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

Asthma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01720069
• Other study ID #: VR506/2/004
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 2012
• Est. completion date: October 2013

Study information

• Verified date: April 2020
• Source: Vectura Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• VR506
VR506 inhalation powder delivered via a new dry powder inhaler device

Locations

Country	Name	City	State
Bulgaria	Vectura Clinical Trial Site 08006	Ruse
Bulgaria	Vectura Clinical Trial Site 08001	Sofia
Bulgaria	Vectura Clinical Trial Site 08003	Sofia
Bulgaria	Vectura Clinical Trial Site 08004	Sofia
Bulgaria	Vectura Clinical Trial Site 08005	Sofia
Bulgaria	Vectura Clinical Trial Site 08007	Sofia
Bulgaria	Vectura Clinical Trial Site 08002	Stara Zagora
Bulgaria	Vectura Clinical Trial Site 08008	Varna
Germany	Vectura Clinical Trial Site 03006	Berlin
Germany	Vectura Clinical Trial Site 03009	Berlin
Germany	Vectura Clinical Trial Site 03004	Bonn
Germany	Vectura Clinical Trial Site 03008	Donaustauf
Germany	Vectura Clinical Trial Site 03003	Dortmund
Germany	Vectura Clinical Trial Site 03007	Geesthacht
Germany	Vectura Clinical Trial Site 03001	Hamburg
Germany	Vectura Clinical Trial Site 03005	Heidelberg
Germany	Vectura Clinical Trial Site 03002	Rudersdorf
Hungary	Vectura Clinical Trial Site 04001	Budapest
Hungary	Vectura Clinical Trial Site 04004	Budapest
Hungary	Vectura Clinical Trial Site 04003	Debrecen
Hungary	Vectura Clinical Trial Site 04002	Rakoczi
Hungary	Vectura Clinical Trial Site 04005	Rakoczi
Poland	Vectura Clinical Trial Site 05002	Bialystok
Poland	Vectura Clinical Trial Site 05008	Bialystok
Poland	Vectura Clinical Trial Site 05010	Bialystok
Poland	Vectura Clinical Trial Site 05011	Krakow
Poland	Vectura Clinical Trial Site 05001	Lodz
Poland	Vectura Clinical Trial Site 05006	Lodz
Poland	Vectura Clinical Trial Site 05005	Lublin
Poland	Vectura Clinical Trial Site 05007	Tarnow
Poland	Vectura Clinical Trial Site 05003	Warszawa
Poland	Vectura Clinical Trial Site 05009	Wroclaw
Poland	Vectura Clinical Trial Site 05004	Zawadzkie
Romania	Vectura Clinical Trial Site 07001	Brasov
Romania	Vectura Clinical Trial Site 07003	Bucuresti
Romania	Vectura Clinical Trial Site 07005	Bucuresti
Romania	Vectura Clinical Trial Site 07008	Bucuresti
Romania	Vectura Clinical Trial Site 07013	Bucuresti
Romania	Vectura Clinical Trial Site 07006	Cluj-Napoca
Romania	Vectura Clinical Trial Site 07007	Cluj-Napoca
Romania	Vectura Clinical Trial Site 07009	Cluj-Napoca
Romania	Vectura Clinical Trial Site 07010	Cod
Romania	Vectura Clinical Trial Site 07014	Craiova
Romania	Vectura Clinical Trial Site 07002	Iasi
Romania	Vectura Clinical Trial Site 07004	Marghita
Romania	Vectura Clinical Trial Site 07012	Targu Mures
Romania	Vectura Clinicl Trial Site 07011	Timis
Ukraine	Vectura Clinical Trial Site 06013	AR Crimea
Ukraine	Vectura Clinical Trial Site 06009	Donetsk
Ukraine	Vectura Clinical Trial Site 06012	Ivano-Frankivsk
Ukraine	Vectura Clinical Trial Site 06001	Kharkiv
Ukraine	Vectura Clinical Trial Site 06004	Kharkiv
Ukraine	Vectura Clinical Trial Site 06010	Kharkiv
Ukraine	Vectura Clinical Trial Site 06002	Kyiv
Ukraine	Vectura Clinical Trial Site 06006	Kyiv
Ukraine	Vectura Clinical Trial Site 06015	Kyiv
Ukraine	Vectura Clinical Trial Site 06003	Kyviv
Ukraine	Vectura Clinical Trial Site 06008	Mykolaiv
Ukraine	Vectura Clinical Trial Site 06011	Vinnitsa
Ukraine	Vectura Clinical Trial Site 06007	Zaporizhzhia
Ukraine	Vectura Clinical Trial Site 06014	Zaporizhzhya
United Kingdom	Vectura Clinical Trial site 02002	Birmingham
United Kingdom	Vectura Clinical Trial Site 02003	Cottingham	Hull
United Kingdom	Vectura Clinical Trial Site 02004	Manchester
United Kingdom	Vectura Clinical Trial Site 02001	Newcastle
United Kingdom	Vectura Clinical Trial Site 02005	Nottingham
United States	Vectura Clinical Trial Site 01004	Bronx	New York
United States	Vectura Clinical Trial Site 01006	Celebration	Florida
United States	Vectura Clinial Trial Site 01005	Denver	Colorado
United States	Vectura Clinical Trial Site 01007	El Paso	Texas
United States	Vectura Clinical Trial Site 01015	Hialeah	Florida
United States	Vectura Clinical Trial Site 01013	Jersey City	New Jersey
United States	Vectura Clinical Trial Site 01001	Los Angeles	California
United States	Vectura Clinical Trial Site 01012	Miami Lakes	Florida
United States	Vectura Clinical Trial Site 01014	Orlando	Florida
United States	Vectura Clinical Trial Site 01011	Saint Louis	Missouri
United States	Vectura Clinical Trial Site 01003	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vectura Limited

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany,  Hungary,  Poland,  Romania,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Prednisone/Prednisolone Dose for Analysis (PDA) at End of Study (Week 16)	The mean asthma control prednisone/prednisolone dose at end of study (week 16)	16 weeks
Secondary	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
Secondary	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Asthma Control Questionnaire (ACQ-5) Mean Total Score	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).	Baseline and 16 weeks
Secondary	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
Secondary	Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Weekly Average Asthma Night-time Symptom Score	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).	Baseline and 16 weeks
Secondary	Number of Participants With Withdrawals Due to Worsening of Asthma		16 weeks
Secondary	Assessment of Acceptability of the Device	Percentage of subjects that overall found it very easy or fairly easy to use the inhaler, based on inhaler acceptability questionnaire	16 weeks