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

Primary Purpose

Renal Insufficiency, Healthy Volunteers

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

P03277

About this trial

This is an interventional diagnostic trial for Renal Insufficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Republican Clinical Hospital, Arensia EM Unit
Arensia Phase I unit "Carol Davila" Nephrology Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

AUC

AUC: area under the plasma concentration curve. Blood samples will be collected.

Cmax

Cmax: peak concentration. Blood samples will be collected.

t1/2

t1/2: terminal half-life. Blood samples will be collected.

CLT

CLT: total clearance. Blood samples will be collected.

Ae: amount excreted. Urine samples will be collected.

Relative amount of eliminated P03277 in blood

This outcome will be assessed for cohort 5 only. Venous blood samples will be collected at each session of hemodialysis.

Clearance of P03277

This outcome will be assessed for cohort 5 only and at the first hemodialysis only. Arterial and venous blood samples will be collected.

Dialysis clearance of P03277

This outcome will be assessed for cohort 5 only. Venous blood and dialysate samples will be collected at each session of hemodialysis.

Secondary Outcome Measures

P03277concentration in blood (long-term)

Blood samples will be collected.

P03277 concentration in urine (long-term)

Urine samples will be collected.

Full Information

NCT ID

NCT03657784

First Posted

August 31, 2018

Last Updated

October 21, 2019

Sponsor

Guerbet

1. Study Identification

Unique Protocol Identification Number

NCT03657784

Brief Title

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

Official Title

Pharmacokinetics, Dialysability and Safety of P03277, a New Gadolinium-based Contrast Agent, in Healthy Volunteers and in Patients With Impaired Renal Function

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

October 13, 2017 (Actual)

Primary Completion Date

February 1, 2019 (Actual)

Study Completion Date

August 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Guerbet

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Insufficiency, Healthy Volunteers

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Successive cohorts design and single dose administration

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 4

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 5

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

P03277

Other Intervention Name(s)

gadopiclenol

Intervention Description

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

Primary Outcome Measure Information:

Title

AUC

Description

AUC: area under the plasma concentration curve. Blood samples will be collected.

Time Frame

Prior to P03277 administration and at 2, 5, 10, 20, 30, 45 minutes and at 1, 2, 4, 6, 8, 12, 24 hours after administration for all cohorts. Additionally, after P03277 administration at 48 hours (cohorts 2-3-4), 72 hours (cohort 3) and 96 hours (cohort 4)

Title

Cmax

Description

Cmax: peak concentration. Blood samples will be collected.

Time Frame

Title

t1/2

Description

t1/2: terminal half-life. Blood samples will be collected.

Time Frame

Title

CLT

Description

CLT: total clearance. Blood samples will be collected.

Time Frame

Title

Description

Ae: amount excreted. Urine samples will be collected.

Time Frame

Prior to P03277 administration and during the intervals 0-6, 6-24, 24-48 hours for all cohorts + during 48-72 and 72-96 hours intervals for cohorts 2-3-4, 96-120 hours interval for cohorts 3-4, 120-144 hours and 144-168 hours intervals for cohort 4

Title

Relative amount of eliminated P03277 in blood

Description

This outcome will be assessed for cohort 5 only. Venous blood samples will be collected at each session of hemodialysis.

Time Frame

Just before the start of the session and at 30, 90 minutes and 4 hours after the start of the session.

Title

Clearance of P03277

Description

This outcome will be assessed for cohort 5 only and at the first hemodialysis only. Arterial and venous blood samples will be collected.

Time Frame

Just before the start of the session and at 30 and 90 minutes after the start of the session.

Title

Dialysis clearance of P03277

Description

This outcome will be assessed for cohort 5 only. Venous blood and dialysate samples will be collected at each session of hemodialysis.

Time Frame

Just before the start of the session and at 30, 90 minutes and 4 hours after the start of the session.

Secondary Outcome Measure Information:

Title

P03277concentration in blood (long-term)

Description

Blood samples will be collected.

Time Frame

At 1, 3 and 6 months after P03277 administration

Title

P03277 concentration in urine (long-term)

Description

Urine samples will be collected.

Time Frame

At 1, 3 and 6 months after P03277 administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Penescu Mircea, MD

Organizational Affiliation

Arensia Phase I unit "Carol Davila" Nephrology Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Republican Clinical Hospital, Arensia EM Unit

City

Chisinau

Country

Moldova, Republic of

Facility Name

Arensia Phase I unit "Carol Davila" Nephrology Hospital

City

Bucharest

Country

Romania

12. IPD Sharing Statement

Citations:

PubMed Identifier

34197356

Citation

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.

Results Reference

derived

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

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