Healthy VolunteersPhase 1/2NCT03603106

Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions

A Phase 1/2 study testing P03277 in people with Healthy Volunteers and Brain Lesion, run by Guerbet at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, Brain Lesion
What is being tested?: P03277
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 142 participants
Where: 1 siteBelgium
Study dates: 25 Nov 2013to 17 Apr 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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).

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

Clinical Pharmacology unit, SGS Life Science Services
Antwerp, 2060

Other trials in Belgium

About this study

Official title: Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions

Read the 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.

Conditions: Healthy Volunteers, Brain Lesion
Being tested: P03277, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

P03277Drug
Also called Gadopiclenol
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.
PlaceboDrug
Also called NaCl 0.9%
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.

Study groups in NCT03603106
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: P03277

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetic (PK) Parameter Cmax
Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline (30 minutes before injection) to 24 hours post-injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Nov 201317 Apr 2015

First posted27 Jul 2018
Study start25 Nov 2013
Primary completion17 Apr 2015
Study completion17 Apr 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Sequential
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.
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 142 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03603106
Sponsor's protocol ID: GDX-44-003
Other IDs: 2013-004428-12
Status last verified: May 2021
First submitted: 16 Jul 2018
Last updated: 14 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 30870257

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
ClinicalTrials.gov ID: NCT03603106
Acronym / sponsor ID: GDX-44-003
Conditions: Healthy Volunteers, Brain Lesion
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 142 participants (actual)
Lead sponsor: GuerbetIndustry (pharma, biotech, devices)
Study start: 25 Nov 2013 (actual)
Primary completion: 17 Apr 2015 (actual)
Study completion: 17 Apr 2015 (actual)
First posted: 27 Jul 2018 (actual)
Results: Posted 12 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Sequential
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
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.

Arm	Type	Receives
Part I (Phase I)	Experimental	Drug: P03277, Drug: PlaceboIn 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.
Part II (Phase IIA)	Experimental	Drug: P03277In each dose group (0.05, 0.075, 0.1 and 0.2 mmol/kg), all 3 patients received one single intravenous administration of P03277.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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).

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
P03277Also: GadopiclenolPart 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.	Drug	Part I (Phase I), Part II (Phase IIA)
PlaceboAlso: NaCl 0.9%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.	Drug	Part I (Phase I)

Primary outcome

Pharmacokinetic (PK) Parameter Cmax
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From baseline (30 minutes before injection) to 24 hours post-injection
Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.

Results and safety

Results posted to the registry on 12 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part I (Phase I) P03277 0.025 mmol/kg	6	6
Part I (Phase I) P03277 0.05 mmol/kg	6	6
Part I (Phase I) P03277 0.075 mmol/kg	6	6
Part I (Phase I) P03277 0.1 mmol/kg	6	6
Part I (Phase I) P03277 0.2 mmol/kg	6	6
Part I (Phase I) P03277 0.3 mmol/kg	6	6
Part I (Phase I) Placebo	18	18
Part II (Phase IIA) P03277 0.05 mmol/kg	3	3
Part II (Phase IIA) P03277 0.075 mmol/kg	3	3
Part II (Phase IIA) P03277 0.1 mmol/kg	3	3
Part II (Phase IIA) P03277 0.2 mmol/kg	3	3

Primary outcome: Pharmacokinetic (PK) Parameter Cmax

Time frame: From baseline (30 minutes before injection) to 24 hours post-injection. Mean (Standard Deviation). Unit: µg/mL

Measure	Part I (Phase I) P03277 0.025 mmol/kg n = 5	Part I (Phase I) P03277 0.05 mmol/kg n = 6	Part I (Phase I) P03277 0.075 mmol/kg n = 6	Part I (Phase I) P03277 0.1 mmol/kg n = 6	Part I (Phase I) P03277 0.2 mmol/kg n = 6	Part I (Phase I) P03277 0.3 mmol/kg n = 6	Part II (Phase IIA) 0.05 mmol/kg n = 3	Part II (Phase IIA) 0.075 mmol/kg n = 3	Part II (Phase IIA) 0.1 mmol/kg n = 2	Part II (Phase IIA) 0.2 mmol/kg n = 3
Value	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)

Population analysed: 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).

