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

NCT03657784 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: GDX-44-0052017-001211-36
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 2

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.

Conditions

Renal Insufficiency; Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• AUC

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

  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)

• Cmax

  Cmax: peak concentration. Blood samples will be collected.

  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)

• t1/2

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

  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)

• CLT

  CLT: total clearance. Blood samples will be collected.

  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)

• Ae

  Ae: amount excreted. Urine samples will be collected.

  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

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (2)

• P03277concentration in blood (long-term)

  At 1, 3 and 6 months after P03277 administration

• P03277 concentration in urine (long-term)

  At 1, 3 and 6 months after P03277 administration

Study Arms (5)

Cohort 1

EXPERIMENTAL

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

Drug: P03277

Cohort 2

EXPERIMENTAL

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

Drug: P03277

Cohort 3

EXPERIMENTAL

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

Drug: P03277

Cohort 4

EXPERIMENTAL

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

Drug: P03277

Cohort 5

EXPERIMENTAL

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

Drug: P03277

Interventions

P03277 DRUG

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

Also known as: gadopiclenol

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all subjects:
• Subject being 18 years or older, able and willing to participate in the trial
• For healthy volunteers / cohort 1:
• For patients with renal impairment / cohorts 2 to 5:
• Cohort 5: patient with end-stage renal failure who requires 3 hemodialysis sessions per week

Sponsors & Collaborators

• Guerbet: lead

Study Sites (2)

Republican Clinical Hospital, Arensia EM Unit

Chisinau, Moldova

Location

Arensia Phase I unit "Carol Davila" Nephrology Hospital

Bucharest, Romania

Location

Related Publications (1)

• 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.

  PMID: 34197356 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Interventions

gadopiclenol

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Penescu Mircea, MD

  Arensia Phase I unit "Carol Davila" Nephrology Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Successive cohorts design and single dose administration

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 5, 2018
• Study Start: October 13, 2017
• Primary Completion: February 1, 2019
• Study Completion: August 23, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-02

Locations

MO (1); RO (1)