A Study of the Pharmacokinetics, Safety and Tolerability of Single Doses of VR647 Inhalation Suspension Administered Using the VR647 Inhalation System in Children With Wheezing, Reactive Airway Disease or Mild Asthma
- Conditions
- WheezingReactive Airway DiseaseMild Asthma
- Interventions
- Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
- Registration Number
- NCT03421730
- Lead Sponsor
- Vectura Limited
- Brief Summary
The primary objective of this study is to evaluate budesonide levels in the blood following inhalation of single doses of VR647 Inhalation Suspension in children with wheezing, reactive airway disease or mild asthma using a nebulizer, the VR647 Inhalation System. Secondary objectives include the evaluation of the safety and tolerability of VR647 Inhalation Suspension administered using the VR647 Inhalation System.
The study consists of four visits; a screening visit (Visit 1), two dosing days (Visits 2 and 3) and a follow-up visit (Visit 4). On each dosing day a single dose of treatment will be administered. Treatment allocation at Visits 2 and 3 is determined by a balanced incomplete block design.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- Male or pre-menarchal female subjects.
- Aged 4 to 8 years, inclusive.
- Diagnosis of wheezing, reactive airway disease or mild asthma confirmed by a physician at least 3 months prior to screening.
- Wheezing, reactive airway disease or mild asthma controlled by intermittent or regular non-steroidal medications commonly used for asthma, such as short-acting β2-agonists (SABAs) or leukotriene receptor antagonists (LTRAs), for a minimum of 28 days prior to the Screening Visit.
- Body weight ≥15 kg.
- Subject is able to demonstrate the ability to use the VR647 Inhalation System and the conventional jet nebulizer effectively during training.
Key
- Clinically relevant abnormality or medical condition (other than wheezing, reactive airway disease or mild asthma) identified at the screening assessment that, in the opinion of the investigator, could interfere with the objectives of the trial or the safety of the subject. The sponsor's medical officer should be consulted in case of any doubt.
- Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episodes.
- Subjects currently using long-acting β2-agonists.
- Use of the following prescription medications within 28 days prior to the first treatment day: corticosteroids by any route and drugs that inhibit cytochrome P450 3A4.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description AB - VR647 5 breaths, then VR647 10 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System AD - VR647 5 breaths, then Pulmicort 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty BA - VR647 10 breaths, then VR647 5 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System BC - VR647 10 breaths, then VR647 20 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System AC - VR647 5 breaths, then VR647 20 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System BD - VR647 10 breaths, then Pulmicort VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty CB - VR647 20 breaths, then VR647 10 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System AD - VR647 5 breaths, then Pulmicort VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty CD - VR647 20 breaths, then Pulmicort VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty BD - VR647 10 breaths, then Pulmicort 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty CA - VR647 20 breaths, then VR647 5 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System CD - VR647 20 breaths, then Pulmicort 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty DA - Pulmicort, then VR647 5 breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System DA - Pulmicort, then VR647 5 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System DB - Pulmicort, then VR647 10 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System DB - Pulmicort, then VR647 10 breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System DC - Pulmicort, then VR647 20 breaths VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System DC - Pulmicort, then VR647 20 breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
- Primary Outcome Measures
Name Time Method Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). Cmax is the maximum observed concentration.
AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). AUClast is the area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration (Clast).
AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). AUCinf is the area under the plasma concentration-time curve, from time 0 extrapolated to infinity. AUCinf is calculated as the sum of AUClast plus the ratio of the last measurable plasma concentration (Clast) to the elimination rate constant (λz).
Tlast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). Tlast is the time of the last measurable concentration (Clast).
Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). Tmax is the time to reach Cmax.
T1/2 of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3). T1/2 is the apparent first-order terminal elimination half-life.
- Secondary Outcome Measures
Name Time Method Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10). Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3). The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. Question 10 asks about willingness to continue with the device(s) used in the trial. Parents/legal guardians were asked to indicate how willing they would be for their child to use the nebulizer used during the study, providing a number between 0 (unwilling) and 100 (willing).
Changes in Vital Signs (Temperature) Baseline to Day 1 0.5 hours post-dose Mean values for temperature from pre-dose to 0.5 hours post-dose.
Changes in Physical Examination Visit 1, and Day 8 of Visit 3. Physical examination data were listed. The number of participants with a change in physical examination status (i.e. from normal to abnormal, or from abnormal to normal) is presented below.
Use of Concomitant Medications Visit 1 Number of subjects using concomitant medications.
Mean Modified PASAPQ Satisfaction Score (Q9). Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3). The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. Question 9 asks for overall satisfaction with the device(s) used in the trial. Question 9 was answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Changes in Vital Signs (Respiration Rate) Baseline to Day 1 0.5 hours post-dose Mean values for respiratory rate from pre-dose to 0.5 hours post-dose.
Mean Modified Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score (Q1 to Q8). Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3). The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. The first 8 questions generate the total score domain. Data from this questionnaire were listed by subject and summarized by treatment. The results from Questions 1 through 8 were added for each subject to generate the Total Score (n = Q1+Q2+Q3+Q4+Q5+Q6+Q7+Q8) and expressed as percentage of maximum total score (i.e., (n/56)\*100). Questions 1 to 8 were answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Mean Modified PASAPQ Performance Score Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3). The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices; it was originally a 15-item questionnaire, with performance assessed over 7 items. The modified PASAPQ (mPASAPQ) has 10 questions, including only 4 from the performance domain; the 3 questions not included were dropped from the mPASAPQ as they were not applicable to patient population and device under study. Questions 1, 2, 6, and 7 were assessed, covering satisfaction with nebulizer reliability, ease of inhalation, use and treatment time. Although specified in the protocol, the mPASAPQ performance score was not summarized in the efficacy analysis. The results for each question are presented below, however it was not considered appropriate to analyze the performance domain, as it is not possible to verify the validity of the questionnaire utilising only 4 of the original 7 questions. Questions were answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Changes in Vital Signs (Heart Rate) Baseline to Day 1 0.5 hours post-dose Mean values for heart rate from pre-dose to 0.5 hours post-dose.
Changes in Vital Signs (Blood Pressure) Baseline to Day 1 0.5 hours post-dose Mean values for blood pressure from pre-dose to 0.5 hours post-dose.
Trial Locations
- Locations (3)
Vectura Study Site 0001
🇺🇸Tulsa, Oklahoma, United States
Vectura Study Site 0003
🇺🇸Colorado Springs, Colorado, United States
Vectura Study Site 0002
🇺🇸Raleigh, North Carolina, United States