Pharmacokinetics, Dialysability and Safety of P03277 in Healthy Volunteers and in Patients With Impaired Renal Function

NCT ID: NCT03657784

Last Updated: 2019-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-13
• Study Completion Date: 2019-08-23

Brief Summary

This is an open-label, non-randomized, successive cohorts design, multicenter, single dose phase I study.

The primary objectives are:

• to evaluate the pharmacokinetics (plasma and urine) profile of P03277 following single intravenous injection (0.1 mmol/kg body weight) in patients with mild to severe renal impairment and in healthy volunteers with normal renal function used as reference.
• to assess dialysability of P03277 following a single intravenous injection (0.1 mmol/kg body weight) in patients with end stage renal disease requiring hemodialysis.

Detailed Description

A full range design including the different degrees of renal impairment and healthy volunteers used as reference has been chosen.

Enrolment will be successive starting with both healthy volunteers (cohort 1) and patients with mild renal impairment (cohort 2), then patients with moderate renal impairment (cohort 3), then patients with severe renal impairment (cohort 4) to end with patients with end stage renal disease (cohort 5). Pharmacokinetics and safety profiles following the confinement period will be reviewed per each successive cohort by a Data Monitoring Committee before starting recruitment of patients in the next cohort. Cohorts 1 and 2 will be recruited in parallel and Data Monitoring Committee review will start after the completion of these first two cohorts.

Conditions

Renal Insufficiency; Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Cohort 1

P03277 will be administered to healthy volunteers with stable normal renal function defined with an absolute value of eGFR ≥ 90 mL/min.

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Cohort 2

P03277 will be administered to patients with stable mild renal impairment defined with an absolute value of eGFR between 60 and 89 mL/min.

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Cohort 3

P03277 will be administered to patients with stable moderate renal impairment defined with an absolute value of eGFR between 30 and 59 mL/min.

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Cohort 4

P03277 will be administered to patients with stable severe renal impairment defined with an absolute value of eGFR between 15 and 29 mL/min.

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Cohort 5

P03277 will be administered to patients with end-stage renal failure who requires 3 hemodialysis sessions per week.

Group Type: EXPERIMENTAL

P03277

Intervention Type: DRUG

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Interventions

P03277

Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Intervention Type: DRUG

Other Intervention Names

gadopiclenol

Eligibility Criteria

Inclusion Criteria

For all subjects:

• Subject being 18 years or older, able and willing to participate in the trial
• Subject in good enough health status as determined by investigator according to medical history, physical examination, vital signs, 12 lead ECG and laboratory tests at screening and inclusion

For healthy volunteers / cohort 1:

Healthy volunteer with stable normal renal function defined with an absolute value of eGFR ≥ 90 mL/min based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements

For patients with renal impairment / cohorts 2 to 5:

• Cohort 2: patient with stable mild renal impairment defined with an absolute value of eGFR between 60 and 89 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements
• Cohort 3: patient with stable moderate renal impairment defined with an absolute value of eGFR between 30 and 59 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements
• Cohort 4: patient with stable severe renal impairment defined with an absolute value of eGFR between 15 and 29 mL/min included based on two eGFR assessments done at screening and inclusion, with a maximum tolerance of 15% between the 2 measurements
• Cohort 5: patient with end-stage renal failure who requires 3 hemodialysis sessions per week

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Guerbet

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Penescu Mircea, MD

Role: PRINCIPAL_INVESTIGATOR

Arensia Phase I unit "Carol Davila" Nephrology Hospital

Locations

Republican Clinical Hospital, Arensia EM Unit

Chisinau, , Moldova

Arensia Phase I unit "Carol Davila" Nephrology Hospital

Bucharest, , Romania

Countries

Moldova; Romania

References

Bradu A, Penescu M, Pitrou C, Hao J, Bourrinet P. Pharmacokinetics, Dialysability, and Safety of Gadopiclenol, a New Gadolinium-Based Contrast Agent, in Patients With Impaired Renal Function. Invest Radiol. 2021 Aug 1;56(8):486-493. doi: 10.1097/RLI.0000000000000764.

Reference Type: DERIVED

PMID: 34197356 (View on PubMed)

Other Identifiers

2017-001211-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GDX-44-005

Identifier Type: -

Identifier Source: org_study_id