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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

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ClinicalTrials.gov Identifier: NCT03421730
Recruitment Status : Recruiting
First Posted : February 5, 2018
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Wheezing Reactive Airway Disease Mild Asthma Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer Phase 1

Detailed Description:

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. Blood samples will be collected on eight occasions from pre-dose up to 8 hours post-dose at each dosing visit. Treatment allocation at Visits 2 and 3 is determined by a balanced incomplete block design.

The screening period (including Visit 1) is between 2 and 30 days duration; there is a washout period of 4 to 10 days between each dose (Visits 2 and 3) and the follow-up safety assessment (Visit 4) will occur 5 to 9 days after Visit 3. Subjects and their parent(s)/legal guardian(s) have the option of an overnight stay the day before dosing (Day -1, Visit 2 and Day 7, Visit 3).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is an open label, randomized, balanced, incomplete block design trial. Eligible subjects will be randomized to 1 of 12 treatment sequences (A,B), (A,C), (A,D), (B,A), (B,C), (B,D), (C,A), (C,B), (C,D), (D,A), (D,B) or (D,C), corresponding to the following treatment regimens:

  • (A) 5 four-second inhalations of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
  • (B) 10 four-second inhalations of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
  • (C) 20 four-second inhalations of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
  • (D) 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty

The treatment period comprises 2 dosing visits. Each subject will receive their first treatment regimen during Visit 2 and their second treatment regimen during Visit 3.

Masking: None (Open Label)
Masking Description: This is an open label trial.
Primary Purpose: Treatment
Official Title: A Single-dose, Open-label, Randomized, Incomplete Block Design Trial to Characterize the Pharmacokinetics of VR647 Inhalation Suspension Delivered by the VR647 Inhalation System and Single Doses of Budesonide Delivered by a Conventional Jet Nebulizer in Pediatric Subjects Aged 4 to 8 Years With Wheezing, Reactive Airway Disease or Mild Asthma
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Budesonide

Arm Intervention/treatment
Experimental: (A)
5 four-second inhalations of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
The VR647 Inhalation System consists of the VR647 Inhalation System 1 control unit that has an inspiration flow rate of 6 L/min, a VR647 nebulizer handset, a mouthpiece and VR647 Smart Cards designed specifically for this trial.

Experimental: (B)
10 four-second inhalations of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
The VR647 Inhalation System consists of the VR647 Inhalation System 1 control unit that has an inspiration flow rate of 6 L/min, a VR647 nebulizer handset, a mouthpiece and VR647 Smart Cards designed specifically for this trial.

Experimental: (C)
20 four-second inhalations of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
The VR647 Inhalation System consists of the VR647 Inhalation System 1 control unit that has an inspiration flow rate of 6 L/min, a VR647 nebulizer handset, a mouthpiece and VR647 Smart Cards designed specifically for this trial.

Experimental: (D)
1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty
Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) will be delivered by a conventional jet nebulizer operated to sputtering.




Primary Outcome Measures :
  1. AUClast of plasma budesonide (VR647 Inhalation Suspension or Pulmicort Respules). [ Time Frame: 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 concentration-time curve, from time 0 to the last collection time point.

  2. AUCinf of plasma budesonide (VR647 Inhalation Suspension or Pulmicort Respules). [ Time Frame: 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 concentration-time curve, from time 0 to infinite time.

  3. Cmax of plasma budesonide (VR647 Inhalation Suspension or Pulmicort Respules). [ Time Frame: 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.

  4. Tmax of plasma budesonide (VR647 Inhalation Suspension or Pulmicort Respules). [ Time Frame: 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.

  5. T1/2 of plasma budesonide (VR647 Inhalation Suspension or Pulmicort Respules). [ Time Frame: 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 time to reach terminal phase half-life.


Secondary Outcome Measures :
  1. Mean modified Patient Satisfaction and Preference Questionnaire (PASAPQ) total score. [ Time Frame: 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.

  2. Mean modified PASAPQ satisfaction score. [ Time Frame: 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.

  3. Mean modified PASAPQ score indicating willingness to continue with the device. [ Time Frame: 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.

  4. Adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: During screening (Visit 1), prior to and following dosing on Day -1 and Day 1 (Visit 2) and Day 7 and Day 8 (Visit 3), and during follow-up on Day 15 (Visit 4). ]
    Adverse events occurring from the time of the subject's parent(s)/legal guardian(s) giving informed consent until the End of Trial/early discontinuation.

  5. Adverse device effects (ADEs) and serious adverse device effects (SADEs). [ Time Frame: During screening (Visit 1), prior to and following dosing on Day -1 and Day 1 (Visit 2) and Day 7 and Day 8 (Visit 3), and during follow-up on Day 15 (Visit 4). ]
    Adverse device effects occurring from the time of the subject's parent(s)/legal guardian(s) giving informed consent until the End of Trial/early discontinuation.

  6. Changes in vital signs. [ Time Frame: During screening (Visit 1) and prior to and 30 minutes after the start of nebulization on Day 1 (Visit 2). ]
    Vital signs measurements consist of systolic and diastolic blood pressure, heart rate, respiratory rate and body temperature. Vital signs should be performed as close as possible to the scheduled time point.

  7. Changes in physical examination findings. [ Time Frame: During screening (Visit 1), and pre-dose (if an AE was ongoing) and post-dose on Day 8 (Visit 3). ]
    Assessments of general appearance, ears, eyes, nose, throat, mouth, neck, thyroid, skin, cardiovascular, respiratory, abdomen, neurological, musculoskeletal, lymph nodes and extremities. Any changes from baseline judged to be clinically significant by the investigator (or medically qualified designee) will be recorded as AEs.

  8. Use of concomitant medications. [ Time Frame: During screening (Visit 1), prior to and following dosing on Day -1 and Day 1 (Visit 2) and Day 7 and Day 8 (Visit 3), and during follow-up on Day 15 (Visit 4). ]
    Concomitant medications will be coded using the World Health Organization Drug Dictionary.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03421730


Contacts
Contact: Gary Burgess, MD +44(0)1249 667700 clinical.enquiries@vectura.com

Locations
United States, Colorado
Vectura Study Site 0003 Recruiting
Colorado Springs, Colorado, United States, 80907
Contact: Elizabeth Soltero         
United States, North Carolina
Vectura Study Site 0002 Recruiting
Raleigh, North Carolina, United States, 27607
Contact: Patti Becherer         
United States, Oklahoma
Vectura Study Site 0001 Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Jennifer McCollum         
Sponsors and Collaborators
Vectura Limited

Responsible Party: Vectura Limited
ClinicalTrials.gov Identifier: NCT03421730     History of Changes
Other Study ID Numbers: VR647/1/002
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vectura Limited:
mild asthma
budesonide
nebulizer
pediatric
pharmacokinetics

Additional relevant MeSH terms:
Asthma
Respiratory Aspiration
Respiratory Sounds
Bronchial Hyperreactivity
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Budesonide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists