Clinical trial NCT01720069: Clinical Study to Evaluate the Efficacy and Safety of VR506 Using a New Inhaler for the Treatment of Asthma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Asthma
Lead sponsor: Vectura Limited
Sponsor class: INDUSTRY
First posted: 2012-11-01
Enrollment: 197
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Mean Prednisone/Prednisolone Dose for Analysis (PDA) at End of Study (Week 16)
timeFrame: 16 weeks
Secondary outcomes:
measure: 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)
timeFrame: Baseline and 16 weeks
measure: Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Asthma Control Questionnaire (ACQ-5) Mean Total Score
timeFrame: Baseline and 16 weeks
measure: Mean Change From Start of Treatment Baseline to End of Study (Week 16) for In-clinic Weekly Morning Pre-dose Peak Expiratory Flow (PEF)
timeFrame: Baseline and 16 weeks
measure: Mean Change From Start of Treatment Baseline to End of Study (Week 16) for Weekly Average Asthma Night-time Symptom Score
timeFrame: Baseline and 16 weeks
measure: Number of Participants With Withdrawals Due to Worsening of Asthma
timeFrame: 16 weeks
measure: Assessment of Acceptability of the Device
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Vectura Clinical Trial Site 01001
state: California
city: Denver
country: United States
facility: Vectura Clinial Trial Site 01005
state: Colorado
city: Celebration
country: United States
facility: Vectura Clinical Trial Site 01006
state: Florida
city: Hialeah
country: United States
facility: Vectura Clinical Trial Site 01015
state: Florida
city: Miami Lakes
country: United States
facility: Vectura Clinical Trial Site 01012
state: Florida
city: Orlando
country: United States
facility: Vectura Clinical Trial Site 01014
state: Florida
city: Tampa
country: United States
facility: Vectura Clinical Trial Site 01003
state: Florida
city: Saint Louis
country: United States
facility: Vectura Clinical Trial Site 01011
state: Missouri
city: Jersey City
country: United States
facility: Vectura Clinical Trial Site 01013
state: New Jersey
city: Bronx
country: United States
facility: Vectura Clinical Trial Site 01004
state: New York
city: El Paso
country: United States
facility: Vectura Clinical Trial Site 01007
state: Texas
city: Ruse
country: Bulgaria
facility: Vectura Clinical Trial Site 08006
city: Sofia
country: Bulgaria
facility: Vectura Clinical Trial Site 08005
city: Sofia
country: Bulgaria
facility: Vectura Clinical Trial Site 08001
city: Sofia
country: Bulgaria
facility: Vectura Clinical Trial Site 08003
city: Sofia
country: Bulgaria
facility: Vectura Clinical Trial Site 08007
city: Sofia
country: Bulgaria
facility: Vectura Clinical Trial Site 08004
city: Stara Zagora
country: Bulgaria
facility: Vectura Clinical Trial Site 08002
city: Varna
country: Bulgaria
facility: Vectura Clinical Trial Site 08008
city: Berlin
country: Germany
facility: Vectura Clinical Trial Site 03006
city: Berlin
country: Germany
facility: Vectura Clinical Trial Site 03009
city: Bonn
country: Germany
facility: Vectura Clinical Trial Site 03004
city: Donaustauf
country: Germany
facility: Vectura Clinical Trial Site 03008
city: Dortmund
country: Germany
facility: Vectura Clinical Trial Site 03003
city: Geesthacht
country: Germany
facility: Vectura Clinical Trial Site 03007
city: Hamburg
country: Germany
facility: Vectura Clinical Trial Site 03001
city: Heidelberg
country: Germany
facility: Vectura Clinical Trial Site 03005
city: Rudersdorf
country: Germany
facility: Vectura Clinical Trial Site 03002
city: Budapest
country: Hungary
facility: Vectura Clinical Trial Site 04001
city: Budapest
country: Hungary
facility: Vectura Clinical Trial Site 04004
city: Debrecen
country: Hungary
facility: Vectura Clinical Trial Site 04003
city: Rakoczi
country: Hungary
facility: Vectura Clinical Trial Site 04002
city: Rakoczi
country: Hungary
facility: Vectura Clinical Trial Site 04005
city: Bialystok
country: Poland
facility: Vectura Clinical Trial Site 05008
city: Bialystok
country: Poland
facility: Vectura Clinical Trial Site 05002
city: Bialystok
country: Poland
facility: Vectura Clinical Trial Site 05010
city: Krakow
country: Poland
facility: Vectura Clinical Trial Site 05011
city: Lodz
country: Poland
facility: Vectura Clinical Trial Site 05001
city: Lodz
country: Poland
facility: Vectura Clinical Trial Site 05006
city: Lublin
country: Poland
facility: Vectura Clinical Trial Site 05005
city: Tarnow
country: Poland
facility: Vectura Clinical Trial Site 05007
city: Warszawa
country: Poland
facility: Vectura Clinical Trial Site 05003
city: Wroclaw
country: Poland
facility: Vectura Clinical Trial Site 05009
city: Zawadzkie
country: Poland
facility: Vectura Clinical Trial Site 05004
city: Brasov
country: Romania
facility: Vectura Clinical Trial Site 07001
city: Bucuresti
country: Romania
facility: Vectura Clinical Trial Site 07008
city: Bucuresti
country: Romania
facility: Vectura Clinical Trial Site 07005
city: Bucuresti
country: Romania
facility: Vectura Clinical Trial Site 07013
city: Bucuresti
country: Romania
facility: Vectura Clinical Trial Site 07003
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 07006
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 07007
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 07009
city: Cod
country: Romania
facility: Vectura Clinical Trial Site 07010
city: Craiova
country: Romania
facility: Vectura Clinical Trial Site 07014
city: Iasi
country: Romania
facility: Vectura Clinical Trial Site 07002
city: Marghita
country: Romania
facility: Vectura Clinical Trial Site 07004
city: Targu Mures
country: Romania
facility: Vectura Clinical Trial Site 07012
city: Timis
country: Romania
facility: Vectura Clinicl Trial Site 07011
city: AR Crimea
country: Ukraine
facility: Vectura Clinical Trial Site 06013
city: Donetsk
country: Ukraine
facility: Vectura Clinical Trial Site 06009
city: Ivano-Frankivsk
country: Ukraine
facility: Vectura Clinical Trial Site 06012
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 06010
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 06001
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 06004
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 06006
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 06002
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 06015
city: Kyviv
country: Ukraine
facility: Vectura Clinical Trial Site 06003
city: Mykolaiv
country: Ukraine
facility: Vectura Clinical Trial Site 06008
city: Vinnitsa
country: Ukraine
facility: Vectura Clinical Trial Site 06011
city: Zaporizhzhia
country: Ukraine
facility: Vectura Clinical Trial Site 06007
city: Zaporizhzhya
country: Ukraine
facility: Vectura Clinical Trial Site 06014
city: Cottingham
country: United Kingdom
facility: Vectura Clinical Trial Site 02003
state: Hull
city: Birmingham
country: United Kingdom
facility: Vectura Clinical Trial site 02002
city: Manchester
country: United Kingdom
facility: Vectura Clinical Trial Site 02004
city: Newcastle
country: United Kingdom
facility: Vectura Clinical Trial Site 02001
city: Nottingham
country: United Kingdom
facility: Vectura Clinical Trial Site 02005
Study officials:
References: