A Comparison of VR647 and Conventionally Nebulized Budesonide in Healthy Volunteers and Adult Asthma Subjects
A Randomized, Open-label, Crossover Trial to Compare the Pharmacokinetics, Safety and Tolerability of Single Doses of VR647 Inhalation Suspension Delivered by the VR647 Inhalation System (VR647) With Single Doses of Budesonide Delivered by a Conventional Jet Nebulizer in Healthy Adult Volunteers and Adult Asthma Subjects
1 other identifier
interventional
34
1 country
2
Brief Summary
This is a three part, randomized, open-label, crossover, Phase 1 trial in adults. Parts 1 and 2 will enroll healthy male and female subjects. Part 3 will enroll subjects with mild asthma. This study will assess the pharmacokinetics, safety and tolerability of single doses of budesonide delivered by VR647 Inhalation System (AKITA® JET) with mouthpiece or face mask to single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS®) with mouthpiece or face mask.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 asthma
Started Feb 2017
Shorter than P25 for phase_1 asthma
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 22, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 22, 2017
CompletedFirst Submitted
Initial submission to the registry
July 4, 2019
CompletedFirst Posted
Study publicly available on registry
July 25, 2019
CompletedJuly 25, 2019
July 1, 2019
3 months
July 4, 2019
July 19, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
AUClast (area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration).
AUClast (area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration) compared for single doses of VR647 delivered by VR647 Inhalation System (AKITA JET) with single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS) via a mouthpiece in healthy volunteers, via a facemask in healthy volunteers, and via either a mouthpiece or a facemask in adult subjects with mild asthma.
pre-dose and at 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of nebulization for Parts 1, 2 and 3
AUCinf (area under the plasma concentration-time curve, from time 0 extrapolated to infinity).
AUCinf (area under the plasma concentration-time curve, from time 0 extrapolated to infinity) compared for single doses of VR647 delivered by VR647 Inhalation System (AKITA JET) with single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS) via a mouthpiece in healthy volunteers, via a facemask in healthy volunteers, and via either a mouthpiece or a facemask in adult subjects with mild asthma.
pre-dose and at 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of nebulization for Parts 1, 2 and 3
Cmax (maximum observed concentration).
Cmax (maximum observed concentration) compared for single doses of VR647 delivered by VR647 Inhalation System (AKITA JET) with single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS) via a mouthpiece in healthy volunteers, via a facemask in healthy volunteers, and via either a mouthpiece or a facemask in adult subjects with mild asthma.
pre-dose and at 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of nebulization for Parts 1, 2 and 3
Tmax (time to reach Cmax).
Tmax (time to reach Cmax) compared for single doses of VR647 delivered by VR647 Inhalation System (AKITA JET) with single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS) via a mouthpiece in healthy volunteers, via a facemask in healthy volunteers, and via either a mouthpiece or a facemask in adult subjects with mild asthma.
pre-dose and at 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of nebulization for Parts 1, 2 and 3
T1/2 (apparent first-order terminal elimination half-life).
T1/2 (apparent first-order terminal elimination half-life) compared for single doses of VR647 delivered by VR647 Inhalation System (AKITA JET) with single doses of budesonide delivered by a conventional jet nebulizer (PARI VIOS) via a mouthpiece in healthy volunteers, via a facemask in healthy volunteers, and via either a mouthpiece or a facemask in adult subjects with mild asthma.
pre-dose and at 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of nebulization for Parts 1, 2 and 3
Secondary Outcomes (3)
Number of adverse events (AEs) and serious adverse events (SAEs).
Part 1 and Part 2: approximately 64 days; Part 3: approximately 42 days
Number of adverse device effects (ADEs) and serious adverse device effects (SADEs).
Part 1 and Part 2: approximately 64 days; Part 3: approximately 42 days
Subjects with use of concomitant medications.
Part 1 and Part 2: approximately 64 days; Part 3: approximately 42 days
Study Arms (16)
Part 1, Arm A of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide.
Part 1, Arm B of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide.
Part 1, Arm C of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647.
Part 1, Arm D of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647.
Part 1, Arm E of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647.
Part 1, Arm F of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647.
Part 2, Arm A of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide.
Part 2, Arm B of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide.
Part 2, Arm C of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647.
Part 2, Arm D of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647.
Part 2, Arm E of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647, 10 breaths (60 µg) VR647.
Part 2, Arm F of single-dose, 6-treatment, 6-period crossover
OTHERSubjects received the following treatments in Periods 1 to 6 in a crossover fashion: 10 breaths (60 µg) VR647, 15 breaths (120 µg) VR647, 25 breaths (240 µg) VR647, 0.5 mg budesonide, 1 mg budesonide, 5 breaths (30 µg) VR647.
Part 3, Arm A of single-dose, 4-treatment, 4-period crossover
OTHERSubjects received the following treatments in Periods 1 to 4 in a crossover fashion: 15 breaths (120 µg) VR647 via mouthpiece, 15 breaths (120 µg) VR647 via facemask, 0.5 mg budesonide via mouthpiece, 0.5 mg budesonide via facemask.
Part 3, Arm B of single-dose, 4-treatment, 4-period crossover
OTHERSubjects received the following treatments in Periods 1 to 4 in a crossover fashion: 15 breaths (120 µg) VR647 via facemask, 0.5 mg budesonide via mouthpiece, 0.5 mg budesonide via facemask, 15 breaths (120 µg) VR647 via mouthpiece.
Part 3, Arm C of single-dose, 4-treatment, 4-period crossover
OTHERSubjects received the following treatments in Periods 1 to 4 in a crossover fashion: 0.5 mg budesonide via mouthpiece, 0.5 mg budesonide via facemask, 15 breaths (120 µg) VR647 via mouthpiece, 15 breaths (120 µg) VR647 via facemask.
Part 3, Arm D of single-dose, 4-treatment, 4-period crossover
OTHERSubjects received the following treatments in Periods 1 to 4 in a crossover fashion: 0.5 mg budesonide via facemask, 15 breaths (120 µg) VR647 via mouthpiece, 15 breaths (120 µg) VR647 via facemask, 0.5 mg budesonide via mouthpiece.
Interventions
The VR647 Inhalation System consists of the AKITA JET control unit that has an inspiration flow rate of 12 L/min, an AKITA JET nebulizer handset, a mouthpiece and dose-specific VR647 Smart Cards designed specifically for this trial.
The VR647 Inhalation System consists of the AKITA JET control unit that has an inspiration flow rate of 12 L/min, an AKITA JET nebulizer handset, a facemask and dose-specific VR647 Smart Cards designed specifically for this trial.
Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) will be delivered by a conventional jet nebulizer (PARI VIOS) with mouthpiece operated to sputtering.
Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) will be delivered by a conventional jet nebulizer (PARI VIOS) with facemask operated to sputtering.
Commercial Pulmicort Respules (budesonide inhalation suspension 0.5 mg/2 mL) will be delivered by a conventional jet nebulizer (PARI VIOS) with mouthpiece operated to sputtering.
Commercial Pulmicort Respules (budesonide inhalation suspension 0.5 mg/2 mL) will be delivered by a conventional jet nebulizer (PARI VIOS) with facemask operated to sputtering.
Eligibility Criteria
You may qualify if:
- Male or female subject
- Female subjects must have a negative pregnancy test at the Screening and Day -1 Visits (prior to dosing), must be using a reliable form of contraception throughout the trial, or must be of non-childbearing potential as follows:
- Be post-menopausal (their last menstrual period was at least 12 months ago), and have a serum follicle-stimulating hormone (FSH) level consistent with postmenopausal status as determined by the investigator, or
- Have undergone a hysterectomy, a bilateral oophorectomy or a bilateral salpingectomy
- Aged 18 to 55 years
- Hemoglobin level of ≥11.5 g/dL for females and ≥13.0 g/dL for males
- Weigh at least 50 kg, and body mass index (Quetelet index) in the range 18.0-32.0 kg/m2, inclusive
- Forced expiratory volume in 1 second (FEV1) of more than 1.69 L at the Screening Visit
- Ability to comprehend the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial
- Give written consent to participate after reading the consent form, and after having the opportunity to discuss the trial with the investigator or his/her delegate
- Documented clinical history of mild asthma (mild as defined by the National Asthma Evaluation and Prevention Program (NAEPP) guidelines) for at least 6 months before the Screening Visit, but otherwise healthy
- FEV1 reversibility (increase of at least 12% and 200 mL in absolute FEV1 from pre bronchodilator value within 15±5 minutes post bronchodilator) at the Screening Visit or during past 12 months
- Values for FEV1 of at least 80% of predicted value and normal FEV1/forced vital capacity (FVC; as defined by NAEPP guidelines). Assessment should be performed without treatment with β2-agonists. If a subject's FEV1 is outside that range at the Screening Visit, the test may be repeated once on another day during the Screening Period
You may not qualify if:
- Clinically relevant abnormal medical history, physical findings, ECG, or laboratory values at the screening assessment that could interfere with the objectives of the trial or the safety of the subject (excluding mild asthma in Part 3)
- Subjects who have impaired cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, respiratory (excluding mild asthma in Part 3), gastrointestinal, hepatic, hematological or any other system abnormalities
- Respiratory tract infection within 4 weeks before the Screening Visit
- History of surgery or medical intervention within 6 weeks before the Screening Visit, or planned surgery or medical intervention, that could interfere with the objectives of the trial or the safety of the subject
- Regular treatment (more than 1 month duration) with oral or parenteral corticosteroids in the last year prior to the Screening Visit
- Use of the following prescription medications within 28 days prior to the first dose:
- corticosteroids by any route, androgenic steroids (e.g., testosterone), ritonavir and similar drugs for HIV prophylaxis, ketoconazole, itraconazole or similar azole anti-fungal drugs and macrolide antibiotics (e.g., erythromycin)
- Presence or history of severe adverse reaction to any drug, or sensitivity to components of the trial medication
- Use of a prescription or over-the-counter medicine, nutritional and vitamin supplements, with the exception of acetaminophen and hormonal contraceptives, during the 7 days before the first dose of trial medication. For Part 3 only, inhaled short-acting β2-agonists in addition to acetaminophen and hormonal contraceptives are permitted
- Participation in another clinical trial of a new chemical entity, new device, or a prescription medicine within the 3 months before dosing, or participation within 5 half-lives of receiving an experimental drug (whichever is longer)
- Presence or history of drug or alcohol abuse, or intake of more than 21 units (14 units for women) of alcohol weekly
- Evidence of drug abuse on urine testing, or a positive test for alcohol
- Current smoker; or ex-smokers who (a) gave up less than 1 year ago, or (b) who have a history of more than 10 pack years. A pack year is calculated as the number of cigarettes per day multiplied by number of years smoked divided by 20
- Blood pressure and heart rate at the screening examination outside the ranges 90-140 mmHg systolic, 40-90 mm Hg diastolic, heart rate 40-100 beats/min
- Loss of more than 400 mL blood, e.g., as a blood donor, or donation of blood products, during the 3 months before the Screening Visit
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Vectura Limitedlead
Study Sites (2)
Celerion
Tempe, Arizona, 85283, United States
Anaheim Clinical Trials, LLC
Anaheim, California, 92801, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Gary Burgess, MD
Vectura Ltd
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 4, 2019
First Posted
July 25, 2019
Study Start
February 20, 2017
Primary Completion
May 22, 2017
Study Completion
May 22, 2017
Last Updated
July 25, 2019
Record last verified: 2019-07