Clinical Study to Evaluate the Efficacy and Safety of VR506 Using a New Inhaler for the Treatment of Asthma

• Sponsor: Vectura Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01720069
• Collaborator: (none)
• Enrollment: 197
• Locations: 77
• Arms: 3
• Duration (Months): 12
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To evaluate the clinical efficacy, safety, tolerability and dose-response relationship, using oral corticosteroid (OCS) modulation, of 3 different doses of VR506 using a twice daily regimen from a new dry powder inhaler (nDPI) for 16 weeks in subjects with severe persistent asthma requiring OCS therapy, i.e. Step 5 treatment as defined by modified Global Initiative for Asthma (GINA) guidelines 2011.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: VR506	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised Double-blind, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of VR506 From a New Dry Powder Inhaler in Subjects With Severe Persistent Asthma Requiring Oral Corticosteroid Therapy.
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dose 1 VR506 VR506 inhalation powder delivered via a new dry powder inhaler device	Drug: VR506; VR506 inhalation powder delivered via a new dry powder inhaler device
Active Comparator: Dose 2 VR506 VR506 inhalation powder delivered via a new dry powder inhaler device	Drug: VR506; VR506 inhalation powder delivered via a new dry powder inhaler device
Active Comparator: Dose 3 VR506 VR506 inhalation powder delivered via a new dry powder inhaler device	Drug: VR506; VR506 inhalation powder delivered via a new dry powder inhaler device

Outcome Measures

Primary Outcome Measures

1. Mean Prednisone/Prednisolone Dose for Analysis (PDA) at End of Study (Week 16) [16 weeks]

   The mean asthma control prednisone/prednisolone dose at end of study (week 16)

Secondary Outcome Measures

1. Mean Change From Start of Treatment Baseline to End of Study (Week 16) for In-clinic Morning Pre-Dose Forced Expiratory Volume In 1 Second (FEV1) [Baseline and 16 weeks]

2. Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Asthma Control Questionnaire (ACQ-5) Mean Total Score [Baseline and 16 weeks]

   Change from baseline to end of study (week 16) in 5 item asthma control questionnaire (ACQ-5) mean total score (range 0 (better) to 6 (worse)). The mean total score is calculated as the mean for each subject at each visit of 5 questions, each scored from 0 (better) to 6 (worse).

3. Mean Change From Start of Treatment Baseline to End of Study (Week 16) for In-clinic Weekly Morning Pre-dose Peak Expiratory Flow (PEF) [Baseline and 16 weeks]

4. Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Weekly Average Asthma Night-time Symptom Score [Baseline and 16 weeks]

   To measure the change from baseline to end of study for the weekly mean asthma night time symptom score, scored from 0 (not at all bothered) to 6 (severely bothered).

5. Number of Participants With Withdrawals Due to Worsening of Asthma [16 weeks]

6. Assessment of Acceptability of the Device [16 weeks]

   Percentage of subjects that overall found it very easy or fairly easy to use the inhaler, based on inhaler acceptability questionnaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

• Written informed consent

• Adolescents aged 12-17 years & adults aged 18-65 years (both inclusive)

• Documented clinical history of severe asthma requiring prednisone/prednisolone therapy, high-intensity treatment ICS, OCS, LABA

• Stable OCS dose for ≥7 days before Screening Visit & during Screening Period.

• At least 80% compliant w/regular asthma medication per investigator at end of Screening Period

• Documented asthma reversibility within 5 yrs prior to/during Screening Period, or diagnosis of asthma that is incontrovertible per investigator

• Ability to use nDPI correctly, per investigator's review of completed inhaler operation checklist

• Ability to use eDiary correctly, assessed by investigator at end of Screening Period

• Ability to comply w/study procedures, including blood sampling

• Ability to perform technically satisfactory pulmonary function tests

• Available to complete all study visits before 12 noon

• BMI of 16-26 kg/m2 in adolescents and 18-32 kg/m2 in adults

• Oral PIF ≥40 L/min, using an appropriate device set to match resistance of inhaler

• Good health, except for presence of asthma, per medical history/physical examination

• Negative drug/alcohol/urine cotinine screen. Subjects must test negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, ethanol & opiates (unless given as prescription medicine)

• Non-smokers or ex-smokers with a smoking history of less than 10 pack-yrs (e.g. <20 cigarettes per day for 10 years or <40 cigarettes per day for 5 years) & stopped smoking for at least 1 year prior to Screening Visit. Smoking will not be permitted throughout study

• Female subjects of child-bearing potential must be using medically acceptable forms of contraception [abstinence, hormonal (oral/implant/transdermal/injection), in use for ≥3 consecutive months before first dose of study medication, double barrier (condom w/spermicide, or diaphragm w/spermicide), IUD, or vasectomised partner (≥6 months since vasectomy)].

Exclusion:

• Regular use (≥3 times/wk) of topical steroids to treat dermatitis/rhinitis/allergic conjunctivitis, within 28 days of Screening Visit

• Subjects who have/who have had, an upper/lower respiratory tract infection within 28 days of Screening Visit

• Subjects w/"brittle asthma

• Subjects w/asthma that required admission to an ICU and/or ventilation within previous 12 months

• Subjects whose comorbidities, per investigator's opinion, are major contributors to their respiratory symptoms (e.g. COPD, bronchiectasis, dysfunctional breathlessness, vocal cord dysfunction, gastro-oesophageal reflux)

• Previously/currently diagnosed as having Churg-Strauss syndrome

• Previously/currently diagnosed as having pulmonary eosinophilia

• History of lung cancer

• Subjects w/current diagnosis of HIV infection

• Active chronic hepatitis B or C infection

• Subjects who have clinically significant abnormality/finding from examination, tests, or history that may compromise subject safety, specifically any history of cardiac, renal or hepatic impairment

• Subjects with an abnormal ECG

• Persistent arterial hypotension, with average SBP readings of ≤95 mmHg

• Persistent elevation of blood pressure, with average SBP readings of ≥160 mmHg or average DBP readings of ≥100 mmHg

• Pregnant or lactating females

• Participation in another clinical study in 28 days prior to Screening Visit

• Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrectable hypokalaemia, or predisposition to low levels of serum potassium

• Current/history of drug/alcohol abuse/dependence per WHO criteria

• Inability to communicate well w/investigator

• Donation of ≥450 mL of blood/blood products within previous 3 months prior to screening

• History of allergy/intolerance/contraindications to corticosteroids/lactose, or severe allergy to milk proteins

• Consumption of alcohol- or caffeine-containing foods/beverages from midnight before or during Screening Visit

• History of medically diagnosed chronic respiratory diseases other than asthma (e.g. chronic obstructive pulmonary disease, ABPA in the absence of asthma)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vectura Clinical Trial Site 01001	Los Angeles	California	United States	90025
2	Vectura Clinial Trial Site 01005	Denver	Colorado	United States	80206
3	Vectura Clinical Trial Site 01006	Celebration	Florida	United States	34747
4	Vectura Clinical Trial Site 01015	Hialeah	Florida	United States	33018
5	Vectura Clinical Trial Site 01012	Miami Lakes	Florida	United States	33016
6	Vectura Clinical Trial Site 01014	Orlando	Florida	United States	32806
7	Vectura Clinical Trial Site 01003	Tampa	Florida	United States	33613
8	Vectura Clinical Trial Site 01011	Saint Louis	Missouri	United States	63110-1093
9	Vectura Clinical Trial Site 01013	Jersey City	New Jersey	United States	07306
10	Vectura Clinical Trial Site 01004	Bronx	New York	United States	10461
11	Vectura Clinical Trial Site 01007	El Paso	Texas	United States	79925
12	Vectura Clinical Trial Site 08006	Ruse		Bulgaria	7000
13	Vectura Clinical Trial Site 08005	Sofia		Bulgaria	1000
14	Vectura Clinical Trial Site 08001	Sofia		Bulgaria	1431
15	Vectura Clinical Trial Site 08003	Sofia		Bulgaria	1431
16	Vectura Clinical Trial Site 08007	Sofia		Bulgaria	1431
17	Vectura Clinical Trial Site 08004	Sofia		Bulgaria	1606
18	Vectura Clinical Trial Site 08002	Stara Zagora		Bulgaria	6000
19	Vectura Clinical Trial Site 08008	Varna		Bulgaria	9000
20	Vectura Clinical Trial Site 03006	Berlin		Germany	10717
21	Vectura Clinical Trial Site 03009	Berlin		Germany	12203
22	Vectura Clinical Trial Site 03004	Bonn		Germany	53119
23	Vectura Clinical Trial Site 03008	Donaustauf		Germany	93093
24	Vectura Clinical Trial Site 03003	Dortmund		Germany	44263
25	Vectura Clinical Trial Site 03007	Geesthacht		Germany	21502
26	Vectura Clinical Trial Site 03001	Hamburg		Germany	22767
27	Vectura Clinical Trial Site 03005	Heidelberg		Germany	69126
28	Vectura Clinical Trial Site 03002	Rudersdorf		Germany	15562
29	Vectura Clinical Trial Site 04001	Budapest		Hungary	1121
30	Vectura Clinical Trial Site 04004	Budapest		Hungary	1125
31	Vectura Clinical Trial Site 04003	Debrecen		Hungary	4032
32	Vectura Clinical Trial Site 04002	Rakoczi		Hungary	125 127
33	Vectura Clinical Trial Site 04005	Rakoczi		Hungary	7100
34	Vectura Clinical Trial Site 05008	Bialystok		Poland	15-003
35	Vectura Clinical Trial Site 05002	Bialystok		Poland	15-276
36	Vectura Clinical Trial Site 05010	Bialystok		Poland	15-430
37	Vectura Clinical Trial Site 05011	Krakow		Poland	31-024
38	Vectura Clinical Trial Site 05001	Lodz		Poland	90-153
39	Vectura Clinical Trial Site 05006	Lodz		Poland	90-153
40	Vectura Clinical Trial Site 05005	Lublin		Poland	20-552
41	Vectura Clinical Trial Site 05007	Tarnow		Poland	33-100
42	Vectura Clinical Trial Site 05003	Warszawa		Poland	02-097
43	Vectura Clinical Trial Site 05009	Wroclaw		Poland	51-162
44	Vectura Clinical Trial Site 05004	Zawadzkie		Poland	47-120
45	Vectura Clinical Trial Site 07001	Brasov		Romania	500086
46	Vectura Clinical Trial Site 07008	Bucuresti		Romania	010457
47	Vectura Clinical Trial Site 07005	Bucuresti		Romania	020671
48	Vectura Clinical Trial Site 07013	Bucuresti		Romania	030303
49	Vectura Clinical Trial Site 07003	Bucuresti		Romania	050554
50	Vectura Clinical Trial Site 07006	Cluj-Napoca		Romania	400371
51	Vectura Clinical Trial Site 07007	Cluj-Napoca		Romania	400371
52	Vectura Clinical Trial Site 07009	Cluj-Napoca		Romania	400371
53	Vectura Clinical Trial Site 07010	Cod		Romania	700115
54	Vectura Clinical Trial Site 07014	Craiova		Romania	200515
55	Vectura Clinical Trial Site 07002	Iasi		Romania	700376
56	Vectura Clinical Trial Site 07004	Marghita		Romania	415300
57	Vectura Clinical Trial Site 07012	Targu Mures		Romania	540543
58	Vectura Clinicl Trial Site 07011	Timis		Romania	300310
59	Vectura Clinical Trial Site 06013	AR Crimea		Ukraine	97403
60	Vectura Clinical Trial Site 06009	Donetsk		Ukraine	83099
61	Vectura Clinical Trial Site 06012	Ivano-Frankivsk		Ukraine	76018
62	Vectura Clinical Trial Site 06010	Kharkiv		Ukraine	61002
63	Vectura Clinical Trial Site 06001	Kharkiv		Ukraine	61035
64	Vectura Clinical Trial Site 06004	Kharkiv		Ukraine	61106
65	Vectura Clinical Trial Site 06006	Kyiv		Ukraine	02232
66	Vectura Clinical Trial Site 06002	Kyiv		Ukraine	03680
67	Vectura Clinical Trial Site 06015	Kyiv		Ukraine	3680
68	Vectura Clinical Trial Site 06003	Kyviv		Ukraine	04050
69	Vectura Clinical Trial Site 06008	Mykolaiv		Ukraine	54003
70	Vectura Clinical Trial Site 06011	Vinnitsa		Ukraine	21029
71	Vectura Clinical Trial Site 06007	Zaporizhzhia		Ukraine	69600
72	Vectura Clinical Trial Site 06014	Zaporizhzhya		Ukraine	69118
73	Vectura Clinical Trial Site 02003	Cottingham	Hull	United Kingdom	HU16 5JQ
74	Vectura Clinical Trial site 02002	Birmingham		United Kingdom	B9 5SS
75	Vectura Clinical Trial Site 02004	Manchester		United Kingdom	M23 9LT
76	Vectura Clinical Trial Site 02001	Newcastle		United Kingdom	NE7 7DN
77	Vectura Clinical Trial Site 02005	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Vectura Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vectura Limited
• ClinicalTrials.gov Identifier: NCT01720069
• Other Study ID Numbers: VR506/2/004
• First Posted: Nov 1, 2012
• Last Update Posted: Apr 21, 2020
• Last Verified: Apr 1, 2020

• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	197 subjects were randomised and 196 received at least one dose of study drug; 1 subject was randomised but not treated.

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Period Title: Overall Study
STARTED	62	71	63
Full Anaylsis Set	62	71	63
COMPLETED	57	56	48
NOT COMPLETED	5	15	15

Baseline Characteristics

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg	Total
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	Total of all reporting groups
Overall Participants	62	71	63	196
Age (Count of Participants)
<=18 years	0 0%	1 1.4%	0 0%	1 0.5%
Between 18 and 65 years	62 100%	70 98.6%	63 100%	195 99.5%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	40 64.5%	45 63.4%	42 66.7%	127 64.8%
Male	22 35.5%	26 36.6%	21 33.3%	69 35.2%
Region of Enrollment (participants) [Number]
Romania	16 25.8%	17 23.9%	16 25.4%	49 25%
Hungary	3 4.8%	3 4.2%	4 6.3%	10 5.1%
United States	2 3.2%	4 5.6%	4 6.3%	10 5.1%
Ukraine	15 24.2%	18 25.4%	14 22.2%	47 24%
Poland	15 24.2%	18 25.4%	16 25.4%	49 25%
United Kingdom	1 1.6%	1 1.4%	0 0%	2 1%
Bulgaria	6 9.7%	7 9.9%	6 9.5%	19 9.7%
Germany	4 6.5%	3 4.2%	3 4.8%	10 5.1%

Outcome Measures

1. Primary Outcome

Title	Mean Prednisone/Prednisolone Dose for Analysis (PDA) at End of Study (Week 16)
Description	The mean asthma control prednisone/prednisolone dose at end of study (week 16)
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) was analyzed, however 7 subjects are not included because they had no OCS dose adjustment assessment post-randomisation, and baseline values were not carried forward.

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	61	70	58
Mean (Standard Deviation) [mg]	4.55 (6.85)	4.31 (7.38)	3.97 (6.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.772
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for In-clinic Morning Pre-Dose Forced Expiratory Volume In 1 Second (FEV1)
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	71	63
Mean (Standard Deviation) [Liters]	0.06 (0.4)	0.02 (0.31)	0.06 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.891
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Asthma Control Questionnaire (ACQ-5) Mean Total Score
Description	Change from baseline to end of study (week 16) in 5 item asthma control questionnaire (ACQ-5) mean total score (range 0 (better) to 6 (worse)). The mean total score is calculated as the mean for each subject at each visit of 5 questions, each scored from 0 (better) to 6 (worse).
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set was analyzed, but number of patients represents subjects with both start of treatment baseline value and end of treatment value where a Last Observation Carried Forward (LOCF) approach was used to impute values of missing post-baseline visits; 1 subject had no post-dose ACQ-5 assessment, baseline value was not carried forward.

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	70	63
Mean (Standard Deviation) [score on a scale]	-0.67 (0.98)	-0.77 (1.15)	-0.39 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for In-clinic Weekly Morning Pre-dose Peak Expiratory Flow (PEF)
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	71	63
Mean (Standard Deviation) [L/min]	2 (45.7)	20.1 (51.7)	6.1 (53.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Weekly Average Asthma Night-time Symptom Score
Description	To measure the change from baseline to end of study for the weekly mean asthma night time symptom score, scored from 0 (not at all bothered) to 6 (severely bothered).
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	71	63
Mean (Standard Deviation) [score on a scale]	-0.3 (1)	-0.6 (1)	-0.2 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Number of Participants With Withdrawals Due to Worsening of Asthma
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	71	63
Count of Participants [Participants]	4 6.5%	11 15.5%	8 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 2 VR506 250 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.168
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dose 1 VR506 50 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.363
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dose 2 VR506 250 mcg, Dose 3 VR506 500 mcg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Assessment of Acceptability of the Device
Description	Percentage of subjects that overall found it very easy or fairly easy to use the inhaler, based on inhaler acceptability questionnaire
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose 1 VR506 50 mcg	Dose 2 VR506 250 mcg	Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
Measure Participants	62	71	63
Very easy	40 64.5%	49 69%	38 60.3%
Fairly easy	21 33.9%	21 29.6%	21 33.3%
Missing	1 1.6%	1 1.4%	4 6.3%

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Dose 1 VR506 50 mcg		Dose 2 VR506 250 mcg		Dose 3 VR506 500 mcg
Arm/Group Description	VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device		VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device		VR506 inhalation powder delivered via a new dry powder inhaler device VR506: VR506 inhalation powder delivered via a new dry powder inhaler device
All Cause Mortality
	Dose 1 VR506 50 mcg		Dose 2 VR506 250 mcg		Dose 3 VR506 500 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/71 (0%)		0/63 (0%)
Serious Adverse Events
	Dose 1 VR506 50 mcg		Dose 2 VR506 250 mcg		Dose 3 VR506 500 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/71 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Dose 1 VR506 50 mcg		Dose 2 VR506 250 mcg		Dose 3 VR506 500 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/62 (33.9%)		33/71 (46.5%)		25/63 (39.7%)
Blood and lymphatic system disorders
Eosinophilia	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Ear and labyrinth disorders
Middle Ear Effusion	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Eye disorders
Conjunctivitis	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Gastrointestinal disorders
Gastritis	1/62 (1.6%)	1	1/71 (1.4%)	1	0/63 (0%)	0
Abdominal Pain	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Food Poisoning	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
General disorders
Asthenia	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Hepatobiliary disorders
Cholecystitis Chronic	1/62 (1.6%)	1	0/71 (0%)	0	1/63 (1.6%)	1
Infections and infestations
Respiratory tract infection	1/62 (1.6%)	2	1/71 (1.4%)	1	2/63 (3.2%)	3
Acute sinusitis	0/62 (0%)	0	3/71 (4.2%)	4	1/63 (1.6%)	1
Oral candidiasis	2/62 (3.2%)	2	0/71 (0%)	0	0/63 (0%)	0
Bronchitis	1/62 (1.6%)	1	1/71 (1.4%)	1	1/63 (1.6%)	1
Phyaryngitis	1/62 (1.6%)	1	0/71 (0%)	0	1/63 (1.6%)	1
Cellulitis	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Cystisis	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Ear Infection	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Influenza	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Nasopharyngitis	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Oropharyngitis Fungal	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Otitis Media	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Pharyngitis Streptococcal	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Respiratory Tract Infection Viral	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Rhinitis	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Sinusitis	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Tonsillitis	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Tonsillitis Streptococcal	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Upper Respiratory Tract Infection	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Urinary Tract Infection	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Viral Pharyngitis	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Vulvovaginal Candidiasis	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Injury, poisoning and procedural complications
Joint Sprain	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Limb Injury	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Tibia Fracture	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Investigations
Alanine Aminotransferase Increased	1/62 (1.6%)	1	1/71 (1.4%)	1	0/63 (0%)	0
Aspartate Aminotransferase	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Blood Pressure Increased	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	2/62 (3.2%)	2	0/71 (0%)	0	1/63 (1.6%)	1
Hyperglycaemia	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/62 (0%)	0	0/71 (0%)	0	2/63 (3.2%)	3
Myalgia	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Pain in Extremity	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Spinal Osteoarthritis	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Nervous system disorders
Headache	2/62 (3.2%)	3	4/71 (5.6%)	4	1/63 (1.6%)	1
Dizziness	0/62 (0%)	0	2/71 (2.8%)	3	0/63 (0%)	0
Neuralgia	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Radiculitis	1/62 (1.6%)	1	0/71 (0%)	0	0/63 (0%)	0
Sciatica	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	12/62 (19.4%)	15	26/71 (36.6%)	35	12/63 (19%)	16
Oropharyngeal pain	2/62 (3.2%)	2	0/71 (0%)	0	2/63 (3.2%)	2
Nasal Congestion	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Painful Respiration	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Pharyngeal Erythema	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Skin and subcutaneous tissue disorders
Eczema	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Surgical and medical procedures
Tooth Extraction	0/62 (0%)	0	0/71 (0%)	0	1/63 (1.6%)	1
Vascular disorders
Hypertension	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0
Hypotension	0/62 (0%)	0	1/71 (1.4%)	1	0/63 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Vectura's agreements with its investigators may vary. Publication may be delayed for Sponsor review and revisions/deletions can be required. Furthermore, a delay to publication may be required by the Sponsor in order to take steps to protect its proprietary information and/or intellectual property rights.