Clinical Trial Results:
A Randomized, Double blind, Placebo controlled, Two-Way Crossover 7-day study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Dose Inhaled GW642444 25μg in Children aged 5-11 years with Persistent Asthma
Summary
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EudraCT number |
2012-000741-12 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 Apr 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2016
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First version publication date |
14 May 2015
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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 |
HZA112776
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01453296 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, +1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, +1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000431-PIP01-08 | ||
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 |
27 May 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Apr 2011
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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 |
To determine the safety and tolerability following administration of GW642444 25
μg, via a novel dry powder inhaler, once-daily for 7 days in subjects aged 5–11
years.
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Protection of trial subjects |
A parent was required to stay with the subjects for the long days in the clinic. As much as possible children in the same age group were scheduled for visits on the same day. Games and movies were provided for diversion during the long clinic days. Effort was made to have the same staff members work with the children to help reduce anxiety. Topical anesthetics were used at injection site to reduce discomfort from blood collections. An indwelling cannula was inserted for serial blood draws, to prevent the pain and distress associated with repeated needle sticks.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Mar 2010
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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 |
United States: 28
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Worldwide total number of subjects |
28
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EEA total number of subjects |
0
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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) |
28
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 |
Participants were enrolled into one of two cohorts based upon age; the younger cohort was enrolled after a review of the safety/pharmacokinetic data of at least six participants from the older cohort. Each participant was assigned to treatment randomly; assignment was not to be influenced by whether participants were in Cohort 1 or Cohort 2. | ||||||||||||||||||
Pre-assignment
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Screening details |
A Baseline assessment was carried out on Day 1 of the first treatment period. Participants were then randomized to one of the two possible treatment sequences (Vilanterol [VI] 25 micrograms [µg] followed by matching Placebo; matching placebo followed by VI 25 µg) in a 1:1 ratio in an AB or BA sequence. | ||||||||||||||||||
Period 1
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Period 1 title |
Treatment Period 1 (Overall)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence 1: VI 25 µg followed by Placebo | ||||||||||||||||||
Arm description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day wash out (w/o); crossover
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Arm title
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Sequence 2: Placebo followed by VI 25 µg | ||||||||||||||||||
Arm description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental; placebo | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day w/o; crossover
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Period 2
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Period 2 title |
Washout Period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence 1: VI 25 µg followed by Placebo | ||||||||||||||||||
Arm description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental: placebo | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day w/o; crossover
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Arm title
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Sequence 2: Placebo followed by VI 25 µg | ||||||||||||||||||
Arm description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental: placebo | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day w/o; crossover
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Period 3
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Period 3 title |
Treatment Period 2
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence 1: VI 25 µg followed by Placebo | ||||||||||||||||||
Arm description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental: placebo | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day w/o; crossover
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Arm title
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Sequence 2: Placebo followed by VI 25 µg | ||||||||||||||||||
Arm description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||||||||||||||||||
Arm type |
Experimental: placebo | ||||||||||||||||||
Investigational medicinal product name |
Vilanterol; placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Oral use
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Dosage and administration details |
Vilanterol 25mg or Placebo once daily x 14 days; 7 day w/o; crossover
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Period 1 (Overall)
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Reporting group description |
Participants received either vilanterol (VI) 25 micrograms (µg) or matching placebo in the first of two 14-day treatment periods, followed by a repeat dose of the other therapy (the therapy not received in the first treatment period) in the second 14-day treatment period. Inhaled VI 25 µg or matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sequence 1: VI 25 µg followed by Placebo
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Reporting group description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Reporting group title |
Sequence 2: Placebo followed by VI 25 µg
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Reporting group description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Reporting group title |
Sequence 1: VI 25 µg followed by Placebo
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Reporting group description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Reporting group title |
Sequence 2: Placebo followed by VI 25 µg
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Reporting group description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Reporting group title |
Sequence 1: VI 25 µg followed by Placebo
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Reporting group description |
Participants received vilanterol (VI) 25 micrograms (µg) and matching placebo in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Reporting group title |
Sequence 2: Placebo followed by VI 25 µg
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Reporting group description |
Participants received placebo and VI 25 µg in Treatment Periods 1 and 2, respectively. Inhaled VI 25 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days. | ||
Subject analysis set title |
Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.
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Subject analysis set title |
VI 25 µg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants who received VI 25 µg in one or both of the 14-day treatment periods. Inhaled VI 25 µg was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.
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Subject analysis set title |
VI 25 µg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All participants who received VI 25 µg in one or both of the 14-day treatment periods. Inhaled VI 25 µg was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.
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End point title |
Number of participants with any adverse event (AE) or any serious adverse event (SAE) during the Treatment Period [1] | |||||||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General AE/SAE module for a complete list of AEs and SAEs.
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End point type |
Primary
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End point timeframe |
From the start of study medication until Week 11 (Visit 8)/Early Withdrawal
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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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [2] - All Subjects Population: all participants who received at least one dose of study medication [3] - All Subjects Population: all participants who received at least one dose of study medication |
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No statistical analyses for this end point |
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End point title |
Basophil, eosinophil, lymphocyte, monocyte, total neutrophil, platelet, and white blood cell count values at Day 14 of the respective treatment period [4] | |||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [4] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [5] - All Subjects Population,Only those participants available at the specified time points were analyzed [6] - All Subjects Population,Only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Hemoglobin and mean corpuscle hemoglobin concentration (MCHC) values at Day 14 of the respective treatment period [7] | ||||||||||||||||||
End point description |
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [7] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [8] - All Subjects Population, only those participants available at the specified time points were analyed [9] - All Subjects Population, only those participants available at the specified time points were analyed |
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No statistical analyses for this end point |
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End point title |
Reticulocyte and Red Blood Cell (RBC) values at Day 14 of the respective treatment period [10] | ||||||||||||||||||
End point description |
Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [10] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [11] - All Subjects Population,only those participants available at the specified time points were analyzed [12] - All Subjects Population,only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Hematocrit value at Day 14 of the respective treatment period [13] | |||||||||||||||
End point description |
Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation). Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [13] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [14] - All Subjects Population,only those participants available at the specified time points were analyzed [15] - All Subjects Population,only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Mean Corpuscle Volume (MCV) value at Day 14 of the respective treatment period [16] | |||||||||||||||
End point description |
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [16] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [17] - All Subjects Population,only those participants available at the specified time points were analyzed [18] - All Subjects Population,only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Mean Corpuscle Hemoglobin (MCH) value at Day 14 of the respective treatment period [19] | |||||||||||||||
End point description |
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period . Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [19] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [20] - All Subjects Population,only those participants available at the specified time points were analyzed [21] - All Subjects Population,only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Alanine amino transferase (ALT), alkaline phosphatase (ALP), aspartate amino transferase (AST), and gamma glutamyl transferase (GGT) values at Day 14 of the respective treatment period [22] | ||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
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End point type |
Primary
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End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
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Notes [22] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
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Notes [23] - All Subjects Population,only those participants available at the specified time points were analyzed [24] - All Subjects Population,only those participants available at the specified time points were analyzed |
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No statistical analyses for this end point |
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End point title |
Albumin and total protein values at Day 14 of the respective treatment period [25] | ||||||||||||||||||
End point description |
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
Notes [25] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [26] - All Subjects Population,only those participants available at the specified time points were analyzed [27] - All Subjects Population,only those participants available at the specified time points were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Calcium, chloride, carbon dioxide (CO2) content/bicarbonate, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) values at Day 14 of the respective treatment period [28] | |||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
|||||||||||||||||||||||||||||||||
Notes [28] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Notes [29] - All Subjects Population,only those participants available at the specified time points were analyzed [30] - All Subjects Population,only those participants available at the specified time points were analyzed |
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Total bilirubin, direct bilirubin, creatinine, and uric acid values at Day 14 of the respective treatment period [31] | ||||||||||||||||||||||||
End point description |
Blood samples were collected for the measurement of total bilirubin, direct bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||||||
Notes [31] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [32] - All Subjects Population,only those participants available at the specified time points were analyzed [33] - All Subjects Population,only those participants available at the specified time points were analyzed |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Peak expiratory flow on Day 1, Day 8, and Day 14 of the respective treatment period [34] | ||||||||||||||||||||||||||||||
End point description |
Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||||||||||||
Notes [34] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [35] - All Subjects Population,only those participants available at the specified time points were analyzed [36] - All Subjects Population,only those participants available at the specified time points were analyzed |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Day 1, Day 8, and Day 14 of the respective treatment period [37] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SBP and DBP were measured at Day 1, Day 8, and Day 14 of the respective treatment period. PD=post-dose. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Day 8, and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [37] - 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: No statistical analysis was performed for this primary endpoint; thus, no data are available. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [38] - All Subjects Population,only those participants available at the specified time points were analyzed [39] - All Subjects Population,only those participants available at the specified time points were analyzed |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Maximum heart rate at Day 1 and Day 14 of the respective treatment period | |||||||||||||||||||||
End point description |
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [40] - All Subjects Population,only those participants available at the specified time points were analyzed [41] - All Subjects Population,only those participants available at the specified time points were analyzed |
||||||||||||||||||||||
Statistical analysis title |
Analysis 1 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [42] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
2.5
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.8 | |||||||||||||||||||||
upper limit |
5.7 | |||||||||||||||||||||
Notes [42] - Estimation based analysis. Day 1 maximum HR (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 2 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [43] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.6
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-2.4 | |||||||||||||||||||||
upper limit |
3.7 | |||||||||||||||||||||
Notes [43] - Estimation based analysis. Day 14 maximum HR (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 3 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [44] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Median difference (final values) | |||||||||||||||||||||
Point estimate |
0.5
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-2.6 | |||||||||||||||||||||
upper limit |
3.6 | |||||||||||||||||||||
Notes [44] - Estimation based analysis. Day 14 maximum HR (0-8 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
|
||||||||||||||||||||||
End point title |
Weighted mean heart rate at Day 1 and Day 14 of the respective treatment period | |||||||||||||||||||||
End point description |
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [45] - All Subjects Population,only those participants available at the specified time points were analyzed [46] - All Subjects Population,only those participants available at the specified time points were analyzed |
||||||||||||||||||||||
Statistical analysis title |
Analysis 1 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [47] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
2.5
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.8 | |||||||||||||||||||||
upper limit |
5.7 | |||||||||||||||||||||
Notes [47] - Estimation based analysis. Day 1 weighted HR (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 2 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [48] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.6
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-2.4 | |||||||||||||||||||||
upper limit |
3.7 | |||||||||||||||||||||
Notes [48] - Estimation based analysis. Day 14 weighted HR (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 3 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [49] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.5
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-2.6 | |||||||||||||||||||||
upper limit |
3.6 | |||||||||||||||||||||
Notes [49] - Estimation based analysis. Day 14 weighted HR (0-8 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
|
||||||||||||||||||||||
End point title |
Maximum QTcF at Day 1 and Day 14 of the respective treatment period | |||||||||||||||||||||
End point description |
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia’s formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [50] - All Subjects Population,only those participants available at the specified time points were analyzed [51] - All Subjects Population,only those participants available at the specified time points were analyzed |
||||||||||||||||||||||
Statistical analysis title |
Analysis 1 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [52] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
1
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-4.5 | |||||||||||||||||||||
upper limit |
6.6 | |||||||||||||||||||||
Notes [52] - Estimation based analysis. Day 1 maximum QTcF (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 2 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [53] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
1.6
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-3.2 | |||||||||||||||||||||
upper limit |
6.3 | |||||||||||||||||||||
Notes [53] - Estimation based analysis. Day 14 maximum QTcF (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 3 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [54] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
1.3
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-3 | |||||||||||||||||||||
upper limit |
5.7 | |||||||||||||||||||||
Notes [54] - Estimation based analysis. Day 14 maximum QTcF (0-8 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
|
||||||||||||||||||||||
End point title |
Weighted mean QTcF at Day 1 and Day 14 of the respective treatment period | |||||||||||||||||||||
End point description |
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia’s formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [55] - All Subjects Population,only those participants available at the specified time points were analyzed [56] - All Subjects Population,only those participants available at the specified time points were analyzed |
||||||||||||||||||||||
Statistical analysis title |
Analysis 1 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [57] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
2.01
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-2.59 | |||||||||||||||||||||
upper limit |
6.61 | |||||||||||||||||||||
Notes [57] - Estimation based analysis. Day 1 weighted QTcF (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 2 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [58] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
2.94
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-1.93 | |||||||||||||||||||||
upper limit |
7.81 | |||||||||||||||||||||
Notes [58] - Estimation based analysis. Day 14 weighted QTcF (0-2 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
||||||||||||||||||||||
Statistical analysis title |
Analysis 3 | |||||||||||||||||||||
Comparison groups |
Placebo v VI 25 µg
|
|||||||||||||||||||||
Number of subjects included in analysis |
54
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [59] | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
3.19
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.7 | |||||||||||||||||||||
upper limit |
7.08 | |||||||||||||||||||||
Notes [59] - Estimation based analysis. Day 14 weighted QTcF (0-8 hr). The estimated value represents the treatment difference: VI 25 µg minus placebo. |
|
|||||||||||||
End point title |
AUC(0-t) and AUC(0-8) on Day 14 of the respective treatment period | ||||||||||||
End point description |
Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 8 hours AUC(0-8) of quantifiable concentration of VI on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, 4, 6, and 8 hours post-dose for participants who were >=20 kilograms and pre-dose; 10 min and 30 min post-dose; and 1, 2, and 4 hours post-dose for participants who were <=20 kilograms on Day 14 of the respective treatment period. Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Population. Pharmacokinetic (PK) Population: all participants in the All Subjects Population for whom a PK sample was obtained and analyzee. Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||
|
|||||||||||||
Notes [60] - PK Population:all participants in All Subjects Population for whom a PK sample was obtained/analyzed |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Cmax on Day 14 of the respective treatment period | ||||||||
End point description |
Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, 4, 6, and 8 hours post-dose for participants who were >=20 kilograms and pre-dose; 10 min and 30 min post-dose; and 1, 2, and 4 hours post-dose for participants who were <=20 kilograms on Day 14 of the respective treatment period.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||
|
|||||||||
Notes [61] - PK Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
tmax, t1/2, and t at Day 14 of the respective treatment period | ||||||||||||||
End point description |
tmax is defined as the time to reach the observed maximum concentration, t1/2 is defined as the time required to reduce the plasma concentration to one half its initial value, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, 4, 6, and 8 hours post-dose for participants who were >=20 kilograms and pre-dose; 10 min and 30 min post-dose; and 1, 2, and 4 hours post-dose for participants who were <=20 kilograms on Day 14 of the respective treatment period. PK Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK Population.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||
|
|||||||||||||||
Notes [62] - PK Population. Only those participants available at the specified time points were analyzed (n=X). |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Blood glucose and potassium on Day 14 of the respective treatment period | ||||||||||||||||||||||||||||||||||||
End point description |
Blood glucose and potassium values were measured on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, 4, 6, and 8 hours post-dose for participants who were >=20 kilograms and pre-dose; 10 min and 30 min post-dose; and 1, 2, and 4 hours post-dose for participants who were <=20 kilograms on Day 14 of the respective treatment period. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg. Treatment and period were fitted as fixed effects and participant was fitted as a random effect.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [63] - All Subjects Population,only those participants available at the specified time points were analyzed [64] - All Subjects Population,only those participants available at the specified time points were analyzed |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Average oropharyngeal cross-sectional area on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for the study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Day 1 and Day 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. All Subjects Population. Only those participants available at the specified time point were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [65] - All Subjects Population. Only those participants available at the specified time point were analyzed [66] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Distance of assessment on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters [cm]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. All Subjects Population. Only those participants available at the specified time point were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [67] - All Subjects Population. Only those participants available at the specified time point were analyzed [68] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Oropharyngeal volume on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (centimeters cubed [cm^3]) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. All Subjects Population. Only those participants available at the specified time point were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [69] - All Subjects Population. Only those participants available at the specified time point were analyzed [70] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Average flow rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||||||||
End point description |
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Average flow rate is defined as the average inspiratory flow rate (Liters [L]/min) across the inhalation profile when inhaling across the resistance of the inhaler. PIFR is defined as the Peak Inspiratory Flow Rate (L/min) of the inhalation profile when inhaling across the resistance of the inhaler.The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the average flow rate and PIFR were determined. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [71] - All Subjects Population. Only those participants available at the specified time point were analyzed [72] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Inhalation time on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhalation time is defined as the duration of the inhalation(s) when inhaling across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalation time was determined. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [73] - All Subjects Population. Only those participants available at the specified time point were analyzed [74] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Inhaled volume on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhaled volume is defined as the volume of air (Liters) inhaled during the inhalation across the resistance of the inhaler.
The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalaled volume was determined. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [75] - All Subjects Population. Only those participants available at the specified time point were analyzed [76] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Peak pressure drop on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||
End point description |
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Peak pressure drop is defined as the maximum pressure drop (kilopascal [kPa]) achieved during inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was calculated for each day (Days 1 and 14 of the respective treatment period), and used for subsequent modeling and prediction of dose emission attributes. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [77] - All Subjects Population. Only those participants available at the specified time point were analyzed [78] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Total emitted dose (TED) on Day 1 and Day 14 of the respective treatment period | ||||||||||||||
End point description |
The total emitted dose (TED) is defined as the mass (micrograms) of the nominal dose that passes beyond the throat. The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted total emitted dose. All Subjects Population. Only those participants available at the specified time point were analyzed. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||
|
|||||||||||||||
Notes [79] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Ex-throat dose (ETD) and ETD <2 microns on Day 1 and Day 14 of the respective treatment period | ||||||||||||||||||||
End point description |
The ex-throat dose (ETD) and the “nominal ETD” is the mass (micrograms) of active investigational material that passes beyond the throat, nominal being the mean.The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted ETD and ETD <2 microns.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Day 1 and Day 14 of the respective treatment period (up to Study Day 49)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [80] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
On-treatment adverse events were reported.
|
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Adverse event reporting additional description |
Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
|
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Reporting groups
|
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Reporting group title |
Placebo
|
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Reporting group description |
All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
VI 25 µg
|
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Reporting group description |
All participants who received VI 25µg in one or both of the two 14-day treatment periods. Inhaled VI 25µg was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |