Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
Sponsor
Guerbet (Industry)
Overall Status
Completed
CT.gov ID
NCT03603106
Collaborator
(none)
142
1
2
16.7
8.5
Study Details
Study Description
Brief Summary
The primary objective of this study was to evaluate the safety (clinical and biological) and pharmacokinetics (plasma and urine) profile of P03277 following single administration at ascending dose levels in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This single-center, single ascending dose, phase I/IIa study was divided into 2 parts, involving both healthy subjects and patients with brain lesions:
-
Study Part I included healthy subjects: double-blind, randomized, placebo control;
-
Study Part II included patients with brain lesions: open-label.
In Part I, the following 6 dosing groups were investigated:
-
Group 1: 0.025 mmol/kg
-
Group 2: 0.05 mmol/kg
-
Group 3: 0.075 mmol/kg
-
Group 4: 0.1 mmol/kg
-
Group 5: 0.2 mmol/kg
-
Group 6: 0.3 mmol/kg
Healthy subjects were included and were then administered with P03277 or placebo and were to undergo MRI examination according to the randomization scheme.
In Part II, the following 4 doses groups were investigated:
-
Group 7: 0.05 mmol/kg
-
Group 8: 0.075 mmol/kg
-
Group 9: 0.1 mmol/kg
-
Group 10: 0.2 mmol/kg
Patients with brain lesions were included and were then administered with P03277 and underwent MRI examination.
Study Design
Study Type:
Interventional
Actual Enrollment
:
142 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Part I: Sequential administration within each group of healthy subjects was established.
Part II: The administration to patients within the same day was sequential to ensure the well-being of the patients. At least a 1-hour interval between 2 administrations had to be respected.Part I: Sequential administration within each group of healthy subjects was established.
Part II: The administration to patients within the same day was sequential to ensure the well-being of the patients. At least a 1-hour interval between 2 administrations had to be respected.
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Diagnostic
Official Title:
Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
Actual Study Start Date
:
Nov 25, 2013
Actual Primary Completion Date
:
Apr 17, 2015
Actual Study Completion Date
:
Apr 17, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part I (Phase I) In each dose group (0.025, 0.05, 0.075, 0.1, 0.2 and 0.3 mmol/kg), 9 healthy subjects were to be included: 6 subjects received P03277 and 3 subjects received placebo in one single intravenous administration. |
Drug: P03277
Part I: P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
Part II: P03277 was administered intravenously with a flow rate of 2 mL/s.
Other Names:
Drug: Placebo
Part I: Placebo was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
Part II: Placebo was administered intravenously with a flow rate of 2 mL/s.
Other Names:
|
| Experimental: Part II (Phase IIA) In each dose group (0.05, 0.075, 0.1 and 0.2 mmol/kg), all 3 patients received one single intravenous administration of P03277. |
Drug: P03277
Part I: P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
Part II: P03277 was administered intravenously with a flow rate of 2 mL/s.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) Parameter Cmax [From baseline (30 minutes before injection) to 24 hours post-injection]
Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.
- PK Parameter T1/2 [From baseline (30 minutes before injection) to 24 hours post-injection]
T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration.
- PK Parameter Cl [From baseline (30 minutes before injection) to 24 hours post-injection]
Cl = total clearance. Blood samples were taken to assess the P03277 concentration.
- PK Parameter Vd [From baseline (30 minutes before injection) to 24 hours post-injection]
Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Part I: Subjects between 18 and 45 years old (inclusive), with a body mass index (BMI) of 18 to 30 kg/m² (exclusive) and in a good health.
-
Part II: Patients 18 years old and older and having at least one brain lesion with a disruption of the blood brain barrier (BBB) and/or with abnormal vascularity in the brain. This/these lesion(s) must have been detected by previous imaging evaluation (Computed Tomography or MRI).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Pharmacology unit, SGS Life Science Services | Antwerpen | Belgium | 2060 |
Sponsors and Collaborators
- Guerbet
Investigators
- Principal Investigator: Wouter Haazen, MD, SGS Clinical Pharmacology Unit
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Guerbet
ClinicalTrials.gov Identifier:
NCT03603106
Other Study ID Numbers:
- GDX-44-003
- 2013-004428-12
First Posted:
Jul 27, 2018
Last Update Posted:
May 14, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | For part I, all patients who were not randomized were screening failures. For part II, all patients who were not allocated to a dose of P03277 were screening failures. |
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.025 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.3 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 3 healthy subjects per dose group received placebo in one single administration. Placebo was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate of 2 mL/s. |
| Period Title: Overall Study | |||||||||||
| STARTED | 6 | 6 | 6 | 6 | 6 | 6 | 18 | 3 | 3 | 3 | 3 |
| COMPLETED | 6 | 6 | 6 | 6 | 6 | 6 | 18 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.025 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.3 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 3 healthy subjects per dose group received placebo in one single administration. Placebo was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate of 2 mL/s. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 6 | 18 | 3 | 3 | 3 | 3 | 66 |
| Age (years) [Median (Full Range) ] | ||||||||||||
| Median (Full Range) [years] |
26.0
|
25.5
|
27.5
|
25.5
|
23.0
|
33.5
|
26.5
|
40.0
|
56.0
|
56.0
|
53.0
|
28.0
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
3
50%
|
4
66.7%
|
3
50%
|
3
50%
|
3
50%
|
3
50%
|
8
44.4%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
1
33.3%
|
32
48.5%
|
| Male |
3
50%
|
2
33.3%
|
3
50%
|
3
50%
|
3
50%
|
3
50%
|
10
55.6%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
2
66.7%
|
34
51.5%
|
| Weight (kg) [Median (Full Range) ] | ||||||||||||
| Median (Full Range) [kg] |
81.65
|
71.60
|
65.00
|
72.50
|
69.30
|
72.50
|
67.90
|
87.20
|
80.40
|
87.20
|
85.80
|
72.85
|
Outcome Measures
| Title | Pharmacokinetic (PK) Parameter Cmax |
|---|---|
| Description | Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration. |
| Time Frame | From baseline (30 minutes before injection) to 24 hours post-injection |
Outcome Measure Data
| Analysis Population Description |
|---|
| In part I, one patient from the "0.025 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect volume of P03277 injected). In part II, one patient from the "0.1 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect route of administration, high probability of extravasation). |
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part II (Phase IIA) 0.05 mmol/kg | Part II (Phase IIA) 0.075 mmol/kg | Part II (Phase IIA) 0.1 mmol/kg | Part II (Phase IIA) 0.2 mmol/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.025 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.3 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate of 2 mL/s. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 | 3 | 3 | 2 | 3 |
| Mean (Standard Deviation) [µg/mL] |
248.7
(54.5)
|
524.5
(69.9)
|
698.7
(378.9)
|
992.0
(233.1)
|
2097.6
(572.3)
|
3916.4
(1114.8)
|
370.8
(117.6)
|
618.2
(439.7)
|
701.6
(48.5)
|
1434.9
(651.5)
|
| Title | PK Parameter T1/2 |
|---|---|
| Description | T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration. |
| Time Frame | From baseline (30 minutes before injection) to 24 hours post-injection |
Outcome Measure Data
| Analysis Population Description |
|---|
| In part I, one patient from the "0.025 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect volume of P03277 injected). In part II, one patient from the "0.1 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect route of administration, high probability of extravasation). |
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part II (Phase IIA) 0.05 mmol/kg | Part II (Phase IIA) 0.075 mmol/kg | Part II (Phase IIA) 0.1 mmol/kg | Part II (Phase IIA) 0.2 mmol/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 | 3 | 3 | 2 | 3 |
| Mean (Standard Deviation) [hours] |
1.65
(0.43)
|
1.50
(0.22)
|
1.58
(0.30)
|
1.73
(0.26)
|
1.82
(0.35)
|
2.09
(0.15)
|
1.90
(0.04)
|
2.04
(0.06)
|
1.79
(0.17)
|
1.94
(0.06)
|
| Title | PK Parameter Cl |
|---|---|
| Description | Cl = total clearance. Blood samples were taken to assess the P03277 concentration. |
| Time Frame | From baseline (30 minutes before injection) to 24 hours post-injection |
Outcome Measure Data
| Analysis Population Description |
|---|
| In part I, one patient from the "0.025 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect volume of P03277 injected). In part II, one patient from the "0.1 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect route of administration, high probability of extravasation). |
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part II (Phase IIA) 0.05 mmol/kg | Part II (Phase IIA) 0.075 mmol/kg | Part II (Phase IIA) 0.1 mmol/kg | Part II (Phase IIA) 0.2 mmol/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 | 3 | 3 | 2 | 3 |
| Mean (Standard Deviation) [mL/min] |
91.7
(8.5)
|
100.1
(9.5)
|
106.4
(20.7)
|
96.1
(11.8)
|
101.3
(10.9)
|
102.2
(19.0)
|
105.3
(13.5)
|
106.5
(15.7)
|
108.6
(5)
|
109.9
(18.2)
|
| Title | PK Parameter Vd |
|---|---|
| Description | Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration. |
| Time Frame | From baseline (30 minutes before injection) to 24 hours post-injection |
Outcome Measure Data
| Analysis Population Description |
|---|
| In part I, one patient from the "0.025 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect volume of P03277 injected). In part II, one patient from the "0.1 mmol/kg" group was excluded from the pharmacokinetics analysis (incorrect route of administration, high probability of extravasation). |
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part II (Phase IIA) 0.05 mmol/kg | Part II (Phase IIA) 0.075 mmol/kg | Part II (Phase IIA) 0.1 mmol/kg | Part II (Phase IIA) 0.2 mmol/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. | In each dose group, all 3 patients received one single administration of P03277. P03277 was administered intravenously with a flow rate of 2 mL/s. |
| Measure Participants | 5 | 6 | 6 | 6 | 6 | 6 | 3 | 3 | 2 | 3 |
| Mean (Standard Deviation) [mL] |
13203
(4122)
|
12945
(1692)
|
14312
(2742)
|
14351
(2645)
|
15922
(3224)
|
18487
(3575)
|
17320
(1942)
|
18796
(2478)
|
16823
(804)
|
18355
(2522)
|
Adverse Events
| Time Frame | For Part I: adverse events were collected from subjects' enrollment until 7 days after the product (P03277 or placebo) administration. For Part II: adverse events were collected from patients' enrollment until 1 day after P03277 administration. | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All adverse events occuring pre- and post-injection are reported below. | |||||||||||||||||||||
| Arm/Group Title | Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg | |||||||||||
| Arm/Group Description | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.025 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 6 subjects received P03277 in one single administration. P03277 was administered intravenously at 0.3 mmol/kg with a flow rate ranging from 0.5 to 2 mL/s. | 3 healthy subjects per dose group received placebo in one single administration. Placebo was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.05 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.075 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.1 mmol/kg with a flow rate of 2 mL/s. | 3 patients received one single administration of P03277. P03277 was administered intravenously at 0.2 mmol/kg with a flow rate of 2 mL/s. | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/18 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | |||||||||||
| Surgical and medical procedures | ||||||||||||||||||||||
| Abortion induced | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Part I (Phase I) P03277 0.025 mmol/kg | Part I (Phase I) P03277 0.05 mmol/kg | Part I (Phase I) P03277 0.075 mmol/kg | Part I (Phase I) P03277 0.1 mmol/kg | Part I (Phase I) P03277 0.2 mmol/kg | Part I (Phase I) P03277 0.3 mmol/kg | Part I (Phase I) Placebo | Part II (Phase IIA) P03277 0.05 mmol/kg | Part II (Phase IIA) P03277 0.075 mmol/kg | Part II (Phase IIA) P03277 0.1 mmol/kg | Part II (Phase IIA) P03277 0.2 mmol/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 3/6 (50%) | 2/6 (33.3%) | 4/6 (66.7%) | 5/6 (83.3%) | 3/6 (50%) | 11/18 (61.1%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/3 (66.7%) | |||||||||||
| Eye disorders | ||||||||||||||||||||||
| Conjunctivitis | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||
| Abdominal pain | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Diarrhoea | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Nausea | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| General disorders | ||||||||||||||||||||||
| Injection site pain | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 3/18 (16.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Catheter site pain | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Injection site oedema | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Fatigue | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Catheter site dermatitis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Catheter site inflammation | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injection site coldness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injection site erythema | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injection site haematoma | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injection site haemorrhage | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injection site inflammation | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Influenza like illness | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||
| Nasopharyngitis | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Contusion | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Investigations | ||||||||||||||||||||||
| Body temperature increased | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Decreased appetite | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||
| Headache | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 3 | 5/18 (27.8%) | 5 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Dizziness | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Dizziness postural | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||||||
| Pregnancy | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Dysphonia | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Dyspnoea | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Throat irritation | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Sneezing | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Dermatitis contact | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/18 (5.6%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||
| Flushing | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Jing Hao, MD |
|---|---|
| Organization | Guerbet |
| Phone | +33 (0) 1 45 91 50 00 |
| jing.hao@guerbet.com |
Responsible Party:
Guerbet
ClinicalTrials.gov Identifier:
NCT03603106
Other Study ID Numbers:
- GDX-44-003
- 2013-004428-12
First Posted:
Jul 27, 2018
Last Update Posted:
May 14, 2021
Last Verified:
May 1, 2021