Primary outcome: PK Parameter T1/2

Time frame: From baseline (30 minutes before injection) to 24 hours post-injection. Mean (Standard Deviation). Unit: hours

Measure	Part I (Phase I) P03277 0.025 mmol/kg n = 5	Part I (Phase I) P03277 0.05 mmol/kg n = 6	Part I (Phase I) P03277 0.075 mmol/kg n = 6	Part I (Phase I) P03277 0.1 mmol/kg n = 6	Part I (Phase I) P03277 0.2 mmol/kg n = 6	Part I (Phase I) P03277 0.3 mmol/kg n = 6	Part II (Phase IIA) 0.05 mmol/kg n = 3	Part II (Phase IIA) 0.075 mmol/kg n = 3	Part II (Phase IIA) 0.1 mmol/kg n = 2	Part II (Phase IIA) 0.2 mmol/kg n = 3
Value	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)

Primary outcome: PK Parameter Cl

Time frame: From baseline (30 minutes before injection) to 24 hours post-injection. Mean (Standard Deviation). Unit: mL/min

Measure	Part I (Phase I) P03277 0.025 mmol/kg n = 5	Part I (Phase I) P03277 0.05 mmol/kg n = 6	Part I (Phase I) P03277 0.075 mmol/kg n = 6	Part I (Phase I) P03277 0.1 mmol/kg n = 6	Part I (Phase I) P03277 0.2 mmol/kg n = 6	Part I (Phase I) P03277 0.3 mmol/kg n = 6	Part II (Phase IIA) 0.05 mmol/kg n = 3	Part II (Phase IIA) 0.075 mmol/kg n = 3	Part II (Phase IIA) 0.1 mmol/kg n = 2	Part II (Phase IIA) 0.2 mmol/kg n = 3
Value	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)

Primary outcome: PK Parameter Vd

Time frame: From baseline (30 minutes before injection) to 24 hours post-injection. Mean (Standard Deviation). Unit: mL

Measure	Part I (Phase I) P03277 0.025 mmol/kg n = 5	Part I (Phase I) P03277 0.05 mmol/kg n = 6	Part I (Phase I) P03277 0.075 mmol/kg n = 6	Part I (Phase I) P03277 0.1 mmol/kg n = 6	Part I (Phase I) P03277 0.2 mmol/kg n = 6	Part I (Phase I) P03277 0.3 mmol/kg n = 6	Part II (Phase IIA) 0.05 mmol/kg n = 3	Part II (Phase IIA) 0.075 mmol/kg n = 3	Part II (Phase IIA) 0.1 mmol/kg n = 2	Part II (Phase IIA) 0.2 mmol/kg n = 3
Value	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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part I (Phase I) P03277 0.025 mmol/kg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part I (Phase I) P03277 0.05 mmol/kg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part I (Phase I) P03277 0.075 mmol/kg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part I (Phase I) P03277 0.1 mmol/kg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part I (Phase I) P03277 0.2 mmol/kg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part I (Phase I) P03277 0.3 mmol/kg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part I (Phase I) Placebo	0 of 18 (0%)	11 of 18 (61.1%)	0 of 18
Part II (Phase IIA) P03277 0.05 mmol/kg	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Part II (Phase IIA) P03277 0.075 mmol/kg	1 of 3 (33.3%)	1 of 3 (33.3%)	0 of 3
Part II (Phase IIA) P03277 0.1 mmol/kg	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Part II (Phase IIA) P03277 0.2 mmol/kg	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30870257Hao 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Wouter Haazen, MD principal investigator

SGS Clinical Pharmacology Unit

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing P03277 in people with Healthy Volunteers and Brain Lesion, run by Guerbet at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK) Parameter Cmax (time frame: From baseline (30 minutes before injection) to 24 hours post-injection). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03603106, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2021.