Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiac Safety Evaluation of P03277

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03657264
Recruitment Status : Completed
First Posted : September 5, 2018
Results First Posted : August 22, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Guerbet

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Diagnostic
Condition Healthy Volunteers
Interventions Drug: P03277 0.1 mmol/kg
Drug: Moxifloxacin 400mg
Drug: NaCl 0.9%
Drug: P03277 0.3 mmol/kg
Enrollment 48
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4
Hide Arm/Group Description

The sequence of administration is: P/ScD/PC/CD

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: CD/PC/ScD/P

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: ScD/CD/P/PC

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: PC/P/CD/ScD

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).
Period Title: Overall Study
Started 12 12 12 12
Completed 12 12 12 12
Not Completed 0 0 0 0
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Total
Hide Arm/Group Description

The sequence of administration is: P/ScD/PC/CD

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: CD/PC/ScD/P

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: ScD/CD/P/PC

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).

The sequence of administration is: PC/P/CD/ScD

Where:

  • P = Placebo (Nacl 0.9%)
  • CD = P03277 tested at 0.1 mmol/kg
  • ScD = P03277 tested at 0.3 mmol/kg
  • PC = Positive control (moxifloxacin 400 mg – per os).
Total of all reporting groups
Overall Number of Baseline Participants 12 12 12 12 48
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 12 participants 12 participants 48 participants
35.8  (13.5) 41.9  (11.1) 44.8  (11.1) 39.8  (10.2) 40.5  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 12 participants 48 participants
Female
6
  50.0%
6
  50.0%
6
  50.0%
6
  50.0%
24
  50.0%
Male
6
  50.0%
6
  50.0%
6
  50.0%
6
  50.0%
24
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 12 participants 48 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
11
  91.7%
12
 100.0%
12
 100.0%
12
 100.0%
47
  97.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 12 participants 12 participants 12 participants 12 participants 48 participants
76.3  (10.4) 77.6  (11.1) 75.9  (8.3) 71.3  (9.8) 75.3  (9.9)
1.Primary Outcome
Title Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia’s Formula (∆QTcF)
Hide Description

Each subject was monitored with a 12-lead Holter electrocardiogram (ECG). The study had to show that both 0.1 and 0.3 mmol/kg doses of P03277 do not increase the QT interval corrected by Fridericia formula (QTcF).

The study is successful if the difference between each of the two doses of P03277 and placebo for the largest mean change from baseline for the QTcF is lower than 10 milliseconds. The baseline was defined as the mean of the 3 triplicates ECG measured within 1 hour before each product administration.

Time Frame from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1 hour, 5 min, 10 min, 20 min, 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours, 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was performed using the per protocol set which included subjects who had no major protocol deviations throughout their whole study period.
Arm/Group Title P03277 0.1 mmol/kg P03277 0.3 mmol/kg Placebo
Hide Arm/Group Description:
All subjects who received P03277 at 0.1 mmol/kg.
All subjects who received P03277 at 0.3 mmol/kg.
All subjects who received placebo.
Overall Number of Participants Analyzed 47 47 47
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds
5 min 0.97  (0.88) 5.05  (0.89) 0.24  (0.89)
10 min -0.11  (0.86) 1.34  (0.86) -0.59  (0.86)
20 min -1.25  (0.88) -1.20  (0.88) -1.41  (0.88)
30 min -1.06  (0.79) -1.26  (0.79) -1.69  (0.79)
1 hour -2.72  (0.92) -2.44  (0.92) -2.90  (0.92)
1.5 hours -3.08  (0.89) -4.64  (0.89) -3.53  (0.89)
2 hours -2.08  (0.99) -3.22  (0.99) -2.05  (0.99)
3 hours 2.34  (0.98) -1.38  (0.98) -0.05  (0.98)
4 hours 0.61  (0.97) -0.51  (0.97) 0.33  (0.97)
8 hours -2.55  (1.17) -5.59  (1.17) -3.66  (1.17)
24 hours -3.18  (0.92) -3.28  (0.92) -3.49  (0.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 5 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.73
Confidence Interval (2-Sided) 90%
-1.23 to 2.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 10 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.48
Confidence Interval (2-Sided) 90%
-1.32 to 2.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 20 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 90%
-1.76 to 2.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 30 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.63
Confidence Interval (2-Sided) 90%
-1.09 to 2.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 1 hour
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.18
Confidence Interval (2-Sided) 90%
-1.88 to 2.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.25
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 1.5 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.45
Confidence Interval (2-Sided) 90%
-1.47 to 2.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 2 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 90%
-1.99 to 1.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 3 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 2.39
Confidence Interval (2-Sided) 90%
0.35 to 4.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.23
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 4 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.27
Confidence Interval (2-Sided) 90%
-1.57 to 2.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 8 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.11
Confidence Interval (2-Sided) 90%
-1.15 to 3.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.36
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection P03277 0.1 mmol/kg, Placebo
Comments For the timepoint 24 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.31
Confidence Interval (2-Sided) 90%
-1.52 to 2.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.10
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 5 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 4.81
Confidence Interval (2-Sided) 90%
2.84 to 6.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 10 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.93
Confidence Interval (2-Sided) 90%
0.12 to 3.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 20 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.20
Confidence Interval (2-Sided) 90%
-1.71 to 2.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 30 min
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.43
Confidence Interval (2-Sided) 90%
-1.29 to 2.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 1 hour
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.47
Confidence Interval (2-Sided) 90%
-1.60 to 2.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.25
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 1.5 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.11
Confidence Interval (2-Sided) 90%
-3.03 to 0.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 2 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.17
Confidence Interval (2-Sided) 90%
-3.13 to 0.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 3 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.33
Confidence Interval (2-Sided) 90%
-3.36 to 0.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.23
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 4 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.85
Confidence Interval (2-Sided) 90%
-2.69 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 8 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.94
Confidence Interval (2-Sided) 90%
-4.19 to 0.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.36
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection P03277 0.3 mmol/kg, Placebo
Comments For the timepoint 24 hours
Type of Statistical Test Non-Inferiority
Comments The upper limit of the 90% confidence interval was expected lower to the margin of 10 milliseconds for all tests.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments Each timepoint was tested through a separate model.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.21
Confidence Interval (2-Sided) 90%
-1.62 to 2.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia’s Formula (∆QTcF)
Hide Description Each subject was monitored with a 12-lead Holter electrocardiogram (ECG). The assay sensitivity was assessed through this outcome. The difference between the positive control (moxifloxacin) and placebo for the largest mean change from baseline for the QTcF had to be greater than 5 milliseconds for at least one time point. The baseline was defined as the mean of the 3 triplicates ECG measured within 1 hour before each product administration.
Time Frame from 1 hour before any administration until 4 hours post-administration at the following timepoints: -1 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of secondary criteria was performed using the full analysis set which included all randomized subjects.
Arm/Group Title Positive Control (Moxifloxacin) Placebo
Hide Arm/Group Description:
All subjects who received moxifloxacin.
All subjects who received placebo.
Overall Number of Participants Analyzed 48 48
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds
1 hour 1.73  (0.91) -2.89  (0.91)
1.5 hours 6.13  (0.88) -3.27  (0.88)
2 hours 8.60  (0.97) -1.95  (0.97)
3 hours 10.50  (0.97) 0.17  (0.97)
4 hours 11.28  (0.95) 0.63  (0.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Positive Control (Moxifloxacin), Placebo
Comments For the timepoint 1 hour
Type of Statistical Test Superiority
Comments The lower limit of the adjusted confidence interval was expected upper to the margin of 5 milliseconds.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 4.62
Confidence Interval (2-Sided) 90%
2.58 to 6.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Positive Control (Moxifloxacin), Placebo
Comments For the timepoint 1.5 hours
Type of Statistical Test Superiority
Comments The lower limit of the adjusted confidence interval was expected upper to the margin of 5 milliseconds.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 9.40
Confidence Interval (2-Sided) 90%
7.14 to 11.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Positive Control (Moxifloxacin), Placebo
Comments For the timepoint 2 hours
Type of Statistical Test Superiority
Comments The lower limit of the adjusted confidence interval was expected upper to the margin of 5 milliseconds.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 10.55
Confidence Interval (2-Sided) 90%
7.92 to 13.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Positive Control (Moxifloxacin), Placebo
Comments For the timepoint 3 hours
Type of Statistical Test Superiority
Comments The lower limit of the adjusted confidence interval was expected upper to the margin of 5 milliseconds.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 10.33
Confidence Interval (2-Sided) 90%
7.70 to 12.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Positive Control (Moxifloxacin), Placebo
Comments For the timepoint 4 hours
Type of Statistical Test Superiority
Comments The lower limit of the adjusted confidence interval was expected upper to the margin of 5 milliseconds.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments p-value is not shown, as this is a non-inferiority study.
Method ANCOVA
Comments As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 10.65
Confidence Interval (2-Sided) 90%
8.05 to 13.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.10
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Predicted Value of ∆∆QTc at Cmax
Hide Description Concentration-response relationship was investigated between ∆QTc and P03277 concentrations using a mixed model approach. Plasma concentration of P03277 was measured at the same timepoints as ECG measurements.
Time Frame from 1 hour before any administration until 24 hours post-administration.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title P03277 0.1 mmol/kg P03277 0.3 mmol/kg
Hide Arm/Group Description:
All subjects who received P03277 at 0.1 mmol/kg.
All subjects who received P03277 at 0.3 mmol/kg.
Overall Number of Participants Analyzed 48 48
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: milliseconds
0.41
(-0.08 to 0.90)
2.23
(1.19 to 3.26)
Time Frame From informed consent signature until the end of the confinement period, i.e. a period ranging from 32 to 41 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title P03277 0.1 mmol/kg P03277 0.3 mmol/kg Positive Control (Moxifloxacin) Placebo
Hide Arm/Group Description All subjects who received P03277 at 0.1 mmol/kg. All subjects who received P03277 at 0.3 mmol/kg. All subjects who received Moxifloxacin. All subjects who received placebo.
All-Cause Mortality
P03277 0.1 mmol/kg P03277 0.3 mmol/kg Positive Control (Moxifloxacin) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/48 (0.00%)      0/48 (0.00%)      0/48 (0.00%)      0/48 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
P03277 0.1 mmol/kg P03277 0.3 mmol/kg Positive Control (Moxifloxacin) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/48 (0.00%)      0/48 (0.00%)      0/48 (0.00%)      0/48 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
P03277 0.1 mmol/kg P03277 0.3 mmol/kg Positive Control (Moxifloxacin) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/48 (52.08%)      22/48 (45.83%)      16/48 (33.33%)      22/48 (45.83%)    
Cardiac disorders         
Palpitations  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Ear and labyrinth disorders         
Ear pain  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Eye disorders         
Conjunctival hyperaemia  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Gastrointestinal disorders         
Diarrhoea  1  0/48 (0.00%)  0 1/48 (2.08%)  1 3/48 (6.25%)  3 2/48 (4.17%)  2
Nausea  1  0/48 (0.00%)  0 2/48 (4.17%)  2 0/48 (0.00%)  0 1/48 (2.08%)  1
Abdominal pain  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Abdominal pain upper  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Aphthous ulcer  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0
Lip dry  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
General disorders         
Application site irritation  1  6/48 (12.50%)  7 7/48 (14.58%)  8 5/48 (10.42%)  5 6/48 (12.50%)  6
Injection site haematoma  1  4/48 (8.33%)  4 3/48 (6.25%)  3 0/48 (0.00%)  0 1/48 (2.08%)  1
Injection site erythema  1  2/48 (4.17%)  2 1/48 (2.08%)  1 0/48 (0.00%)  0 1/48 (2.08%)  1
Catheter site haematoma  1  1/48 (2.08%)  1 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Injection site inflammation  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Injection site rash  1  1/48 (2.08%)  1 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Injection site reaction  1  1/48 (2.08%)  1 0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0
Catheter site erythema  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Catheter site pain  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0
Catheter site related reaction  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Catheter site swelling  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0
Feeling hot  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Influenza like illness  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Injection site discomfort  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0
Injection site extravasation  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Injection site pain  1  2/48 (4.17%)  2 0/48 (0.00%)  0 0/48 (0.00%)  0 4/48 (8.33%)  4
Asthenia  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain  1  0/48 (0.00%)  0 2/48 (4.17%)  2 0/48 (0.00%)  0 0/48 (0.00%)  0
Musculoskeletal stiffness  1  0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1
Nervous system disorders         
Headache  1  6/48 (12.50%)  6 5/48 (10.42%)  6 4/48 (8.33%)  4 4/48 (8.33%)  4
Dysgeusia  1  1/48 (2.08%)  1 1/48 (2.08%)  1 0/48 (0.00%)  0 2/48 (4.17%)  2
Dizziness  1  1/48 (2.08%)  1 0/48 (0.00%)  0 2/48 (4.17%)  2 0/48 (0.00%)  0
Paraesthesia  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0
Psychiatric disorders         
Nightmare  1  1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0 0/48 (0.00%)  0
Reproductive system and breast disorders         
Vulvovaginal discomfort  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal pain  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 1/48 (2.08%)  1
Dyspnoea  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Throat tightness  1  0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0 0/48 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dry skin  1  0/48 (0.00%)  0 0/48 (0.00%)  0 1/48 (2.08%)  1 0/48 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jing Hao, MD
Organization: Guerbet
Phone: +33145915000
EMail: jing.hao@guerbet.com
Layout table for additonal information
Responsible Party: Guerbet
ClinicalTrials.gov Identifier: NCT03657264     History of Changes
Other Study ID Numbers: GDX-44-006
First Submitted: August 31, 2018
First Posted: September 5, 2018
Results First Submitted: March 12, 2019
Results First Posted: August 22, 2019
Last Update Posted: August 22, 2019