124] - Treatment comparison between placebo and nemiralisib 50 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 15

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[125]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

1.3

Notes
[125] - Treatment comparison between placebo and nemiralisib 100 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 16

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[126]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.86

Notes
[126] - Treatment comparison between placebo and nemiralisib 250 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Statistical Analysis 17

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[127]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

1.02

Notes
[127] - Treatment comparison between placebo and nemiralisib 500 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented

Statistical Analysis 18

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[128]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.17

Notes
[128] - Treatment comparison between placebo and nemiralisib 750 mcg at Day 84 was performed and posterior median odds ratio and 95% HPD CrI has been presented.

Secondary: Change from Baseline in CAT total score

Top of page

End point title

Change from Baseline in CAT total score

End point description

CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). Total CAT score was calculated by summing scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented. Only those participants with data available at specified data points were analyzed (represented by n= X in category titles).

End point type

Secondary

End point timeframe

Baseline and at Days 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[129]	22 ^[130]	91 ^[131]	92 ^[132]	90 ^[133]	89 ^[134]	278 ^[135]
Units: Scores on a scale
median (confidence interval 95%)
Day 28, n=234, 19, 86, 80, 77, 74, 229	-4.7 (-5.6 to -3.8)	-2.3 (-5.1 to 0.5)	-4.0 (-5.4 to -2.7)	-3.9 (-5.4 to -2.4)	-5.1 (-6.5 to -3.7)	-3.1 (-4.5 to -1.6)	-4.7 (-5.6 to -3.8)
Day 56, n=231, 20, 78, 77, 76, 69, 222	-4.2 (-5.2 to -3.3)	-1.9 (-4.7 to 1.0)	-3.4 (-5.0 to -1.9)	-4.5 (-6.0 to -2.9)	-4.8 (-6.4 to -3.4)	-3.8 (-5.5 to -2.3)	-4.4 (-5.4 to -3.5)
Day 84, n=218, 17, 75, 75, 69, 62, 213	-4.6 (-5.6 to -3.6)	-2.7 (-6.0 to 0.3)	-3.5 (-5.0 to -1.9)	-5.1 (-6.7 to -3.5)	-4.7 (-6.3 to -3.1)	-3.8 (-5.4 to -2.1)	-4.2 (-5.2 to -3.2)

Notes
[129] - MITT Population.
[130] - MITT Population.
[131] - MITT Population.
[132] - MITT Population.
[133] - MITT Population.
[134] - MITT Population.
[135] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[136]

Method

Parameter type

Posterior adjusted median difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

5.2

Notes
[136] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[137]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

2.3

Notes
[137] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[138]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

2.4

Notes
[138] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[139]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

1.2

Notes
[139] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[140]

Method

Parameter type

Posterior adjacent median difference

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.3

Notes
[140] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[141]

Method

Parameter type

Posterior adjusted median difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Notes
[141] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 7

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[142]

Method

Parameter type

Posterior adjusted median difference

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

5.4

Notes
[142] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 8

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[143]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

2.4

Notes
[143] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 9

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[144]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.4

Notes
[144] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 10

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[145]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Notes
[145] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 11

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[146]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

2.2

Notes
[146] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analyis 12

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[147]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Notes
[147] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 13

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[148]

Method

Parameter type

Posterior adjusted median difference

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

5.1

Notes
[148] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 14

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[149]

Method

Parameter type

Posterior adjusted median difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

2.8

Notes
[149] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 15

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[150]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

1.1

Notes
[150] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 84 was performed and posterior adjsted median difference and 95% HPD CrI has been presented.

Statistical Analysis 16

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[151]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.7

Notes
[151] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 17

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[152]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

2.8

Notes
[152] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 18

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[153]

Method

Parameter type

Posterior adjusted median difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.7

Notes
[153] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Secondary: Percentage of responders on the St. George’s Respiratory Questionnaire (SGRQ) total score as measured by the SGRQ for COPD participants (SGRQ-C) at Days 28, 56, and 84

Top of page

End point title

Percentage of responders on the St. George’s Respiratory Questionnaire (SGRQ) total score as measured by the SGRQ for COPD participants (SGRQ-C) at Days 28, 56, and 84

End point description

SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score >=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score >=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Days 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[154]	22 ^[155]	91 ^[156]	92 ^[157]	90 ^[158]	89 ^[159]	278 ^[160]
Units: Percentage of responders
Day 28	21	14	19	26	32	24	21
Day 56	50	36	56	55	60	49	53
Day 84	61	50	66	63	68	57	62

Notes
[154] - MITT Population.
[155] - MITT Population.
[156] - MITT Population.
[157] - MITT Population.
[158] - MITT Population.
[159] - MITT Population.
[160] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[161]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

1.41

Notes
[161] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[162]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.47

Notes
[162] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[163]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

2.24

Notes
[163] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[164]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.91

Notes
[164] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[165]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

2.08

Notes
[165] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[166]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.4

Notes
[166] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 7

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[167]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

1.16

Notes
[167] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 8

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[168]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.98

Notes
[168] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 9

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[169]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.97

Notes
[169] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 10

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[170]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

2.27

Notes
[170] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 11

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[171]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.62

Notes
[171] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 12

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[172]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.5

Notes
[172] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 13

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[173]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

1.39

Notes
[173] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 14

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[174]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

2.01

Notes
[174] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 15

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[175]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.79

Notes
[175] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 84 was performed and posterior adjsted median difference and 95% HPD CrI has been presented.

Statistical Analysis 16

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[176]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

2.14

Notes
[176] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 17

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[177]

Method

Parameter type

Posterior median odds ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.45

Notes
[177] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 18

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[178]

Method

Parameter type

Posterior median odds ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.43

Notes
[178] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Secondary: Change from Baseline in SGRQ total score at Days 28, 56 and 84

Top of page

End point title

Change from Baseline in SGRQ total score at Days 28, 56 and 84

End point description

SGRQ-C is 40-item questionnaire was scored equivalent to SGRQ Total Score, ranging from 0-100, higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100*summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented. Only those participants with data at specified data points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline and Days 28, 56 and 84

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[179]	22 ^[180]	91 ^[181]	92 ^[182]	90 ^[183]	89 ^[184]	278 ^[185]
Units: Scores on a scale
median (confidence interval 95%)
Day 28, n=232, 19, 86, 78, 77, 72, 225	-7.7 (-9.8 to -5.7)	-5.7 (-12.2 to 0.5)	-8.2 (-11.4 to -5.1)	-10.6 (-13.8 to -7.1)	-10.9 (-14.2 to -7.6)	-7.8 (-11.2 to -4.3)	-7.9 (-9.9 to -5.9)
Day 56, n=227, 20, 78, 77, 74, 68, 219	-8.0 (-10.2 to -6.0)	-3.9 (-10.4 to 2.8)	-9.3 (-12.5 to -5.9)	-10.7 (-14.1 to -7.3)	-11.3 (-14.6 to -7.6)	-8.9 (-12.6 to -5.5)	-8.4 (-10.6 to -6.3)
Day 84, n=218, 17, 74, 74, 69, 60, 209	-9.1 (-11.3 to -6.8)	-6.6 (-13.6 to 0.3)	-9.3 (-12.8 to -6.0)	-11.3 (-14.8 to -7.7)	-10.9 (-14.4 to -7.2)	-9.4 (-13.1 to -5.5)	-7.9 (-10.1 to -5.7)

Notes
[179] - MITT Population.
[180] - MITT Population.
[181] - MITT Population.
[182] - MITT Population.
[183] - MITT Population.
[184] - MITT Population.
[185] - MITT Population.

Statistical Analysis 1

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[186]

Method

Parameter type

Posterior adjusted median difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

8.3

Notes
[186] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 2

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[187]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

3.1

Notes
[187] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 3

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[188]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

1.1

Notes
[188] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 4

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[189]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

0.4

Notes
[189] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 5

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[190]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

3.5

Notes
[190] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 7

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[191]

Method

Parameter type

Posterior adjusted median difference

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

Notes
[191] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analyais 6

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[192]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

2.3

Notes
[192] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 28 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 8

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[193]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

2.5

Notes
[193] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 9

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[194]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

1.1

Notes
[194] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 10

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[195]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.3

upper limit

0.4

Notes
[195] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 11

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[196]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

Notes
[196] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 12

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[197]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

2.5

Notes
[197] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 56 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 13

Comparison groups

Placebo v Nemiralisib 12.5 mcg

Number of subjects included in analysis

298

Analysis specification

Pre-specified

Analysis type

other ^[198]

Method

Parameter type

Posterior adjusted median difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

9.4

Notes
[198] - Treatment comparison between placebo and Nemiralisib 12.5 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 14

Comparison groups

Placebo v Nemiralisib 50 mcg

Number of subjects included in analysis

367

Analysis specification

Pre-specified

Analysis type

other ^[199]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

3.6

Notes
[199] - Treatment comparison between placebo and Nemiralisib 50 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 15

Comparison groups

Placebo v Nemiralisib 100 mcg

Number of subjects included in analysis

368

Analysis specification

Pre-specified

Analysis type

other ^[200]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

1.8

Notes
[200] - Treatment comparison between placebo and Nemiralisib 100 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 16

Comparison groups

Placebo v Nemiralisib 250 mcg

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

other ^[201]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

2.3

Notes
[201] - Treatment comparison between placebo and Nemiralisib 250 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 17

Comparison groups

Placebo v Nemiralisib 500 mcg

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

other ^[202]

Method

Parameter type

Posterior adjusted median difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

3.8

Notes
[202] - Treatment comparison between placebo and Nemiralisib 500 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Statistical Analysis 18

Comparison groups

Placebo v Nemiralisib 750 mcg

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

other ^[203]

Method

Parameter type

Posterior adjusted median difference

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

Notes
[203] - Treatment comparison between placebo and Nemiralisib 750 mcg at Day 84 was performed and posterior adjusted median difference and 95% HPD CrI has been presented.

Secondary: Mean number of occasions of rescue medication use per day

Top of page

End point title

Mean number of occasions of rescue medication use per day

End point description

Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[204]	22 ^[205]	91 ^[206]	92 ^[207]	90 ^[208]	89 ^[209]	278 ^[210]
Units: No. of occasions of rescue use per day
arithmetic mean (standard deviation)
Week 1, n=254, 21, 87, 88, 80, 79, 254	1.699 ± 1.7674	2.112 ± 2.2977	1.633 ± 1.4320	1.926 ± 2.1569	1.670 ± 1.5728	1.917 ± 1.9298	1.747 ± 1.7332
Week 2, n=259, 21, 88, 89, 80, 82, 252	1.650 ± 1.8711	2.231 ± 2.7169	1.469 ± 1.4036	1.712 ± 2.0310	1.497 ± 1.5700	1.611 ± 1.7717	1.587 ± 1.6531
Week 3, n=256, 21, 90, 88, 80, 81, 245	1.729 ± 1.8157	2.021 ± 2.2926	1.495 ± 1.3943	1.693 ± 1.9679	1.488 ± 1.6611	1.742 ± 1.8380	1.655 ± 1.7430
Week 4, n=250, 21, 89, 87, 81, 77, 243	1.684 ± 1.7706	2.190 ± 2.3657	1.514 ± 1.5022	1.720 ± 2.0083	1.489 ± 1.6734	2.009 ± 2.0506	1.707 ± 1.7512
Week 5, n=251, 20, 88, 85, 78, 76, 240	1.735 ± 1.8662	2.329 ± 2.6394	1.533 ± 1.5706	1.750 ± 2.0380	1.535 ± 1.8384	1.949 ± 1.9685	1.737 ± 1.8030
Week 6, n=250, 20, 86, 84, 78, 72, 234	1.741 ± 1.9543	2.378 ± 2.6904	1.382 ± 1.4000	1.792 ± 2.0822	1.636 ± 1.8042	1.936 ± 2.0729	1.780 ± 1.8083
Week 7, n=250, 20, 85, 83, 77, 71, 231	1.703 ± 1.9914	2.479 ± 2.6976	1.531 ± 1.6374	1.697 ± 2.0769	1.628 ± 1.8741	1.899 ± 2.1694	1.826 ± 1.8778
Week 8, n=250, 20, 84, 83, 77, 71, 231	1.656 ± 1.8606	2.736 ± 3.1579	1.553 ± 1.5884	1.616 ± 1.9444	1.572 ± 1.8294	2.006 ± 2.2242	1.824 ± 1.8397
Week 9, n=244, 20, 82, 81, 76, 71, 229	1.708 ± 1.8709	2.765 ± 3.1104	1.608 ± 1.7699	1.658 ± 2.0646	1.720 ± 1.8918	1.953 ± 2.1838	1.775 ± 1.8753
Week 10, n=241, 20, 81, 80, 73, 71, 227	1.698 ± 1.9023	2.543 ± 2.8753	1.589 ± 1.6571	1.596 ± 1.9809	1.546 ± 1.8824	1.927 ± 2.1613	1.705 ± 1.7646
Week 11, n=241, 20, 79, 80, 73, 71, 226	1.729 ± 1.9406	2.164 ± 2.2504	1.404 ± 1.4897	1.602 ± 1.9435	1.672 ± 1.9447	1.926 ± 2.3243	1.716 ± 1.7421
Week 12, n=240, 20, 78, 80, 73, 70, 225	1.666 ± 1.7913	2.386 ± 2.8157	1.414 ± 1.3920	1.671 ± 1.9612	1.712 ± 1.9532	1.790 ± 2.1140	1.731 ± 1.7245
Over 12 Week, n=273, 21, 91, 91, 86, 83, 268	1.684 ± 1.6903	2.330 ± 2.4715	1.553 ± 1.4044	1.750 ± 1.9048	1.620 ± 1.5994	1.921 ± 1.9201	1.733 ± 1.6618

Notes
[204] - MITT Population.
[205] - MITT Population.
[206] - MITT Population.
[207] - MITT Population.
[208] - MITT Population.
[209] - MITT Population.
[210] - MITT Population.

No statistical analyses for this end point

Secondary: Percentage of rescue-free days

Top of page

End point title

Percentage of rescue-free days

End point description

Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[211]	22 ^[212]	91 ^[213]	92 ^[214]	90 ^[215]	89 ^[216]	278 ^[217]
Units: Percentage of rescue free days
arithmetic mean (standard deviation)
Week 1, n=254, 21, 87, 88, 80, 79, 254	34.898 ± 37.7118	36.076 ± 44.3182	29.849 ± 38.3385	33.392 ± 39.7372	32.583 ± 38.3577	34.453 ± 35.9802	29.779 ± 36.1498
Week 2, n=259, 21, 88, 89, 80, 82, 252	41.002 ± 40.9566	40.819 ± 46.7899	32.145 ± 41.2227	43.017 ± 43.9884	38.573 ± 40.3629	40.595 ± 41.1717	33.639 ± 38.9767
Week 3, n=256, 21, 90, 88, 80, 81, 245	38.204 ± 39.0621	38.776 ± 44.0612	31.643 ± 38.0943	39.964 ± 40.3936	41.191 ± 42.1751	34.923 ± 40.4026	33.006 ± 38.4986
Week 4, n=250, 21, 89, 87, 81, 77, 243	39.678 ± 40.8359	35.376 ± 43.9405	32.531 ± 39.0078	42.202 ± 43.0692	43.194 ± 41.0201	30.986 ± 38.5941	32.394 ± 39.0174
Week 5, n=251, 20, 88, 85, 78, 76, 240	38.262 ± 40.7807	35.005 ± 41.8344	35.552 ± 40.5745	41.682 ± 41.3648	41.026 ± 42.1584	33.912 ± 37.9973	33.168 ± 39.0654
Week 6, n=250, 20, 86, 84, 78, 72, 234	40.287 ± 42.2167	37.870 ± 40.2125	35.384 ± 40.9175	41.720 ± 44.0117	39.196 ± 41.6575	35.519 ± 42.2122	32.351 ± 39.2542
Week 7, n=250, 20, 85, 83, 77, 71, 231	41.373 ± 43.4266	32.145 ± 43.1992	35.634 ± 41.3319	45.266 ± 43.5910	40.409 ± 42.0560	38.232 ± 41.0296	31.975 ± 39.4910
Week 8, n=250, 20, 84, 83, 77, 71, 231	42.058 ± 41.2168	34.290 ± 42.8300	33.029 ± 41.0867	44.118 ± 41.6682	42.918 ± 42.8354	34.811 ± 39.3585	32.357 ± 39.9221
Week 9, n=244, 20, 82, 81, 76, 71, 229	39.268 ± 40.5300	32.145 ± 44.6657	32.759 ± 39.2972	42.505 ± 41.2121	39.476 ± 42.2376	36.823 ± 42.3513	33.606 ± 39.4690
Week 10, n=241, 20, 81, 80, 73, 71, 227	40.608 ± 41.0492	35.000 ± 42.3430	32.456 ± 40.7192	43.396 ± 42.3040	41.492 ± 42.1984	37.024 ± 41.2291	33.483 ± 40.1924
Week 11, n=241, 20, 79, 80, 73, 71, 226	39.701 ± 41.9689	38.575 ± 44.2366	35.624 ± 42.6625	42.859 ± 41.7845	39.337 ± 42.3061	39.841 ± 43.7237	33.127 ± 39.1842
Week 12, n=240, 20, 78, 80, 73, 70, 225	41.390 ± 40.8871	39.415 ± 45.0442	37.369 ± 40.2613	41.300 ± 39.8199	39.981 ± 40.8296	42.236 ± 42.1567	33.906 ± 38.4851
Over 12 Week, n=273, 21, 91, 91, 86, 83, 268	39.743 ± 36.8957	35.533 ± 39.0694	33.590 ± 36.6456	40.441 ± 37.6285	39.631 ± 36.5157	35.820 ± 34.6377	32.743 ± 33.9362

Notes
[211] - MITT Population.
[212] - MITT Population.
[213] - MITT Population.
[214] - MITT Population.
[215] - MITT Population.
[216] - MITT Population.
[217] - MITT Population.

No statistical analyses for this end point

Secondary: Plasma concentration of Nemiralisib

Top of page

End point title

Plasma concentration of Nemiralisib ^[218]

End point description

Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable [NQ] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[218] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[219]	22 ^[220]	24 ^[221]	19 ^[222]	20 ^[223]	73 ^[224]
Units: Picograms per milliliter
geometric mean (geometric coefficient of variation)
Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69	113.6 ± 6	62.0 ± 46	142.8 ± 44	416.0 ± 59	687.3 ± 53	1069.6 ± 70
Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67	54.9 ± 43	109.9 ± 51	253.7 ± 73	767.6 ± 71	1492.0 ± 59	1972.0 ± 110
Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65	35.0 ± 57	93.1 ± 58	231.8 ± 53	657.0 ± 61	1146.7 ± 56	1622.7 ± 90
Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67	23.6 ± 24	60.5 ± 45	129.4 ± 46	315.6 ± 85	528.3 ± 110	937.6 ± 101
Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63	36.2 ± 26	104.9 ± 70	253.3 ± 52	807.0 ± 66	1552.2 ± 83	1717.6 ± 114
Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64	28.1 ± 15	85.4 ± 40	211.4 ± 41	598.8 ± 39	1079.5 ± 80	1388.1 ± 101

Notes
[219] - PK Population.
[220] - PK Population.
[221] - PK Population.
[222] - PK Population.
[223] - PK Population.
[224] - PK Population.

No statistical analyses for this end point

Secondary: Area under the concentration time curve (AUC) from time zero to 24 hours [AUC(0-24)] of nemiralisib

Top of page

End point title

Area under the concentration time curve (AUC) from time zero to 24 hours [AUC(0-24)] of nemiralisib ^[225]

End point description

Plasma samples were collected at indicated time points and analyzed. 99999 indicates sparse plasma concentrations of GSK2269557 were summarized in all PK evaluable participants by time interval as stated in protocol. No subsequent population PK was conducted on these plasma data to derive PK parameters due to termination of the development of project at the end of the study. The plasma exposure summarized from all the evaluated participants over the interval of collection of these sparse samples provides adequate information on the adequacy of the doses the participants were exposed in this study.

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[225] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[226]	22 ^[227]	24 ^[228]	19 ^[229]	20 ^[230]	73 ^[231]
Units: Hours*picograms per milliliter
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[226] - PK Population.
[227] - PK Population.
[228] - PK Population.
[229] - PK Population.
[230] - PK Population.
[231] - PK Population.

No statistical analyses for this end point

Secondary: AUC from time zero to time 't' [AUC(0-t)] of nemiralisib

Top of page

End point title

AUC from time zero to time 't' [AUC(0-t)] of nemiralisib ^[232]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[232] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[233]	22 ^[234]	24 ^[235]	19 ^[236]	20 ^[237]	73 ^[238]
Units: Hours*picograms per milliliter
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[233] - PK Population.
[234] - PK Population.
[235] - PK Population.
[236] - PK Population.
[237] - PK Population.
[238] - PK Population.

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Drug Concentration (Cmax) of nemiralisib

Top of page

End point title

Maximum Observed Plasma Drug Concentration (Cmax) of nemiralisib ^[239]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[239] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[240]	22 ^[241]	24 ^[242]	19 ^[243]	20 ^[244]	73 ^[245]
Units: Picograms per milliliter
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[240] - PK Population.
[241] - PK Population.
[242] - PK Population.
[243] - PK Population.
[244] - PK Population.
[245] - PK Population.

No statistical analyses for this end point

Secondary: Time to reach Cmax (Tmax) of nemiralisib

Top of page

End point title

Time to reach Cmax (Tmax) of nemiralisib ^[246]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[246] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[247]	22 ^[248]	24 ^[249]	19 ^[250]	20 ^[251]	73 ^[252]
Units: Hours
median (full range (min-max))	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[247] - PK Population.
[248] - PK Population.
[249] - PK Population.
[250] - PK Population.
[251] - PK Population.
[252] - PK Population.

No statistical analyses for this end point

Secondary: Plasma drug concentration at pre-dose (Ctrough) of nemiralisib

Top of page

End point title

Plasma drug concentration at pre-dose (Ctrough) of nemiralisib ^[253]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28

Notes
[253] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Plasma concentration was analyzed for the active comparator, Nemiralisib.

End point values	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	5 ^[254]	22 ^[255]	24 ^[256]	19 ^[257]	20 ^[258]	73 ^[259]
Units: Picograms per milliliter
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[254] - PK Population.
[255] - PK Population.
[256] - PK Population.
[257] - PK Population.
[258] - PK Population.
[259] - PK Population.

No statistical analyses for this end point

Secondary: Number of participants reporting non-serious adverse events (non-SAEs), SAEs and AE of special interest (AESI)

Top of page

End point title

Number of participants reporting non-serious adverse events (non-SAEs), SAEs and AE of special interest (AESI)

End point description

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received.

End point type

Secondary

End point timeframe

Up to Week 24

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[260]	22 ^[261]	91 ^[262]	92 ^[263]	90 ^[264]	89 ^[265]	278 ^[266]
Units: Participants
Any non-SAE	31	1	14	19	25	36	101
Any SAE	23	2	9	13	16	6	26
Any AESI	9	0	10	10	21	29	93

Notes
[260] - Safety Population.
[261] - Safety Population.
[262] - Safety Population.
[263] - Safety Population.
[264] - Safety Population.
[265] - Safety Population.
[266] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with worst case post Baseline diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate

Top of page

End point title

Number of participants with worst case post Baseline diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate

End point description

The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	271 ^[267]	21 ^[268]	91 ^[269]	92 ^[270]	88 ^[271]	88 ^[272]	266 ^[273]
Units: Participants
DBP, To low	8	3	3	0	4	4	7
DBP, To within range/no change	260	17	85	91	79	82	256
DBP, To high	3	1	3	1	5	2	3
Pulse rate, To low	1	0	0	0	0	0	0
Pulse rate,To within range/no change	265	21	84	90	82	83	258
Pulse rate, To high	5	0	7	2	6	5	8
SBP, To low	11	1	5	3	2	3	8
SBP, To withinn range/no change	250	18	83	82	79	80	239
SBP, To high	10	2	3	7	8	6	19

Notes
[267] - Safety Population.
[268] - Safety Population.
[269] - Safety Population.
[270] - Safety Population.
[271] - Safety Population.
[272] - Safety Population.
[273] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with abnormal electrocardiogram (ECG) findings

Top of page

End point title

Number of participants with abnormal electrocardiogram (ECG) findings

End point description

A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented.

End point type

Secondary

End point timeframe

Screening, Days 14, 84, 112 and at early withdrawal

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[274]	22 ^[275]	91 ^[276]	92 ^[277]	90 ^[278]	89 ^[279]	278 ^[280]
Units: Participants
Screening	93	10	25	37	28	21	86
Day 14	88	8	24	33	29	18	74
Day 84	79	8	22	27	24	18	64
Day 112	77	11	28	28	25	20	75
Early withdrawal	3	0	2	1	3	1	4

Notes
[274] - Safety Population.
[275] - Safety Population.
[276] - Safety Population.
[277] - Safety Population.
[278] - Safety Population.
[279] - Safety Population.
[280] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with worst case post Baseline clinical chemistry values

Top of page

End point title

Number of participants with worst case post Baseline clinical chemistry values

End point description

Blood samples were collected for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Upto Week 16

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[281]	22 ^[282]	91 ^[283]	92 ^[284]	90 ^[285]	89 ^[286]	278 ^[287]
Units: Participants
Alb,To low, n=266, 21, 91, 90, 87, 85, 263	2	0	0	0	1	1	2
Alb,w/in range/no change,n=266,21,91,90,87,85,263	264	21	90	90	85	84	261
Alb,To high,n=266,21,91,90,87,85,263	0	0	1	0	1	0	0
Cal,To low, n=266, 21, 90, 90, 87, 85, 263	1	0	0	0	0	1	1
Cal,w/in range/no change,n=266,21,90,90,87,85,263	265	21	90	90	87	84	262
Cal,To high, n=266,21,90,90,87,85,263	0	0	0	0	0	0	0
Crt,To low, n=266, 21, 91, 90, 87, 85, 263	27	3	10	7	4	9	32
Crt,w/in range/no change,n=266,21,91,90,87,85,263	237	18	81	82	80	76	231
Crt,To high, n=266,21,91,90,87,85,263	2	0	0	1	3	0	0
Glu,To low, n=266, 21, 91, 90, 87, 85, 263	0	0	0	1	0	0	0
Glu,w/in range/no change,n=266,21,91,90,87,85,263	266	21	91	89	87	85	263
Glu,To high, n=266,21,91,90,87,85,263	0	0	0	0	0	0	0
Pot,To low, n=266, 21, 90, 90, 87, 85, 263	0	0	0	0	0	0	0
Pot,w/in range/no change,n=266,21,90,90,87,85,263	264	21	90	90	86	84	262
Pot,To high, n=266,21,90,90,87,85,263	2	0	0	0	1	1	1
Sod,To low, n=266, 21, 91, 90, 87, 85, 263	0	0	0	0	0	0	0
Sod,w/in range/no change,n=266,21,91,90,87,85,263	266	21	91	90	87	85	263
Sod,To high, n=266,21,91,90,87,85,263	0	0	0	0	0	0	0
BUN,To low, n=266, 21, 91, 90, 87, 85, 263	7	0	3	2	2	3	6
BUN,w/in range/no change,n=266,21,91,90,87,85,263	256	21	88	86	85	82	253
BUN,To high, n=266,21,91,90,87,85,263	3	0	0	2	0	0	4

Notes
[281] - Safety Population.
[282] - Safety Population.
[283] - Safety Population.
[284] - Safety Population.
[285] - Safety Population.
[286] - Safety Population.
[287] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with worst case post Baseline hematology values

Top of page

End point title

Number of participants with worst case post Baseline hematology values

End point description

Blood samples were collected for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Upto Week 16

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[288]	22 ^[289]	91 ^[290]	92 ^[291]	90 ^[292]	89 ^[293]	278 ^[294]
Units: Participants
Hb,To low, n=260, 20, 90, 90, 84, 81, 254	0	0	0	0	0	0	0
Hb,w/in range/no change,n=260,20,90,90,84,81,254	260	20	90	90	84	81	253
Hb,To high,n=260, 20, 90, 90, 84, 81, 254	0	0	0	0	0	0	1
Leu,To low,n=259, 20, 90, 90, 83, 78, 251	0	0	0	0	0	0	0
Leu,w/in range/no change,n=259,20,90,90,83,78,251	211	16	81	74	63	62	201
Leu,To high, n=259,20,90,90,83,78,251	48	4	9	16	20	16	50
Lym,To low, n=256, 20, 85, 88, 82, 77, 249	8	1	6	7	7	2	11
Lym,w/in range/no change,n=256,20,85,88,82,77,249	239	19	79	76	70	73	226
Lym,To high,n=256,20,85,88,82,77,249	9	0	0	5	5	2	12
Neu, To low, n=256,20,85,88,82,77,249	3	0	1	1	0	0	2
Neu,w/in range/no change,n=256,20,85,88,82,77,249	215	17	73	76	68	60	213
Neu,To high, n=256,20,85,88,82,77,249	38	3	11	11	14	17	34
Pla,To low, n=253, 19, 88, 90, 84, 78, 245	0	0	0	0	0	0	0
Pla,w/in range/no change,n=253,19,88,90,84,78,245	253	19	88	90	84	78	245
Pla,To high, n=253,19,88,90,84,78,245	0	0	0	0	0	0	0

Notes
[288] - Safety Population.
[289] - Safety Population.
[290] - Safety Population.
[291] - Safety Population.
[292] - Safety Population.
[293] - Safety Population.
[294] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants reporting COPD exacerbations

Top of page

End point title

Number of participants reporting COPD exacerbations

End point description

Participants reporting acute COPD exacerbations during the study period has been presented.

End point type

Secondary

End point timeframe

Up to Week 16

End point values	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Number of subjects analysed	276 ^[295]	22 ^[296]	91 ^[297]	92 ^[298]	90 ^[299]	89 ^[300]	278 ^[301]
Units: Participants	8	1	6	4	4	3	17

Notes
[295] - Safety Population.
[296] - Safety Population.
[297] - Safety Population.
[298] - Safety Population.
[299] - Safety Population.
[300] - Safety Population.
[301] - Safety Population.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Non-serious AEs and SAEs were collected up to Week 24

Adverse event reporting additional description

Non-serious AEs and SAEs were summarized for the Safety Population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo

Reporting group description

Reporting group title

Nemiralisib 12.5 mcg

Reporting group description

Reporting group title

Nemiralisib 50 mcg

Reporting group description

Reporting group title

Nemiralisib 100 mcg

Reporting group description

Reporting group title

Nemiralisib 250 mcg

Reporting group description

Reporting group title

Nemiralisib 500 mcg

Reporting group description

Reporting group title

Nemiralisib 750 mcg

Reporting group description

Serious adverse events	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Total subjects affected by serious adverse events
subjects affected / exposed	23 / 276 (8.33%)	2 / 22 (9.09%)	9 / 91 (9.89%)	13 / 92 (14.13%)	16 / 90 (17.78%)	6 / 89 (6.74%)	26 / 278 (9.35%)
number of deaths (all causes)	1	0	3	1	0	0	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	1 / 91 (1.10%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine tumour
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Arterial thrombosis
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Swelling
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chroni obstructive pulmonary disease
subjects affected / exposed	8 / 276 (2.90%)	1 / 22 (4.55%)	6 / 91 (6.59%)	4 / 92 (4.35%)	4 / 90 (4.44%)	3 / 89 (3.37%)	17 / 278 (6.12%)
occurrences causally related to treatment / all	1 / 8	0 / 1	1 / 7	0 / 4	0 / 5	0 / 3	1 / 17
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wheezing
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Conversion disorder
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	1 / 89 (1.12%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	1 / 89 (1.12%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina unstable
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	2 / 90 (2.22%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	1 / 89 (1.12%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Sinus arrhythmia
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	1 / 89 (1.12%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Intracranial hematoma
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Enterocele
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	1 / 89 (1.12%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	1 / 91 (1.10%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bile duct stone
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	0 / 276 (0.00%)	1 / 22 (4.55%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	1 / 91 (1.10%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	4 / 276 (1.45%)	0 / 22 (0.00%)	1 / 91 (1.10%)	2 / 92 (2.17%)	3 / 90 (3.33%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 2	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	1 / 91 (1.10%)	1 / 92 (1.09%)	1 / 90 (1.11%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	1 / 92 (1.09%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis klebsiella
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	1 / 91 (1.10%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 276 (0.36%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 276 (0.00%)	1 / 22 (4.55%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	0 / 278 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 276 (0.00%)	0 / 22 (0.00%)	0 / 91 (0.00%)	0 / 92 (0.00%)	0 / 90 (0.00%)	0 / 89 (0.00%)	1 / 278 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Nemiralisib 12.5 mcg	Nemiralisib 50 mcg	Nemiralisib 100 mcg	Nemiralisib 250 mcg	Nemiralisib 500 mcg	Nemiralisib 750 mcg
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 276 (11.23%)	1 / 22 (4.55%)	14 / 91 (15.38%)	19 / 92 (20.65%)	25 / 90 (27.78%)	36 / 89 (40.45%)	101 / 278 (36.33%)
Nervous system disorders
Headache
subjects affected / exposed	23 / 276 (8.33%)	1 / 22 (4.55%)	6 / 91 (6.59%)	8 / 92 (8.70%)	4 / 90 (4.44%)	2 / 89 (2.25%)	15 / 278 (5.40%)
occurrences all number	41	1	8	10	5	2	18
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	13 / 276 (4.71%)	0 / 22 (0.00%)	10 / 91 (10.99%)	11 / 92 (11.96%)	23 / 90 (25.56%)	31 / 89 (34.83%)	96 / 278 (34.53%)
occurrences all number	13	0	12	17	27	58	141
Oropharyngeal pain
subjects affected / exposed	2 / 276 (0.72%)	0 / 22 (0.00%)	0 / 91 (0.00%)	2 / 92 (2.17%)	3 / 90 (3.33%)	5 / 89 (5.62%)	2 / 278 (0.72%)
occurrences all number	2	0	0	2	3	5	2

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

26 Sep 2017

Amendment 01: Updated and clarified the protocol during the Voluntary Harmonization Procedure in the European Union (EU).

14 Dec 2017

Amendment 02: Added the 12.5 mcg nemiralisib dose, added the provision for a 25 mcg dose to be added later, removed restrictions on theophylline use, made changes to discontinuation criteria, clarified the protocol, corrected minor discrepancies, and changed serious adverse events (SAE) recording such that SAEs prior to the start of study treatment were only collected if they were considered related to study participation or a GSK product.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in Clinic Visit trough forced expiratory volume in one second (FEV1) at Day 84 measured post bronchodilator

Primary: Change from Baseline in Clinic Visit trough forced expiratory volume in one second (FEV1) at Day 84 measured post bronchodilator

Secondary: Rate of moderate and severe exacerbations over 12-week treatment period

Secondary: Rate of moderate and severe exacerbations over 12-week treatment period

Secondary: Number of participants with Time to next moderate/severe exacerbation following index exacerbation

Secondary: Number of participants with Time to next moderate/severe exacerbation following index exacerbation

Secondary: Change from Baseline in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Secondary: Change from Baseline in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Secondary: Change from hospital discharge in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Secondary: Change from hospital discharge in Clinic Visit trough FEV1 measured pre and post-bronchodilator

Secondary: Percentage of participants achieving the exacerbations of chronic pulmonary disease tool (EXACT) definition of recovery from the index exacerbation

Secondary: Percentage of participants achieving the exacerbations of chronic pulmonary disease tool (EXACT) definition of recovery from the index exacerbation

Secondary: Time to recovery from index exacerbation using EXACT- PRO tool

Secondary: Time to recovery from index exacerbation using EXACT- PRO tool

Secondary: Mean severity of subsequent health care resource use (HCRU) exacerbations defined by EXACT

Secondary: Mean severity of subsequent health care resource use (HCRU) exacerbations defined by EXACT

Secondary: Percentage of responders using the COPD Assessment Test (CAT) on treatment Days 28, 56, and 84, and following EXACT defined recovery from the index exacerbation

Secondary: Percentage of responders using the COPD Assessment Test (CAT) on treatment Days 28, 56, and 84, and following EXACT defined recovery from the index exacerbation

Secondary: Change from Baseline in CAT total score

Secondary: Change from Baseline in CAT total score

Secondary: Percentage of responders on the St. George’s Respiratory Questionnaire (SGRQ) total score as measured by the SGRQ for COPD participants (SGRQ-C) at Days 28, 56, and 84

Secondary: Percentage of responders on the St. George’s Respiratory Questionnaire (SGRQ) total score as measured by the SGRQ for COPD participants (SGRQ-C) at Days 28, 56, and 84

Secondary: Change from Baseline in SGRQ total score at Days 28, 56 and 84

Secondary: Change from Baseline in SGRQ total score at Days 28, 56 and 84

Secondary: Mean number of occasions of rescue medication use per day

Secondary: Mean number of occasions of rescue medication use per day

Secondary: Percentage of rescue-free days

Secondary: Percentage of rescue-free days

Secondary: Plasma concentration of Nemiralisib

Secondary: Plasma concentration of Nemiralisib

Secondary: Area under the concentration time curve (AUC) from time zero to 24 hours [AUC(0-24)] of nemiralisib

Secondary: Area under the concentration time curve (AUC) from time zero to 24 hours [AUC(0-24)] of nemiralisib

Secondary: AUC from time zero to time 't' [AUC(0-t)] of nemiralisib

Secondary: AUC from time zero to time 't' [AUC(0-t)] of nemiralisib

Secondary: Maximum Observed Plasma Drug Concentration (Cmax) of nemiralisib

Secondary: Maximum Observed Plasma Drug Concentration (Cmax) of nemiralisib

Secondary: Time to reach Cmax (Tmax) of nemiralisib

Secondary: Time to reach Cmax (Tmax) of nemiralisib

Secondary: Plasma drug concentration at pre-dose (Ctrough) of nemiralisib

Secondary: Plasma drug concentration at pre-dose (Ctrough) of nemiralisib

Secondary: Number of participants reporting non-serious adverse events (non-SAEs), SAEs and AE of special interest (AESI)

Secondary: Number of participants reporting non-serious adverse events (non-SAEs), SAEs and AE of special interest (AESI)

Secondary: Number of participants with worst case post Baseline diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate

Secondary: Number of participants with worst case post Baseline diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate

Secondary: Number of participants with abnormal electrocardiogram (ECG) findings

Secondary: Number of participants with abnormal electrocardiogram (ECG) findings

Secondary: Number of participants with worst case post Baseline clinical chemistry values

Secondary: Number of participants with worst case post Baseline clinical chemistry values

Secondary: Number of participants with worst case post Baseline hematology values

Secondary: Number of participants with worst case post Baseline hematology values

Secondary: Number of participants reporting COPD exacerbations

Secondary: Number of participants reporting COPD exacerbations

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information