CompletedNCT03657264Updated Jul 18, 2022Results posted

Cardiac Safety Evaluation of P03277

A Phase 1 interventional study of P03277 0.1 mmol/kg and Moxifloxacin 400mg in Healthy Volunteers, sponsored by Guerbet. Completed at 1 site in Belgium. Open to participants aged 18 Years to 59 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-07-18.

Sponsored by Guerbet · Phase 1, Interventional, and Diagnostic

From the registry’s dates

Registered 1 year after the study started (first participant enrolled Aug 2017, registered Aug 2018).

Phase: Phase 1
Study type: Interventional
Enrollment: 48
Allocation: Randomized
Ages: 18 Years to 59 Years
Sex: All

Study summary

The study is a Phase I, Single center, Randomized, Cross-over Double-blind Placebo-controlled and Open-label Positive-controlled (moxifloxacin) in healthy volunteers.

The primary objective is to assess the cardiac safety after administration of P03277 to 48 healthy volunteers at dose of 0.1 mmol/kg (anticipated clinical dose) and 0.3 mmol/kg (supra-clinical dose) by evaluating the QT and QTc intervals.

Read the detailed description

Each subjects will be administered with 4 products (P03277 at the 2 different doses, placebo and moxifloxacin) in a 4*4 cross over sequence balanced for first order carry over effect. Twelve subjects will be assigned to each sequence (6 males and 6 females). The volunteers will be enrolled sequentially by cohort of 8 subjects.

ECG measurements will be compared with ECG parameters collected after administration of placebo (Nacl 0.9%). The test sensitivity will be assessed using a positive control (moxifloxacin 400 mg per os) known to induce delays in QT intervals.

Conditions studied

Healthy Volunteers

Keywords

Gadolinium-based contrast agent
Cardiac safety
ECG
Gadopiclenol

In context

Lead sponsor

Guerbet is the lead sponsor of 42 studies on the registry; 2 are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.

Browse Guerbet studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 59 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Subject assessed as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)
Subject with a Body Mass Index (BMI) > 19 kg/m² and \< 28 kg/m² and a weight at least of 40 kg for female and 50 kg for male and at maximum of 100 kg

Exclusion criteria

Exclusion Criteria:

Study design

Phase: Phase 1
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 48 participants (actual)

Study arms

Experimental
Sequence 1
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).
Drug: P03277 0.1 mmol/kg · Drug: Moxifloxacin 400mg · Drug: NaCl 0.9% · Drug: P03277 0.3 mmol/kg
Experimental
Sequence 2
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).
Drug: P03277 0.1 mmol/kg · Drug: Moxifloxacin 400mg · Drug: NaCl 0.9% · Drug: P03277 0.3 mmol/kg
Experimental
Sequence 3
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).
Drug: P03277 0.1 mmol/kg · Drug: Moxifloxacin 400mg · Drug: NaCl 0.9% · Drug: P03277 0.3 mmol/kg
Experimental
Sequence 4
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).
Drug: P03277 0.1 mmol/kg · Drug: Moxifloxacin 400mg · Drug: NaCl 0.9% · Drug: P03277 0.3 mmol/kg

Interventions

DrugP03277 0.1 mmol/kg
Drug page: Gadopiclenol
Single intravenous bolus injection at 2 mL/sec
Also known as: Gadopiclenol
DrugMoxifloxacin 400mg
One tablet per os
DrugNaCl 0.9%
Single intravenous bolus injection at 2 mL/sec
DrugP03277 0.3 mmol/kg
Drug page: Gadopiclenol
Single intravenous bolus injection at 2 mL/sec
Also known as: Gadopiclenol

What researchers measure

Primary outcomes

Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
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.

Secondary outcomes

Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
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.
Predicted Value of ∆∆QTc at Cmax
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.

Results

Posted Aug 22, 2019

Participant flow

Participant flow — Overall Study
Milestone	Sequence 1	Sequence 2	Sequence 3	Sequence 4
Started	12	12	12	12
Completed	12	12	12	12
Not completed	0	0	0	0

Outcome measures

PrimaryChange-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)

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.
Reported as:: Least squares mean · milliseconds

Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
milliseconds	P03277 0.1 mmol/kg	P03277 0.3 mmol/kg	Placebo
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

Statistical analysis

P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.73 · 90% CI -1.23 to 2.69Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.48 · 90% CI -1.32 to 2.29Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.16 · 90% CI -1.76 to 2.08Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.63 · 90% CI -1.09 to 2.35Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.18 · 90% CI -1.88 to 2.25Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.45 · 90% CI -1.47 to 2.37Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -0.03 · 90% CI -1.99 to 1.92Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 2.39 · 90% CI 0.35 to 4.43Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.27 · 90% CI -1.57 to 2.12Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 1.11 · 90% CI -1.15 to 3.37Each timepoint was tested through a separate model.
P03277 0.1 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.31 · 90% CI -1.52 to 2.14Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 4.81 · 90% CI 2.84 to 6.78Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 1.93 · 90% CI 0.12 to 3.73Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.20 · 90% CI -1.71 to 2.12Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.43 · 90% CI -1.29 to 2.15Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.47 · 90% CI -1.60 to 2.53Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -1.11 · 90% CI -3.03 to 0.81Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -1.17 · 90% CI -3.13 to 0.78Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -1.33 · 90% CI -3.36 to 0.71Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -0.85 · 90% CI -2.69 to 1.00Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: -1.94 · 90% CI -4.19 to 0.32Each timepoint was tested through a separate model.
P03277 0.3 mmol/kg vs Placebo · ANCOVA · Least squares mean difference: 0.21 · 90% CI -1.62 to 2.04Each timepoint was tested through a separate model.

SecondaryChange-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)

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.
Reported as:: Least squares mean · milliseconds

Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)
milliseconds	Positive Control (Moxifloxacin)	Placebo
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

Statistical analysis

Positive Control (Moxifloxacin) vs Placebo · ANCOVA · Least squares mean difference: 4.62 · 90% CI 2.58 to 6.66As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Positive Control (Moxifloxacin) vs Placebo · ANCOVA · Least squares mean difference: 9.40 · 90% CI 7.14 to 11.66As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Positive Control (Moxifloxacin) vs Placebo · ANCOVA · Least squares mean difference: 10.55 · 90% CI 7.92 to 13.17As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Positive Control (Moxifloxacin) vs Placebo · ANCOVA · Least squares mean difference: 10.33 · 90% CI 7.70 to 12.95As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.
Positive Control (Moxifloxacin) vs Placebo · ANCOVA · Least squares mean difference: 10.65 · 90% CI 8.05 to 13.25As multiple timepoints were examined separately, the overall type I error rate needed to be adjusted.

SecondaryPredicted Value of ∆∆QTc at Cmax

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.
Reported as:: Number · milliseconds

Predicted Value of ∆∆QTc at Cmax
milliseconds	P03277 0.1 mmol/kg	P03277 0.3 mmol/kg
Predicted Value of ∆∆QTc at Cmax	0.41 (-0.08 to 0.90)	2.23 (1.19 to 3.26)

Adverse events

Collected over From informed consent signature until the end of the confinement period, i.e. a period ranging from 32 to 41 days.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
P03277 0.1 mmol/kg	0/48 (0%)	0/48 (0%)	25/48 (52.1%)
P03277 0.3 mmol/kg	0/48 (0%)	0/48 (0%)	22/48 (45.8%)
Positive Control (Moxifloxacin)	0/48 (0%)	0/48 (0%)	16/48 (33.3%)
Placebo	0/48 (0%)	0/48 (0%)	22/48 (45.8%)

Most frequent other events

Showing 10 of 38

Most frequent other events
Event	P03277 0.1 mmol/kg	P03277 0.3 mmol/kg	Positive Control (Moxifloxacin)	Placebo
Application site irritationGeneral disorders	6/48	7/48	5/48	6/48
HeadacheNervous system disorders	6/48	5/48	4/48	4/48
Injection site haematomaGeneral disorders	4/48	3/48	0/48	1/48
Injection site painGeneral disorders	2/48	0/48	0/48	4/48
DiarrhoeaGastrointestinal disorders	0/48	1/48	3/48	2/48
Injection site erythemaGeneral disorders	2/48	1/48	0/48	1/48
DysgeusiaNervous system disorders	1/48	1/48	0/48	2/48
DizzinessNervous system disorders	1/48	0/48	2/48	0/48
NauseaGastrointestinal disorders	0/48	2/48	0/48	1/48
Back painMusculoskeletal and connective tissue disorders	0/48	2/48	0/48	0/48

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Total
Mean	35.8 ± 13.5	41.9 ± 11.1	44.8 ± 11.1	39.8 ± 10.2	40.5 ± 11.6

Sex: Female, Male
Sex: Female, Male(Participants)	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Total
Female	6	6	6	6	24
Male	6	6	6	6	24

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	1	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	0	0	0
White	11	12	12	12	47
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Weight
Weight(kg)	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Total
Mean	76.3 ± 10.4	77.6 ± 11.1	75.9 ± 8.3	71.3 ± 9.8	75.3 ± 9.9

Study locations

1 site

Clinical Pharmacology unit, SGS-Life Science Service
Antwerp, 2060, Belgium

References and documents

Study documents

Study protocol · Aug 31, 2018
Statistical analysis plan · Jul 24, 2018

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 18, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03657264
Lead sponsor: Guerbet
Responsible party: Sponsor
First posted: Sep 5, 2018
Start date: Aug 21, 2017
Primary completion: Jun 7, 2018
Completion: Jun 7, 2018
Results posted: Aug 22, 2019
Last update: Jul 18, 2022

Study contacts

Frederic Vanhoutte, MD

principal investigator · SGS Clinical Pharmacology Unit

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Gadopiclenol

Other studies from this sponsor

Guerbet →

Start the discussion