Clinical trial NCT01472757: Clinical Study to Evaluate the Efficacy of VR506 Using a New Inhaler for the Treatment of Asthma
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Study to Evaluate the Efficacy and Safety of VR506 Inhaled From a New Inhaler in Adolescent and Adult Subjects With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Asthma
Lead sponsor: Vectura Limited
Sponsor class: INDUSTRY
First posted: 2011-11-16
Enrollment: 374
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: The purpose of the study is to evaluate the clinical efficacy of three doses of VR506 delivered via a new dry powder inhaler for the treatment of asthma.


Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Adolescents aged 12 to 17 years (inclusive) and adults aged 18 to 65 years (inclusive)
* Documented clinical history of asthma (i.e. made by a physician) for at least 6 months before the Screening Visit
* Documented asthma reversibility in the 5 years prior to or during Screening, or if the asthma reversibility criterion is not met at Screening, then a repeat test may be carried out at the end of the Run-In Period
* Subjects with asthma who, in the opinion of the investigator, require maintenance therapy with inhaled corticosteroids (ICS), are believed to have been regularly compliant with this therapy, and are therefore likely to deteriorate within 6 weeks following withdrawal of their usual ICS treatment
* Mild or moderate asthma, defined as:

  * Mild - good asthma control achieved by low-dose inhaled corticosteroid (daily dose 200-500 μg beclomethasone dipropionate or equivalent) with or without other low-intensity treatment (e.g. leukotriene modifiers or cromones) for at least 28 days before the Screening Visit
  * Moderate - good asthma control achieved by low- to moderate-dose ICS (daily dose 200-1000 μg beclomethasone dipropionate or equivalent), and long acting β2-agonist (LABA) or other extra treatment, for at least 28 days before the Screening Visit
* Ability to use the new inhaler correctly, based on investigator's review of the completed inhaler operation checklist
* Ability to use the eDiary correctly, assessed by the investigator during the Screening Period
* Ability to perform technically satisfactory pulmonary function tests
* Ability to comply with study procedures, including blood sampling
* Body mass index (BMI) of 16.0 to 26.0 kg/m2 in adolescents, and in adult subjects recruited in the Philippines, and 18.0 to 32.0 kg/m2 in adults recruited in other countries
* Available to complete all study visits
* Oral peak inspiratory flow (PIF) of at least 60 L/min; using an appropriate device set to match the resistance of the new dry powder inhaler (nDPI)
* Good health, except for the presence of asthma, according to medical history and physical examination
* Normal (i.e. non-clinically significant abnormality) 12-lead electrocardiogram (ECG)
* Negative drug, alcohol, and urine cotinine screen; subjects must test negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine (unless related to nicotine-containing therapies), ethanol, and opiates (unless given as a prescription medicine)
* Non-smokers or ex-smokers with a smoking history of less than 10 pack-years (e.g. \<20 cigarettes per day for 10 years or 40 cigarettes per day for 5 years) and stopped smoking for at least one year prior to the Screening Visit. Smoking will not be permitted throughout the study
* Female subjects of child-bearing potential must be using medically acceptable forms of contraception; approved forms of contraception are abstinence, hormonal (oral, implant, transdermal, or injection, in use for ≥3 consecutive months before the start of the Run-In Period), double barrier (condom with spermicide, diaphragm with spermicide), intrauterine device, or vasectomised partner (≥6 months since vasectomy)

Exclusion Criteria:

