Clinical Trial Results:
A clinical study to assess the feasibility of measuring inhaled medication concentrations in exhaled breath condensate obtained from healthy volunteers and asthma patients and to assess the relationship with clinical endpoints
Summary
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EudraCT number |
2017-003177-34 |
Trial protocol |
NL |
Global end of trial date |
20 Aug 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Feb 2022
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First version publication date |
17 Feb 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CHDR1722
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Centre for Human Drug Research
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Sponsor organisation address |
Zernikedreef 8, Leiden, Netherlands, 2333CL
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Public contact |
Principal Investigator, Centre for Human Drug Research, +31 715246400, clintrials@chdr.nl
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Scientific contact |
Principal Investigator, Centre for Human Drug Research, +31 715246400, clintrials@chdr.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Aug 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Aug 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Aug 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary objectives:
• To identify whether EBC can be used as a non-invasive method to measure the PK of salbutamol and tobramycin.
• To determine whether the relationship in mild-moderate asthmatics between pulmonary lung function parameters and salbutamol concentrations can be better described by concentrations in the EBC compared to plasma.
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Protection of trial subjects |
Screening of 12 healthy male volunteers. Measurements: ECG, vitals, pulmonary function tests and bloodsamples for hematological and chemical analysis.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment overall studyperiod | |||||||||||||||
Pre-assignment
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Screening details |
12 healthy male subjects, eligible according to in- and exclusion criteria after screening. | |||||||||||||||
Period 1
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Period 1 title |
Overall studyperiod (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Salbutamol intravenous | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Salbutamol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A total dose of 250 microgram salbutamol (5 ml of 50mcg/ml) will be injected slowly i.v.in 1-10 minutes.
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Arm title
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Salbutamol inhaled | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Salbutamol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A total dose of 400 microgram will be administered using the Volumatic®device.
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Arm title
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Tobramycin intravenous | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tobramycin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
A total dose of 1mg/kg tobramycin will be administered i.v.. For this purpose the required dose of tobramycin 40 mg/ml will be solved in 50-100ml 0.9% Natriumchloride infusion fluid. The infusion will be administered in 30 minutes.
For subjects with a BMI >25the dose will be adjusted for body composition following the following formula:
Dosing weight = Ideal body weight + 0.40 * (Actual body weight –Ideal body weight).
Ideal body weight = length (in meters) * length (in meters) * 25.
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Arm title
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Tobramycin inhaled | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tobramycin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
A total dose of 170 mg tobramycin will be administered by inhalation using the Medix AC2000®nebulizerof Clement Clarke International.
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Baseline characteristics reporting groups
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Reporting group title |
Overall studyperiod
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Reporting group description |
- | ||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Salbutamol intravenous
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Reporting group description |
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Reporting group title |
Salbutamol inhaled
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Reporting group description |
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Reporting group title |
Tobramycin intravenous
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Reporting group description |
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Reporting group title |
Tobramycin inhaled
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Reporting group description |
- |
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End point title |
Treatment-emergent serious adverse events (SAEs) [1] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall studyperiod
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As this was an exploratory study, no formal power analysis was performed. Pharmacokinetic endpoints were summarized descriptively. Please refer to uploaded article. |
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Attachments |
Report |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Overall study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
Studygroup
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Mar 2018 |
The change in this amendment covers the addition of two PK and EBC samples to the protoco |
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08 May 2018 |
additional spirometry measurements with a new spirometrydevice, which we want to validate during stage 2 of the study. |
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28 May 2018 |
-The upper limit for age is increased to 65 years;
- The upper limit for BMI is increased to 35 kg/m2;
- The minimum period subjects have to be off corticosteroid inhalation therapy has been reduced to threeweeks; and,
- For the lung function a post-bronchodilator for FEVI > 70% of predicted will be used instead of pre-bronchodilator FEVr > 70% of predicted. As all asthma subjects will receive salbutamol, either inhaled orintravenously at the start of each the study days, a post bronchodilator lung function is more relevant. lnaddition, exhaled breath condensate sampling involves tidal breathing and is not associated withbronchoconstriction (Baraldi, 2003) . |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |