Clinical Trial Results:
A Phase II, global, randomized study to evaluate the efficacy and safety of Danirixin (GSK1325756) co-administered with a standard-of-care antiviral (oseltamivir), in the treatment of adults hospitalized with influenza
Summary
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EudraCT number |
2016-002512-40 |
Trial protocol |
SE ES NL FR |
Global end of trial date |
24 May 2017
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Jun 2018
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First version publication date |
04 May 2018
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Other versions |
v1 |
Version creation reason |
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 |
201023
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
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) |
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 |
27 Oct 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
24 May 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the efficacy of treatment with IV DNX twice daily given with oral oseltamivir compared to oral oseltamivir twice daily on time to clinical response (TTCR)
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Protection of trial subjects |
Not Applicable.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Romania: 1
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
United States: 8
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Worldwide total number of subjects |
10
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EEA total number of subjects |
2
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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) |
4
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From 65 to 84 years |
5
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85 years and over |
1
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Recruitment
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Recruitment details |
This was a randomized study to evaluate the efficacy and safety of Danirixin (DNX) co-administered with a standard-of-care antiviral (oseltamivir [OSV]), in the treatment of adults hospitalized with influenza. The study enrolled participants in 7 centers across 3 countries (Romania,Sweden and United States) and was terminated due to poor enrollment | ||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 14 participants were screened for the study, of which 4 participants were screening failures. 10 participants received study treatment. | ||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (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, Subject | ||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo + OSV | ||||||||||||||||||||
Arm description |
Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 milligram (mg) twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received matching placebo given as a 1-hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour.
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Investigational medicinal product name |
Oseltamivir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
All participants received open-label oral Oseltamivir 75 mg twice daily given as standard of care.
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Arm title
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DNX 15 mg + OSV | ||||||||||||||||||||
Arm description |
Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Oseltamivir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
All participants received open-label oral Oseltamivir 75 mg twice daily given as standard of care.
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Investigational medicinal product name |
Danirixin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received Danirixin 15 mg given as a 1-hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour.
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Arm title
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DNX 50 mg + OSV | ||||||||||||||||||||
Arm description |
Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Danirixin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received Danirixin 50 mg given as a 1-hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour.
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Investigational medicinal product name |
Oseltamivir
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
All participants received open-label oral Oseltamivir 75 mg twice daily given as standard of care.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo + OSV
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Reporting group description |
Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 milligram (mg) twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DNX 15 mg + OSV
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Reporting group description |
Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DNX 50 mg + OSV
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Reporting group description |
Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo + OSV
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Reporting group description |
Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 milligram (mg) twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||
Reporting group title |
DNX 15 mg + OSV
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Reporting group description |
Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||
Reporting group title |
DNX 50 mg + OSV
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Reporting group description |
Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. |
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End point title |
Time to Clinical Response (TTCR) [1] | ||||||||||||||||||||
End point description |
The clinical response was defined as Hospital discharge due to clinical improvement OR normalization of temperature; and oxygen saturation; and respiratory status/heart rate/systolic blood pressure (normalization of 2 out of these 3 parameters). The clinical response based on vital signs/ventilation status required 24-hour confirmation. Considering 2-hour assessment window, the response confirmation period was 22 hours. Kaplan Meier estimates for the median of TTCR was provided. One participant had vital sign resolution at Baseline and was counted as having a clinical response but was not included in the Kaplan Meier Estimates. Influenza Positive Population (IPP) Population comprised of all participants in the Intent to Treat Exposed (ITT-E) Population with influenza infection (positive influenza Polymerase Chain Reaction [PCR] or culture at any time point) confirmed by central lab testing. Only those participants with data available at the indicated time point were analyzed.
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End point type |
Primary
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End point timeframe |
Up to 45 Days
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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: There are no statistical data to report. |
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Notes [2] - IPP Population [3] - IPP Population [4] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to Respiratory Response (TTRR) | ||||||||||||||||||||
End point description |
Time to Respiratory Response was defined as meeting at least one of the following criteria, and maintained for 24 hours: return to pre-morbid oxygen requirement (participants with chronic oxygen use or ventilator support), or return to no requirement of supplemental oxygen, or respiratory rate <=24 per minute (without supplemental oxygen). Kaplan Meier estimates for the median of TTRR for each treatment group was provided. 99999 indicates data is not available, as data could not be calculated due to insufficient number of participants with events. Due to limited data, no TTRR estimate could be calculated for any of the treatment groups.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [5] - IPP Population [6] - IPP Population [7] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to absence of fever | ||||||||||||||||||||
End point description |
Time from first dose of treatment to time to afebrile status (<=36.6 degree celsius-axilla/temporal or <=37.2 degree celsius- oral, or <=37.7 degree celsius-rectal/core, tympanic) was to be evaluated. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [8] - IPP Population. [9] - IPP Population [10] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to improved oxygen saturation | ||||||||||||||||||||
End point description |
Time from first dose of treatment to time of improved oxygen saturation was to be calculated. A participant with a history of chronic hypoxia (without supplemental oxygen) satisfied normalization criteria for oxygen saturation if the value (without supplemental oxygen) is <=2 percent from participant’s historical oxygen saturation Baseline as recorded within 12 months prior to enrollment as documented in the participant’s medical records. This requirement was to be waived for participants with a history of chronic supplemental oxygen requirement who had a Baseline oxygen saturation <95 percent with supplemental oxygen, within 12 months prior to enrollment as documented in the participant’s medical records. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [11] - IPP Population [12] - IPP Population [13] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to improved heart rate | ||||||||||||||||||||
End point description |
Time from first dose of treatment to time of heart rate <=100 beats per minute was to be evaluated. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [14] - IPP Population [15] - IPP Population [16] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to improved systolic blood pressure (SBP) | ||||||||||||||||||||
End point description |
Time from first dose of treatment to time of SBP at >=90 millimeters of mercury (mmHg) was to be evaluated. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [17] - IPP Population [18] - IPP Population [19] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Percentage of participants with clinical response over time | ||||||||||||||||
End point description |
The clinical response was defined as Hospital discharge due to clinical improvement OR normalization of temperature; and oxygen saturation; and respiratory status/heart rate/systolic blood pressure (normalization of 2 out of these 3 parameters). The clinical response based on vital signs/ventilation status required 24-hour confirmation. Considering 2-hour assessment window, the response confirmation period was 22 hours. Percentage of participants with positive clinical response are presented.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [20] - IPP Population [21] - IPP Population [22] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Percentage of participants with improved respiratory status over time | ||||||||||||||||
End point description |
The Respiratory Response was defined as meeting at least one of the following criteria, and maintained for 24 hours: return to pre-morbid oxygen requirement (participants with chronic oxygen use or ventilator support), or return to no requirement of supplemental oxygen, or respiratory rate <=24 per minute (without supplemental oxygen). Percentage of participants with improved respiratory status has been presented.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [23] - IPP Population [24] - IPP Population [25] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Time to improvement of ventilation status | ||||||||||||||||||||
End point description |
Time to improvement of ventilation status was assessed by modality, frequencies and durations of invasive and non-invasive ventilator support, duration of oxygen supplementation. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [26] - IPP Population [27] - IPP Population [28] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of days of stay in the intensive care unit (ICU) | ||||||||||||||||||||
End point description |
Number of days of stay in the ICU over the treatment period and post treatment period was to be recorded. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [29] - IPP Population [30] - IPP Population [31] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of participants requiring ICU admission and readmission | ||||||||||||||||
End point description |
Number of participants requiring ICU admission during treatment period and after post treatment was to be recorded. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [32] - IPP Population [33] - IPP Population [34] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of days of stay in the hospital | ||||||||||||||||||||
End point description |
Number of days of stay in the hospital over treatment period and post treatment period was to be recorded. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [35] - IPP Population [36] - IPP Population [37] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with development of septic shock | ||||||||||||||||
End point description |
Development of septic shock was to be assessed by occurrence of hypotension requiring vasopressive therapy and serum lactate level >2 millimeter (mm) after adequate fluid resuscitation. Number of participants with development of septic shock were planned to be presented. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [38] - IPP Population [39] - IPP Population [40] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of participants used antibiotics for complications of influenza | ||||||||||||||||
End point description |
Complications of influenza such as bacterial pneumonia, pneumothorax, pleural effusion, acute respiratory distress syndrome (ARDS), myositis, encephalitis, myocarditis, and associated antibiotic use was recorded. Number of participants who reqruied use of associated antibiotics for complications of influenza is presented.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [41] - IPP Population [42] - IPP Population [43] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with improvement in ordinal scale of clinical efficacy over time | ||||||||||||||||
End point description |
Number of participants with improvement in ordinal scale of clinical efficacy over time was to be assessed by: death, mechanical vent, in the ICU, non-ICU hospitalization, and hospital discharge. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.
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End point type |
Secondary
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End point timeframe |
Up to 45 Days
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Notes [44] - IPP Population [45] - IPP Population [46] - IPP Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with any non-serious adverse event (AE); any serious AE (SAE); any AEs of special interest (AESIs) | ||||||||||||||||||||||||
End point description |
An AE is 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AESI were considered for analysis. Safety Population comprised of all participants who received at least 1 dose of study treatment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 45 Days
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [47] - Safety Population |
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No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in albumin and total protein | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected to evaluate albumin and total protein at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). 99999 indicates data was not available due to insufficient number of participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 45 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Notes [48] - Safety Population [49] - Safety Population [50] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in white blood cell count (WBC) and absolute neutrophil count (ANC) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected to evaluate WBC and ANC at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). 99999 indicates data was not available due to insufficient number of participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 45 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [51] - Safety Population [52] - Safety Population [53] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Total Bilirubin (T. Bilirubin), creatinine and Direct Bilirubin (D. Bilirubin) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected to evaluate T. Bilirubin, creatinine and D. Bilirubin at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). 99999 indicates data was not available due to insufficient number of participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 45 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [54] - Safety Population [55] - Safety Population [56] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected to evaluate ALT, AST and ALP at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). 99999 indicates data was not available due to insufficient number of participants.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 45 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [57] - Safety Population [58] - Safety Population [59] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of participants with clinically significant abnormality in electrocardiogram (ECG) | ||||||||||||||||
End point description |
Single 12-lead ECGs were obtained at Baseline and on the day of last dose during the study using an ECG machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QT duration corrected for heart rate (QTc). Number of participants with clinically significant abnormality in ECG are presented.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 6 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [60] - Safety Population [61] - Safety Population [62] - Safety Population |
|||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Maximum observed plasma concentration (Cmax) of intravenous (IV) DNX [63] | |||||||||||||||
End point description |
Cmax of IV DNX was to be derived from the Pharmacokinetics (PK) samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose. PK Population comprised of all participants who underwent blood PK sampling during the study and from whom one or more blood concentration was determined. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose
|
|||||||||||||||
Notes [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period. |
||||||||||||||||
|
||||||||||||||||
Notes [64] - PK Population [65] - PK Population |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC [0-t]) of IV DNX [66] | |||||||||||||||
End point description |
AUC (0-t) of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose
|
|||||||||||||||
Notes [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period. |
||||||||||||||||
|
||||||||||||||||
Notes [67] - PK Population [68] - PK Population |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Time to reach Cmax (Tmax) of IV DNX [69] | |||||||||||||||
End point description |
Tmax of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited PK parameters available.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose
|
|||||||||||||||
Notes [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period. |
||||||||||||||||
|
||||||||||||||||
Notes [70] - PK Population [71] - PK Population |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Average concentration (Cavg) of IV DNX [72] | |||||||||||||||
End point description |
Cavg of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose
|
|||||||||||||||
Notes [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period. |
||||||||||||||||
|
||||||||||||||||
Notes [73] - PK Population [74] - PK Population |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45.
|
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Adverse event reporting additional description |
On treatment SAEs and non-serious AEs were reported for the Safety Population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
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Reporting groups
|
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Reporting group title |
Placebo + OSV
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DNX 50 mg + OSV
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DNX 15 mg + OSV
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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. | |||
Interpretation of data is limited by the few participants enrolled prior to termination of the study due to poor recruitment. |