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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03657784
• Other study ID #: GDX-44-005
• Secondary ID: 2017-001211-36
• Status: Completed
• Phase: Phase 1
• Start date: October 13, 2017
• Est. completion date: August 23, 2019

Study information

• Verified date: February 2019
• Source: Guerbet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 23, 2019
• Est. primary completion date: February 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Renal Insufficiency

Intervention

Drug:
• P03277
Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second

Locations

Country	Name	City	State
Moldova, Republic of	Republican Clinical Hospital, Arensia EM Unit	Chisinau
Romania	Arensia Phase I unit "Carol Davila" Nephrology Hospital	Bucharest

Sponsors (1)

Lead Sponsor	Collaborator
Guerbet

Countries where clinical trial is conducted

Moldova, Republic of,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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.
Primary	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.
Primary	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	P03277concentration in blood (long-term)	Blood samples will be collected.	At 1, 3 and 6 months after P03277 administration
Secondary	P03277 concentration in urine (long-term)	Urine samples will be collected.	At 1, 3 and 6 months after P03277 administration