Pharmacokinetics, Pharmacodynamics Profile and Tolerance... | NCT03603106

ID	Type	Description	Link
2013-004428-12	EudraCT Number

Pharmacokinetics, Pharmacodynamics Profile and Tolerance... | NCT03603106 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part I (Phase I)	Experimental	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 Drug: Placebo
Part II (Phase IIA)	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
P03277	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacokinetic (PK) Parameter Cmax	Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter T1/2	T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter Cl	Cl = total clearance. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter Vd	Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection

Contacts/Locations Module

Name	Affiliation	Role
Wouter Haazen, MD	SGS Clinical Pharmacology Unit	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Pharmacology unit, SGS Life Science Services		Antwerp		2060	Belgium

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30870257	Derived	Hao J, Bourrinet P, Desche P. Assessment of Pharmacokinetic, Pharmacodynamic Profile, and Tolerance of Gadopiclenol, A New High Relaxivity GBCA, in Healthy Subjects and Patients With Brain Lesions (Phase I/IIa Study). Invest Radiol. 2019 Jul;54(7):396-402. doi: 10.1097/RLI.0000000000000556.

Arm/Group Information

ID	Title	Description
FG000	Part I (Phase I) P03277 0.025 mmol/kg	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.
FG001	Part I (Phase I) P03277 0.05 mmol/kg	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.
FG002	Part I (Phase I) P03277 0.075 mmol/kg	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.
FG003	Part I (Phase I) P03277 0.1 mmol/kg	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.
FG004	Part I (Phase I) P03277 0.2 mmol/kg	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.
FG005	Part I (Phase I) P03277 0.3 mmol/kg	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.
FG006	Part I (Phase I) Placebo	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.
FG007	Part II (Phase IIA) P03277 0.05 mmol/kg	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.
FG008	Part II (Phase IIA) P03277 0.075 mmol/kg	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.
FG009	Part II (Phase IIA) P03277 0.1 mmol/kg	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.
FG010	Part II (Phase IIA) P03277 0.2 mmol/kg	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects FG0046 subjects FG0056 subjects FG00618 subjects FG0073 subjects FG0083 subjects FG0093 subjects FG0103 subjects
COMPLETED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part I (Phase I) P03277 0.025 mmol/kg	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.
BG001	Part I (Phase I) P03277 0.05 mmol/kg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pharmacokinetic (PK) Parameter Cmax

Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.

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).

Posted

Mean

Standard Deviation

µg/mL

From baseline (30 minutes before injection) to 24 hours post-injection

ID	Title	Description
OG000	Part I (Phase I) P03277 0.025 mmol/kg	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.
OG001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part I (Phase I) P03277 0.025 mmol/kg	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abortion induced	Surgical and medical procedures	MedDRA v16.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Injection site pain	General disorders	MedDRA (16.1)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Jing Hao, MD	Guerbet	+33 (0) 1 45 91 50 00		jing.hao@guerbet.com

Intervention Browse Module

ID	Term
C000656634	gadopiclenol
D012965	Sodium Chloride

ID	Term
D002712	Chlorides
D006851	Hydrochloric Acid
D017606	Chlorine Compounds
D007287	Inorganic Chemicals

Title

Denominators

Categories

Title	Measurements
	BG00026.0(22 to 30) BG00125.5(21 to 37) BG00227.5(23 to 40) BG00325.5(23 to 41) BG00423.0(18 to 36) BG00533.5(23 to 42) BG00626.5(19 to 43) BG00740.0(37 to 50) BG00856.0(25 to 57) BG00956.0(53 to 61) BG01053.0(50 to 58) BG01128.0(18 to 61)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0014 BG0023 BG0033 BG0043 BG0053 BG0068 BG0071 BG0082 BG0091 BG0101 BG01132
Male	BG0003 BG0012 BG0023 BG0033 BG004

Weight

Median

Full Range

Title

Denominators

Categories

Title	Measurements
	BG00081.65(52.2 to 87.4) BG00171.60(54.0 to 83.6) BG00265.00(56.4 to 93.0) BG00372.50(62.0 to 99.2) BG00469.30(68.2 to 87.6) BG00572.50(61.6 to 88.6) BG00667.90(56.8 to 89.4) BG00787.20(85.8 to 89.0) BG00880.40(71.2 to 87.4) BG00987.20(82.4 to 102.8) BG01085.80(79.4 to 101.6) BG01172.85(52.2 to 102.8)

Title

Denominators

Categories

Title	Measurements
	OG000248.7± 54.5 OG001524.5± 69.9 OG002698.7± 378.9 OG003992.0± 233.1 OG0042097.6± 572.3 OG0053916.4± 1114.8 OG006370.8± 117.6 OG007618.2± 439.7 OG008701.6± 48.5 OG0091434.9± 651.5

Primary

PK Parameter T1/2

T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration.

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).

Posted

Mean

Standard Deviation

hours

From baseline (30 minutes before injection) to 24 hours post-injection

ID	Title	Description
OG000	Part I (Phase I) P03277 0.025 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG001	Part I (Phase I) P03277 0.05 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG002	Part I (Phase I) P03277 0.075 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG003	Part I (Phase I) P03277 0.1 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG004	Part I (Phase I) P03277 0.2 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG005	Part I (Phase I) P03277 0.3 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG006	Part II (Phase IIA) 0.05 mmol/kg	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.
OG007	Part II (Phase IIA) 0.075 mmol/kg	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.
OG008	Part II (Phase IIA) 0.1 mmol/kg	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.
OG009	Part II (Phase IIA) 0.2 mmol/kg	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.

Units	Counts
Participants	OG0005 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001.65± 0.43 OG0011.50± 0.22 OG0021.58± 0.30 OG003

Primary

PK Parameter Cl

Cl = total clearance. Blood samples were taken to assess the P03277 concentration.

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).

Posted

Mean

Standard Deviation

mL/min

From baseline (30 minutes before injection) to 24 hours post-injection

ID	Title	Description
OG000	Part I (Phase I) P03277 0.025 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG001	Part I (Phase I) P03277 0.05 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG002	Part I (Phase I) P03277 0.075 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG003	Part I (Phase I) P03277 0.1 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG004	Part I (Phase I) P03277 0.2 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG005	Part I (Phase I) P03277 0.3 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG006	Part II (Phase IIA) 0.05 mmol/kg	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.
OG007	Part II (Phase IIA) 0.075 mmol/kg	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.
OG008	Part II (Phase IIA) 0.1 mmol/kg	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.
OG009	Part II (Phase IIA) 0.2 mmol/kg	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.

Units	Counts
Participants	OG0005 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG00091.7± 8.5 OG001100.1± 9.5 OG002106.4± 20.7 OG003

Primary

PK Parameter Vd

Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.

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).

Posted

Mean

Standard Deviation

From baseline (30 minutes before injection) to 24 hours post-injection

ID	Title	Description
OG000	Part I (Phase I) P03277 0.025 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG001	Part I (Phase I) P03277 0.05 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG002	Part I (Phase I) P03277 0.075 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG003	Part I (Phase I) P03277 0.1 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG004	Part I (Phase I) P03277 0.2 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG005	Part I (Phase I) P03277 0.3 mmol/kg	6 subjects received P03277 in one single administration. P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s.
OG006	Part II (Phase IIA) 0.05 mmol/kg	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.
OG007	Part II (Phase IIA) 0.075 mmol/kg	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.
OG008	Part II (Phase IIA) 0.1 mmol/kg	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.
OG009	Part II (Phase IIA) 0.2 mmol/kg	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.

Units	Counts
Participants	OG0005 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG00013203± 4122 OG00112945± 1692 OG00214312± 2742 OG003