* Regular use (≥3 times per week) of topical steroids taken to treat dermatitis, rhinitis or allergic conjunctivitis, within 28 days of the Screening Visit
* Subjects who have or who have had an upper or lower respiratory tract infection within 28 days of the Screening Visit
* Subjects with asthma that required admission to an intensive care unit and/or ventilation within the previous 12 months
* History of lung cancer
* Subjects with "brittle asthma", defined as patients with asthma who either maintain over many months a wide variation (\>40%) in peak expiratory flow (PEF) between morning and evening measurements despite moderate to high doses of ICS, or are prone to acute, severe and often unpredictable attacks of asthma that may be fatal, on a background of apparently good asthma control
* History or current diagnosis of human immunodeficiency virus (HIV) infection
* Active chronic hepatitis B or C infection. If the patient's screening test is positive for hepatitis B surface antigen, the patient should be excluded unless the investigator, after a careful review of the patient's medical history and current laboratory tests of liver function, can exclude the possibility of recent or current infection
* Persistent arterial hypotension, with average systolic blood pressure (SBP) readings of ≤95 mmHg
* Subjects who have any clinically significant abnormality or 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 elevation of blood pressure, with average SBP readings of ≥160 mmHg or average diastolic blood pressure (DBP) readings of ≥100 mmHg
* Pregnant or lactating females
* Participation in another clinical study in the 28 days prior to the Screening Visit
* Current or a history of drug or alcohol abuse or dependence according to World Health Organization criteria in the 12 months prior to the Screening Visit or evidence of such abuse as indicated by laboratory assays conducted during the screening evaluation
* Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia, or predisposition to low levels of serum potassium
* Inability to communicate well with the investigator
* Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrected hypokalaemia, or predisposition to low levels of serum potassium
* Donation of ≥450 mL of blood or blood products within the previous 12 weeks prior to the Screening Visit
* History of allergy, intolerance or contraindications to corticosteroids, lactose, or severe allergy to milk proteins
* Consumption of alcohol- or caffeine-containing foods or beverages from midnight before or during the Screening Visit. The visit can be rescheduled once before the subject is excluded
* History of medically diagnosed chronic respiratory diseases (other than asthma) e.g. chronic obstructive pulmonary disease
* Subjects with previously clinically or radiologically diagnosed osteoporosis and/or those receiving regular treatment (more than 1 month duration) with oral or parenteral corticosteroids in the last year prior to the Screening Visit

Primary outcomes:
measure: Mean Change From Start of Treatment Baseline to End of Study (Week 12) for In-clinic Morning Pre-Dose Forced Expiratory Volume In 1 Second (FEV1)
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Number of Participants With Withdrawals Due to Worsening of Asthma
timeFrame: 12 weeks
measure: Mean Change From Start of Treatment Baseline to End of Study (Week 12) for In-clinic Weekly Morning Pre-dose Peak Expiratory Flow (PEF)
timeFrame: Baseline and 12 weeks
measure: Assessment of Acceptability of the Device
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Vectura Clinical Trial Site 10038
state: California
city: Los Angeles
country: United States
facility: Vectura Clinical Trial Site 10031
state: California
city: Mission Viejo
country: United States
facility: Vectura Clinical Trial Site 10044
state: California
city: Orange
country: United States
facility: Vectura Clinical Trial Site 10022
state: California
city: Rancho Mirage
country: United States
facility: Vectura Clinical Trial Site 10014
state: California
city: Rolling Hills Estates
country: United States
facility: Vectura Clinical Trial Site 10027
state: California
city: San Jose
country: United States
facility: Vectura Clinical Trial Site 10033
state: California
city: Vista
country: United States
facility: Vectura Clinical Trial Site 10016
state: California
city: Centennial
country: United States
facility: Vectura Clinical Trial Site 10023
state: Colorado
city: Colorado Springs
country: United States
facility: Vectura Clinical Trial Site 10001
state: Colorado
city: Denver
country: United States
facility: Vectura Clinical Trial Site 10025
state: Colorado
city: Sarasota
country: United States
facility: Vectura Clinical Trial Site 10041
state: Florida
city: Albany
country: United States
facility: Vectura Clinical Trial Site 10011
state: Georgia
city: Metairie
country: United States
facility: Vectura Clinical Trial Site 10002
state: Louisiana
city: Baltimore
country: United States
facility: Vectura Clinical Trial Site 10042
state: Maryland
city: North Dartmouth
country: United States
facility: Vectura Clinical Trial Site 10029
state: Massachusetts
city: Plymouth
country: United States
facility: Vectura Clinical Trial Site 10008
state: Minnesota
city: Warrensburg
country: United States
facility: Vectura Clinical Trial Site 10020
state: Missouri
city: Missoula
country: United States
facility: Vectura Clinical Trial Site 10009
state: Montana
city: Bellevue
country: United States
facility: Vectura Clinical Trial Site 10034
state: Nebraska
city: Omaha
country: United States
facility: Vectura Clinical Trial Site 10035
state: Nebraska
city: Omaha
country: United States
facility: Vectura Clinical Trial Site 10015
state: Nebraska
city: Rochester
country: United States
facility: Vectura Clinical Trial Site 10040
state: New York
city: Sylvania
country: United States
facility: Vectura Clinical Trial Site 10010
state: Ohio
city: Oklahoma City
country: United States
facility: Vectura Clinical Trial Site 10017
state: Oklahoma
city: Medford
country: United States
facility: Vectura Clinical Trial Site 10028
state: Oregon
city: Portland
country: United States
facility: Vectura Clinical Trial Site 10024
state: Oregon
city: Upland
country: United States
facility: Vectura Clinical Trial Site 10021
state: Pennsylvania
city: Charleston
country: United States
facility: Vectura Clinical Trial Site 10003
state: South Carolina
city: Boerne
country: United States
facility: Vectura Clinical Trial Site 10019
state: Texas
city: Waco
country: United States
facility: Vectura Clinical Trial Site 10039
state: Texas
city: Draper
country: United States
facility: Vectura Clinical Trial Site 10004
state: Utah
city: Lipa City
country: Philippines
facility: Vectura Clinical Trial Site 31001
state: Batangas
city: Davao City
country: Philippines
facility: Vectura Clinical Trial Site 31002
city: Iloilo City
country: Philippines
facility: Vectura Clinical Trial Site 31003
city: Pasig City
country: Philippines
facility: Vectura Clinical Trial Site 31004
city: Quezon City
country: Philippines
facility: Vectura Clinical Trial Site 31005
city: Quezon City
country: Philippines
facility: Vectura Clinical Trial Site 31007
city: Bialystok
country: Poland
facility: Vectura Clinical Trial Site 20018
city: Biołystok
country: Poland
facility: Vectura Clinical Trial Site 20013
city: Krakow
country: Poland
facility: Vectura Clinical Trial Site 20015
city: Krakow
country: Poland
facility: Vectura Clinical Trial Site 20019
city: Lublin
country: Poland
facility: Vectura Clinical Trial Site 20012
city: Ostrów Wielkopolski
country: Poland
facility: Vectura Clinical Trial Site 20008
city: Poznań
country: Poland
facility: Vectura Clinical Trial Site 20003
city: Poznań
country: Poland
facility: Vectura Clinical Trial Site 20005
city: Skiemiewice
country: Poland
facility: Vectura Clinical Trial Site 20016
city: Tarnow
country: Poland
facility: Vectura Clinical Trial Site 20021
city: Warszawa
country: Poland
facility: Vectura Clinical Trial Site 20010
city: Wroclaw
country: Poland
facility: Vectura Clinical Trial Site 20001
city: Wrocław
country: Poland
facility: Vectura Clinical Trial Site 20006
city: Zawadzkie
country: Poland
facility: Vectura Clinical Trial Site 20014
city: Łodź
country: Poland
facility: Vectura Clinical Trial Site 20007
city: Łódź
country: Poland
facility: Vectura Clinical Trial Site 20009
city: Brasov
country: Romania
facility: Vectura Clinical Trial Site 21002
city: Bucuresti
country: Romania
facility: Vectura Clinical Trial Site 21011
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 21004
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 21009
city: Cluj-Napoca
country: Romania
facility: Vectura Clinical Trial Site 21010
city: Iasi
country: Romania
facility: Vectura Clinical Trial Site 21007
city: Iasi
country: Romania
facility: Vectura Clinical Trial Site 21008
city: Judetul Cluj
country: Romania
facility: Vectura Clinical Trial Site 21013
city: Judetul Iasi
country: Romania
facility: Vectura Clinical Trial Site 21012
city: Targu-Mures
country: Romania
facility: Vectura Clinical Trial Site 21001
city: Timisoara
country: Romania
facility: Vectura Clinical Trial Site 21005
city: Donetsk
country: Ukraine
facility: Vectura Clinical Trial Site 23013
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 23005
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 23004
city: Kharkiv
country: Ukraine
facility: Vectura Clinical Trial Site 23010
city: Kiev
country: Ukraine
facility: Vectura Clinical Trial Site 23012
city: Kiev
country: Ukraine
facility: Vectura Clinical Trial Site 23002
city: Kiev
country: Ukraine
facility: Vectura Clinical Trial Site 23009
city: Kiev
country: Ukraine
facility: Vectura Clinical Trial Site 23011
city: Kiev
country: Ukraine
facility: Vectura Clinical Trial Site 23017
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 23001
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 23003
city: Kyiv
country: Ukraine
facility: Vectura Clinical Trial Site 23018
city: Odesa
country: Ukraine
facility: Vectura Clinical Trial Site 23007
city: Simferopol
country: Ukraine
facility: Vectura Clinical Trial Site 23015
city: Vinnytsya
country: Ukraine
facility: Vectura Clinical Trial Site 23014
city: Zaporizhzhya
country: Ukraine
facility: Vectura Clinical Trial Site 23008
city: Zaporizhzhya
country: Ukraine
facility: Vectura Clinical Trial Site 23016
Study officials:
affiliation: Aarhus University Hospital
name: Ronald Dahl, Dr.
role: PRINCIPAL_INVESTIGATOR
References: