Clinical Trial Results:
A Phase 2a Randomised, Double-Blind, Placebo-Controlled Repeat Dose Trial of the Activity of MDT-637 in Healthy Subjects Challenged with RSV-A (Memphis 37b)
Summary
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EudraCT number |
2012-001107-20 |
Trial protocol |
GB |
Global end of trial date |
09 Apr 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Jul 2016
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First version publication date |
06 Aug 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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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 |
MDT-637-CP-201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Teva: MCD-CS-001 | ||
Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products, R&D Inc
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Sponsor organisation address |
41 Moores Road, Frazer, PA, United States, 19355
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, +1 215-591-3000, ustevatrials@tevapharm.com
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, +1 215-591-3000, ustevatrials@tevapharm.com
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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 |
23 Mar 2015
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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 |
09 Apr 2014
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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 |
The primary efficacy objective and endpoint of the study is to evaluate the antiviral effect (as defined by reduction in AUC of viral load) of aerosolized MDT-637, in a manner which mimics the timing of the infection and potential treatment application in infants and children.
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Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonisation
(ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6), and any applicable national
and local laws and regulations (eg, Code of Federal Regulations Title 21, Parts 50, 54, 56, 312,
and 314; European Union (EU) Directive 2001/20/EC on the approximation of the laws,
regulations, and administrative provisions of the Member States relating to the implementation
of good clinical practice in the conduct of clinical studies on medicinal products for human use).
Information regarding any investigational study centers participating in this study that could not
comply with these standards was documented.
Each investigator was responsible for performing the study in accordance with the protocol, ICH
guidelines, and GCP, and for collecting, recording, and reporting the data accurately and
properly. Agreement of each investigator to conduct and administer this study in accordance with
the protocol was documented in separate study agreements with the sponsor and other forms as
required by national authorities in the country where the study center is located.
Written and/or oral information about the study was provided to all subjects in a language
understandable by the subjects. The information included an adequate explanation of the aims,
methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written
informed consent was obtained from each subject before any study procedures or assessments
were done. It was explained to the subjects that they were free to refuse entry into the study and
were free to withdraw from the study at any time without prejudice to future treatment.
Each subject’s willingness to participate was documented in writing in a consent
form that was signed by the subject with the date of that signature indicated. Each investigator
kept the original consent forms, and copies were given to the subjects.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Oct 2013
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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 Kingdom: 143
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Worldwide total number of subjects |
143
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EEA total number of subjects |
143
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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) |
143
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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 |
- | ||||||||||||
Pre-assignment
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Screening details |
144 healthy volunteers were screened, enrolled, entered quarantine and were inoculated. One subject withdrew after inoculation but before treatment for personal reasons. This subject was not included in listings, summary tables, or analyses because subjects had to be both inoculated and treated for inclusion in any of the analysis populations. | ||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Investigator, Monitor, Subject | ||||||||||||
Blinding implementation details |
Subjects and investigators remained blinded to the treatment assigned during the study, as did the sponsor’s clinical personnel who were blinded until the database was locked for analysis and the treatment assignment revealed. The randomization code list was computer generated according to a randomization specification,
using a permuted block algorithm and including stratification by quarantine. Subjects were randomly assigned to treatment through pre-packing of the study drug.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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MDT-637 BD | ||||||||||||
Arm description |
MDT-637 administered twice a day (BD) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800 and 2000 hours. Placebo administered via the same dry-powder aerosol inhaler at 1400 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses (14 active, 7 placebo) dispensed over 7 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
MDT-637
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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 |
Inhalation use
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Dosage and administration details |
MDT-637 was administered in aerosolized form via a proprietary, hand-held
device: an MDT-637 EP1C Inhaler. Subjects breathed through a commercially available
facemask that was attached to the device. Each dose of MDT-637 was 132 mcg (ex-face mask). Study drug
(active or placebo) was administered by passive/tidal inhalation, delivered in approximately
2 minutes and approximately 32 tidal breaths. All doses were administered within the Quarantine
Unit.
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Arm title
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MDT-637 TDS | ||||||||||||
Arm description |
MDT-637 administered three times a day (TDS) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800, 1400 and 2000 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
MDT-637
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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 |
Inhalation use
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Dosage and administration details |
MDT-637 was administered in aerosolized form via a proprietary, hand-held
device: an MDT-637 EP1C Inhaler. Subjects breathed through a commercially available
facemask that was attached to the device. Each dose of MDT-637 was 132 mcg (ex-face mask). Study drug
(active or placebo) was administered by passive/tidal inhalation, delivered in approximately
2 minutes and approximately 32 tidal breaths. All doses were administered within the Quarantine
Unit.
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Arm title
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Placebo | ||||||||||||
Arm description |
Inhalation grade lactose administered three times a day via dry-powder, aerosol inhaler at 0800, 1400 and 2000 hours. Placebo Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||
Arm type |
Placebo | ||||||||||||
Investigational medicinal product name |
Inhalation grade lactose
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Investigational medicinal product code |
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Other name |
placebo
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Placebo was administered in aerosolized form via a proprietary, hand-held device: an MDT-637 EP1C Inhaler. Subjects breathed through a commercially available
facemask that was attached to the device. Study drug (active or placebo) was administered by passive/tidal inhalation, delivered in approximately
2 minutes and approximately 32 tidal breaths. All doses were administered within the Quarantine Unit.
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Baseline characteristics reporting groups
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Reporting group title |
MDT-637 BD
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Reporting group description |
MDT-637 administered twice a day (BD) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800 and 2000 hours. Placebo administered via the same dry-powder aerosol inhaler at 1400 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses (14 active, 7 placebo) dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MDT-637 TDS
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Reporting group description |
MDT-637 administered three times a day (TDS) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800, 1400 and 2000 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Inhalation grade lactose administered three times a day via dry-powder, aerosol inhaler at 0800, 1400 and 2000 hours. Placebo Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
MDT-637 BD
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Reporting group description |
MDT-637 administered twice a day (BD) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800 and 2000 hours. Placebo administered via the same dry-powder aerosol inhaler at 1400 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses (14 active, 7 placebo) dispensed over 7 days. | ||
Reporting group title |
MDT-637 TDS
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Reporting group description |
MDT-637 administered three times a day (TDS) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800, 1400 and 2000 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||
Reporting group title |
Placebo
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Reporting group description |
Inhalation grade lactose administered three times a day via dry-powder, aerosol inhaler at 0800, 1400 and 2000 hours. Placebo Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||
Subject analysis set title |
ITT-I MDT-637 BD
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Subjects who were randomized to the MDT-637 BD treatment arm and met the criteria for the Intent-to-Treat Infected (ITT-I) population. The Intent-to-Treat Infected population by non-quantitative polymerase chain reaction (non-qPCR) method (ITT-I) was defined as all randomized subjects who received study drug, received challenge virus RSV-A, and provided at least one post-baseline positive non-qPCR result through day 5 post challenge virus administration. It was the primary population for efficacy analysis.
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Subject analysis set title |
ITT-I MDT-637 TDS
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Subjects who were randomized to the MDT-637 TDS treatment arm and met the criteria for the Intent-to-Treat Infected (ITT-I) population. The Intent-to-Treat Infected population by non-quantitative polymerase chain reaction (non-qPCR) method (ITT-I) was defined as all randomized subjects who received study drug, received challenge virus RSV-A, and provided at least one post-baseline positive non-qPCR result through day 5 post challenge virus administration. It was the primary population for efficacy analysis.
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Subject analysis set title |
ITT-I Placebo
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Subjects who were randomized to the Placebo treatment arm and met the criteria for the Intent-to-Treat Infected (ITT-I) population. The Intent-to-Treat Infected population by non-quantitative polymerase chain reaction (non-qPCR) method (ITT-I) was defined as all randomized subjects who received study drug, received challenge virus RSV-A, and provided at least one post-baseline positive non-qPCR result through day 5 post challenge virus administration. It was the primary population for efficacy analysis.
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Subject analysis set title |
PK MDT-637 BD
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The pharmacokinetic population consisted of all ITT-I or ITT-I-qPCR subjects who had sufficient data to calculate the pharmacokinetic parameters.
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Subject analysis set title |
PK MDT-637 TDS
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The pharmacokinetic population consisted of all ITT-I or ITT-I-qPCR subjects who had sufficient data to calculate the pharmacokinetic parameters.
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Subject analysis set title |
PK Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The pharmacokinetic population consisted of all ITT-I or ITT-I-qPCR subjects who had sufficient data to calculate the pharmacokinetic parameters.
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End point title |
Area Under the Curve of Viral Load from Day 2 to Day 12 Post Challenge | ||||||||||||||||
End point description |
Subjects were challenged with RSV-A inoculum on day 0. Viral load was measured by non-quantitative polymerase chain reaction (non-qPCR) on nasal wash which was performed twice daily. AUC of viral load was calculated by a linear trapezoidal summation method using actual sampling times in the calculations.
PFU = plaque-forming units.
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End point type |
Primary
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End point timeframe |
Day 2 to the last day of discharge from quarantine (usually Day 12)
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Statistical analysis title |
AUC of Viral Load: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Since there were 3 pairwise comparisons for the primary endpoint, a fixed-sequence testing procedure was used in the following order:
1. MDT-637 TDS vs. placebo
2. MDT-637 BD vs. placebo
3. MDT-637 TDS vs. MDT-637 BD
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Comparison groups |
ITT-I Placebo v ITT-I MDT-637 TDS
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Number of subjects included in analysis |
66
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6692 [1] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
1.445
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-5.25 | ||||||||||||||||
upper limit |
8.141 | ||||||||||||||||
Notes [1] - Single fixed effect of treatment. Comparison was performed at the 0.05 significance level. |
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Statistical analysis title |
AUC of Viral Load: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Since there were 3 pairwise comparisons for the primary endpoint, a fixed-sequence testing procedure was used in the following order:
1. MDT-637 TDS vs. placebo
2. MDT-637 BD vs. placebo
3. MDT-637 TDS vs. MDT-637 BD
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Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
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Number of subjects included in analysis |
67
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.1566 [2] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
4.775
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1.865 | ||||||||||||||||
upper limit |
11.416 | ||||||||||||||||
Notes [2] - Single fixed effect of treatment. Comparison was performed at the 0.05 significance level. |
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Statistical analysis title |
AUC of Viral Load: MDT-637 TDA to MDT-637-BD | ||||||||||||||||
Statistical analysis description |
Since there were 3 pairwise comparisons for the primary endpoint, a fixed-sequence testing procedure was used in the following order:
1. MDT-637 TDS vs. placebo
2. MDT-637 BD vs. placebo
3. MDT-637 TDS vs. MDT-637 BD
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Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
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Number of subjects included in analysis |
63
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3364 [3] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-3.33
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-10.172 | ||||||||||||||||
upper limit |
3.512 | ||||||||||||||||
Notes [3] - Single fixed effect of treatment. Comparison was performed at the 0.05 significance level. |
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End point title |
Duration of Viral Shedding by Tissue Culture | ||||||||||||||||
End point description |
Duration of virus shedding was calculated as the number of days elapsed from the date of first detection of RSV-A to the date when virus first became undetectable.
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End point type |
Secondary
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End point timeframe |
Day 1 to Day 12
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Statistical analysis title |
Duration Viral Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Duration of Viral Shedding by Tissue Culture
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Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.2139 [4] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-0.6
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1.7 | ||||||||||||||||
upper limit |
0.4 | ||||||||||||||||
Notes [4] - Comparison was performed at the 0.05 significance level. |
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Statistical analysis title |
Duration Viral Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Duration of Viral Shedding by Tissue Culture
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Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
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Number of subjects included in analysis |
61
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.9682 [5] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-0.1
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1 | ||||||||||||||||
upper limit |
1 | ||||||||||||||||
Notes [5] - Comparison was performed at the 0.05 significance level. |
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Statistical analysis title |
Duration Viral Shedding: MDT-637 TDS - MDT-637-BD | ||||||||||||||||
Statistical analysis description |
Duration of Viral Shedding by Tissue Culture
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Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
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Number of subjects included in analysis |
57
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.2396 [6] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-0.6
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.7 | ||||||||||||||||
upper limit |
0.4 | ||||||||||||||||
Notes [6] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Peak Virus Shedding By Tissue Culture | ||||||||||||||||
End point description |
Peak virus shedding was calculated as maximum viral load assessment.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to Day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Peak Virus Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
60
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.8468 [7] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference in LSM | ||||||||||||||||
Point estimate |
0.068
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.631 | ||||||||||||||||
upper limit |
0.767 | ||||||||||||||||
Notes [7] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Peak Virus Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
61
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.8154 [8] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference in LSM | ||||||||||||||||
Point estimate |
-0.082
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.774 | ||||||||||||||||
upper limit |
0.611 | ||||||||||||||||
Notes [8] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Peak Virus Shedding: MDT-637-TDS to MDT-637-BD | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
57
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6785 [9] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference in LSM | ||||||||||||||||
Point estimate |
0.15
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.566 | ||||||||||||||||
upper limit |
0.865 | ||||||||||||||||
Notes [9] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Total Area Under the Curve (AUC) of Virus Shedding by Tissue Culture | ||||||||||||||||
End point description |
AUC of virus shedding post challenge, per day (cumulative endpoint) for day X (where X was from day 2 after the viral challenge through to day 12) was calculated based on tissue culture data by linear trapezoidal summation method.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 2 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
AUC Viral Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Total Area Under the Curve (AUC) of Virus Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
66
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6466 [10] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
0.936
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.103 | ||||||||||||||||
upper limit |
4.974 | ||||||||||||||||
Notes [10] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
AUC Viral Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Total Area Under the Curve (AUC) of Virus Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
67
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6736 [11] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
0.852
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.152 | ||||||||||||||||
upper limit |
4.857 | ||||||||||||||||
Notes [11] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
AUC Viral Shedding: MDT-637 TDS to MDT-637 BD | ||||||||||||||||
Statistical analysis description |
Total Area Under the Curve (AUC) of Virus Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
63
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.9681 [12] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
0.083
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-4.043 | ||||||||||||||||
upper limit |
4.21 | ||||||||||||||||
Notes [12] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Kaplan-Meier Estimates for Time to Peak Shedding by Tissue Culture | ||||||||||||||||
End point description |
Time to peak shedding was calculated as the number of days between time of first detection of RSV-A and time of maximum viral load.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
60
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3619 [13] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [13] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
61
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7184 [14] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [14] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 TDS to MDT-637-BD | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
57
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.1851 [15] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [15] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding by Tissue Culture | ||||||||||||||||
End point description |
Time to resolution from peak viral shedding was calculated as number of days between time of maximum viral load and first time when virus became undetectable.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
60
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3896 [16] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [16] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
61
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7798 [17] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [17] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 TDS to MDT-637 BD | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding by Tissue Culture
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
57
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.5583 [18] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [18] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Duration of Virus Shedding By Quantitative Polymerase Chain Reaction Assay | ||||||||||||||||
End point description |
Duration of virus shedding was calculated as the number of days elapsed from the date of first detection of RSV-A to the date when virus first became undetectable.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Duration Viral Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Duration of Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
65
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.5931 [19] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-1.23
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-5.78 | ||||||||||||||||
upper limit |
3.32 | ||||||||||||||||
Notes [19] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Duration Viral Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Duration of Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
66
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6436 [20] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
1.06
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.46 | ||||||||||||||||
upper limit |
5.57 | ||||||||||||||||
Notes [20] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Duration Viral Shedding: MDT-637 TDS to MDT-637 BD | ||||||||||||||||
Statistical analysis description |
Duration of Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
63
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3286 [21] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-2.28
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-6.9 | ||||||||||||||||
upper limit |
2.33 | ||||||||||||||||
Notes [21] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Peak Virus Shedding By Quantitative Polymerase Chain Reaction Assay | ||||||||||||||||
End point description |
Peak virus shedding was calculated as maximum viral load assessment.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to Day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Peak Viral Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
65
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7186 [22] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-0.13
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.847 | ||||||||||||||||
upper limit |
0.586 | ||||||||||||||||
Notes [22] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Peak Viral Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
66
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6644 [23] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
0.156
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.555 | ||||||||||||||||
upper limit |
0.866 | ||||||||||||||||
Notes [23] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Peak Viral Shedding: MDT-637 TDS to MDT-637 BD | ||||||||||||||||
Statistical analysis description |
Peak Virus Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
63
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.4364 [24] | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Parameter type |
Difference of LSM | ||||||||||||||||
Point estimate |
-0.286
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.013 | ||||||||||||||||
upper limit |
0.441 | ||||||||||||||||
Notes [24] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Kaplan-Meier Estimates for Time to Peak Shedding By Quantitative Polymerase Chain Reaction Assay | ||||||||||||||||
End point description |
Time to peak virus shedding from the nasal mucosa was calculated as the number of days between time of first detection of RSV-A and time of maximum viral load.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
65
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.2303 [25] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [25] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
66
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7188 [26] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [26] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Peak Shedding: MDT-637 TDS to MDT-637-BD | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Peak Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
63
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.4078 [27] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [27] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||
End point title |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding By Quantitative Polymerase Chain Reaction Assay | ||||||||||||||||
End point description |
Time to resolution from peak viral shedding was calculated as the number of days between time of maximum viral load and first time when virus became undetectable.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 28
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 TDS to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 TDS v ITT-I Placebo
|
||||||||||||||||
Number of subjects included in analysis |
65
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.9607 [28] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [28] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 BD to Placebo | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I Placebo v ITT-I MDT-637 BD
|
||||||||||||||||
Number of subjects included in analysis |
66
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3501 [29] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [29] - Comparison was performed at the 0.05 significance level. |
|||||||||||||||||
Statistical analysis title |
Time to Resolve: MDT-637 TDS to MDT-637 BD | ||||||||||||||||
Statistical analysis description |
Kaplan-Meier Estimates for Time to Resolution from Peak Viral Shedding By Quantitative Polymerase Chain Reaction Assay
|
||||||||||||||||
Comparison groups |
ITT-I MDT-637 BD v ITT-I MDT-637 TDS
|
||||||||||||||||
Number of subjects included in analysis |
63
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.3238 [30] | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [30] - Comparison was performed at the 0.05 significance level. |
|
|||||||||||||||||||||||||
End point title |
Total Mucus Weight by Study Phase | ||||||||||||||||||||||||
End point description |
Subjects were given pre-weighed packets of paper tissues (handkerchiefs). Subjects stored each tissue used for nose blowing or sneezing in an airtight plastic bag. Bags of used tissues were collected daily (24-hour collection) and new bags were distributed. All paper tissues used by each subject were collected for each 24-hour period throughout the quarantine period, to determine the total weight of mucus produced
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
After viral challenge: Day 1 up to day 5
Dosing phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Total Number of Tissues Used by Study Phase | ||||||||||||||||||||||||
End point description |
Subjects were given pre-weighed packets of paper tissues (handkerchiefs). Subjects stored each tissue used for nose blowing or sneezing in an airtight plastic bag. All paper tissues used by each subject were collected for each 24-hour period throughout the quarantine period, to determine the total weight of mucus produced, and the total number of tissues used.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
After viral challenge: Day 1 up to day 5
Dosing phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Subjects With Grade 2 or Worse Symptoms At Any Day Post Inoculation | ||||||||||||||||
End point description |
Subjects were asked to assess challenge virus-related signs and symptoms, and associated severity at scheduled times throughout the quarantine period, and to record the signs and symptoms in the subject diary card. The symptoms that the subjects were asked to assess were: runny nose, stuffy nose, sneezing, sore throat, earache, malaise (tiredness), cough, shortness of breath, headache, and muscle and/or joint pain. For each symptom, subjects were asked to check
the rating that best described how they felt since completing the last diary card, using the following categories:
Grade 0 indicated no symptoms.
Grade 1 meant symptoms were just noticeable.
Grade 2 symptoms indicated 'It's clearly bothersome from time to time, but it doesn't stop me from participating in activities',
Grade 3 indicated 'It's quite bothersome, most or all of the time, and it stops me from participating in activities'.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Duration of Grade 2 or Worse Symptoms | ||||||||||||||||
End point description |
The duration of Grade 2 or worse symptoms was calculated as number of days elapsed from the date of first occurrence of any Grade >2 symptom to the date of last occurrence of any Grade >2 symptom as recorded by subjects in the Symptom Diary Cards.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Notes [31] - Subjects with grade 2 or worse clinical symptoms [32] - Subjects with grade 2 or worse clinical symptoms [33] - Subjects with grade 2 or worse clinical symptoms |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Subjects With Grade 1 or Worse Symptoms At Any Day During the Dose Phase | ||||||||||||||||
End point description |
Subjects were asked to assess challenge virus-related signs and symptoms, and associated severity at scheduled times throughout the quarantine period, and to record the signs and symptoms in the subject diary card. Symptoms were: runny nose, stuffy nose, sneezing, sore throat, earache, malaise (tiredness), cough, shortness of breath, headache, and muscle and/or joint pain. Ratings since completing the previous card were:
0="I have NO symptoms";
1="Just noticeable";
2="It's clearly bothersome from time to time, but it doesn't stop me from participating in activities";
3="It's quite bothersome, most or all of the time and it stops me from participating in activities".
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Dose phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Grade 1 or Worse of Three Symptom Categories (Upper Respiratory Tract, Lower Respiratory Tract, Systemic Symptoms) At Any Day Post Inoculation | ||||||||||||||||||||||||||||
End point description |
The percentage of subjects with Grade ≥1 symptom score was calculated for upper respiratory tract (URTI) symptoms, lower respiratory tract symptoms and systemic symptoms ( ie, malaise and muscle and/or joint aches). The numerator for the proportion was the number of subjects who experienced URTI (or other category) symptoms at any time during post inoculation. The denominator was the number of subjects with at least one record in the symptom diary card post inoculation. The proportion was then multiplied by 100 to create the percentage.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Time to Peak Symptoms Recorded on the Symptom Diary Card | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Time to peak of each reported symptom was calculated as the number of days between administration of virus inoculum and time when the symptom reached its maximum severity. If the duration of maximum was several days, the earliest occurrence was used in the calculations.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1 to day 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [34] - Population counts for each symptom follow the symptom name. [35] - Population counts for each symptom follow the symptom name. [36] - Population counts for each symptom follow the symptom name. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Subjects with Pyrexia At Any Day Post Inoculation | ||||||||||||||||
End point description |
Pyrexia was defined as a temperature of >37.9°C or two SDs greater than the average of the 3 last non-missing assessments prior to the virus inoculum. A subject was considered to have a febrile illness post-challenge if he/she had any occurrence of a temperature of ≥37.9°C (confirmed by a repeat measurement as ≥37.9°C within 20 to 60 minutes) between day 0 and the last day of receiving study drug.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 0 to day 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Mean Duration of Pyrexia | ||||||||||||||||
End point description |
Mean duration of pyrexia was defined as the number of hours with pyrexia.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 0 to day 12
|
||||||||||||||||
|
|||||||||||||||||
Notes [37] - Subjects with pyrexia [38] - Subjects with pyrexia [39] - Subjects with pyrexia |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Area Under the Curve of Temperature During the Dosing Phase | ||||||||||||||||
End point description |
The AUC of temperature during the dosing phase included all time points and was calculated by a linear trapezoidal method.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Dosing phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Successful Doses As Observed by Study Staff | ||||||||||||||||
End point description |
Treatment compliance was calculated as the number of successful doses taken as observed by study staff taken by the planned number of doses and multiplied by 100%.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Dosing phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||
|
|||||||||||||||||
Notes [40] - Intent to treat population [41] - Intent to treat population [42] - Intent to treat population |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Summary of Adverse Events | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
An adverse event was defined in the protocol as any untoward medical occurrence in a clinical study subject to which study drug (active or placebo) had been administered, including occurrences that were not necessarily caused by or related to that product.
Treatment-emergent AEs are those that started after the first dose of study drug.
AE severity was rated as mild (mild level of discomfort and did not interfere with regular activities), moderate, severe (significant level of discomfort and prevented regular activities) or life-threatening.
The investigator determined whether there was a reasonable possibility of treatment relation.
A serious adverse event was an adverse event that resulted in any of the following outcomes or actions:
Death
Life threatening
Required inpatient hospitalization/prolongation of hospitalization
Resulted in persistent or significant disability/incapacity
Congenital anomaly/birth defect
An other important medical event
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 to day 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [43] - Safety population [44] - Safety population [45] - Safety population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Maximum Observed Plasma Drug Concentration (Cmax) | ||||||||||||||||||||||||
End point description |
Blood samples to determine the pharmacokinetic profile of MDT-637 in plasma of subjects inoculated with RSV-A were taken only in the subjects who participated in quarantine 2, and were linked to the morning dose.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 6 and 12 (dose days 2 and 7): predose (0 hours -15 minutes), 0.5, 1, 2, 3, 4, 6, 12, 12.5, 13, 14, 16, 18, and 24 hours
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [46] - Subjects from quarantine 2 only [47] - Subjects from quarantine 2 only [48] - Placebo-treated subjects do not have MDT-637 PK results reported. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Time To Maximum Observed Drug Concentration (Tmax) | ||||||||||||||||||||||||
End point description |
Blood samples to determine the pharmacokinetic profile of MDT-637 in plasma of subjects inoculated with RSV-A were taken only in the subjects who participated in quarantine 2, and were linked to the morning dose.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 6 and 12 (dose days 2 and 7): predose (0 hours -15 minutes), 0.5, 1, 2, 3, 4, 6, 12, 12.5, 13, 14, 16, 18, and 24 hours
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [49] - Subjects from quarantine 2 only [50] - Subjects from quarantine 2 only [51] - Placebo-treated subjects do not have MDT-637 PK results reported. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Area Under The Plasma-Concentration-Time Curve From Time 0 To The Time Of The Last Measurable Drug Concentration (AUC0-t) | ||||||||||||||||||||||||
End point description |
Blood samples to determine the pharmacokinetic profile of MDT-637 in plasma of subjects inoculated with RSV-A were taken only in the subjects who participated in quarantine 2, and were linked to the morning dose.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 6 and 12 (dose days 2 and 7): predose (0 hours -15 minutes), 0.5, 1, 2, 3, 4, 6, 12, 12.5, 13, 14, 16, 18, and 24 hours
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [52] - Subjects from quarantine 2 only [53] - Subjects from quarantine 2 only [54] - Placebo-treated subjects do not have MDT-637 PK results reported. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) | ||||||||||||||||||||||||
End point description |
Blood samples to determine the pharmacokinetic profile of MDT-637 in plasma of subjects inoculated with RSV-A were taken only in the subjects who participated in quarantine 2, and were linked to the morning dose.
Results are not reported because different dosing schedules and the same sampling times for the two MDT treatments meant that results for derived pharmacokinetic variables would not be comparable.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 6 and 12 (dose days 2 and 7): predose (0 hours -15 minutes), 0.5, 1, 2, 3, 4, 6, 12, 12.5, 13, 14, 16, 18, and 24 hours
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [55] - Different dosing schedules for the two MDT arms meant results for derived PK were not comparable. [56] - Different dosing schedules for the two MDT arms meant results for derived PK were not comparable. [57] - Placebo-treated subjects do not have MDT-637 PK results reported. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Elimination half life (t½) | ||||||||||||||||||||||||
End point description |
Blood samples to determine the pharmacokinetic profile of MDT-637 in plasma of subjects inoculated
with RSV-A were taken only in the subjects who participated in quarantine 2, and were linked to the
morning dose.
Results are not reported because different dosing schedules and the same sampling times for the two
MDT treatments meant that results for derived pharmacokinetic variables would not be comparable.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Days 6 and 12 (dose days 2 and 7): predose (0 hours -15 minutes), 0.5, 1, 2, 3, 4, 6, 12, 12.5, 13, 14, 16, 18, and 24 hours
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [58] - Different dosing schedules for the two MDT arms meant results for derived PK were not comparable [59] - Different dosing schedules for the two MDT arms meant results for derived PK were not comparable [60] - Placebo-treated subjects do not have MDT-637 PK results reported. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Dosing phase: When PRC positive or Day 5 at latest, to Day 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The symptoms that were recorded on the diary cards were presumed to represent challenge virus infection consequent to challenge, and were not to be captured as adverse events unless they met one of the criteria for a serious adverse event. However, this was not followed consistently as there were no SAEs but there were TEAEs with those symptoms.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MDT-637 BD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
MDT-637 administered twice a day (BD) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800 and 2000 hours. Placebo administered via the same dry-powder aerosol inhaler at 1400 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses (14 active, 7 placebo) dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MDT-637 TDS
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
MDT-637 administered three times a day (TDS) via dry-powder, aerosol inhaler at a dose of approximately 132 mcg with daily administration at 0800, 1400 and 2000 hours. Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Inhalation grade lactose administered three times a day via dry-powder, aerosol inhaler at 0800, 1400 and 2000 hours. Placebo Dosing commenced on Days 2, 3, 4 or 5, post-inoculum dependent on a positive non-qPCR nasal wash result for the presence of the challenge virus. The total dose was up to 21 consecutive doses dispensed over 7 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
10 Jul 2013 |
Amendment 1 (dated 10 July 2013) to the protocol was issued before any subjects were enrolled into the study.
The following major procedural changes (not all-inclusive) were made to the protocol:
- The following secondary objectives were added: antiviral effect (as defined by reduction in log AUC viral load by TCID50), and performance and safety of the inhaler device.
- The inclusion and exclusion criteria were clarified
- The study procedures were clarified |
||
11 Sep 2013 |
Amendment 2 (dated 11 September 2013) to the protocol was issued after screening had started but before any subjects entered quarantine.
The following major procedural changes (not all-inclusive) were made to the protocol:
- The BD dosing regimen was added
- Further information was added on the background to the product, the use of the facemask and device, risk-benefit assessment, and definitions and reporting requirements of any adverse reactions to the EP1C inhaler device.
- The sponsor was changed from MicroDose to Teva, which resulted in a change of pharmacovigilance reporting procedures. |
||
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 |