Renal InsufficiencyPhase 1NCT03657784
Pharmacokinetics, Dialysability and Safety of P03277 in Healthy Volunteers and in Patients With Impaired Renal Function
A Phase 1 study testing P03277 in people with Renal Insufficiency and Healthy Volunteers, run by Guerbet at 2 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Insufficiency, Healthy Volunteers
- What is being tested?
- P03277
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 13 Oct 2017to 23 Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 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:
Show all 10Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Romania1 site
Arensia Phase I unit "Carol Davila" Nephrology Hospital
Bucharest
About this study
Official title: Pharmacokinetics, Dialysability and Safety of P03277, a New Gadolinium-based Contrast Agent, in Healthy Volunteers and in Patients With Impaired Renal Function
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.
Read the 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
- Being tested
- P03277
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P03277Drug
Also called gadopiclenol
Single intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: P03277 |
| Cohort 5 | Experimental | P03277 will be administered to patients with end-stage renal failure who requires 3 hemodialysis sessions per week. Receives: Drug: P03277 |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
AUC: area under the plasma concentration curve. Blood samples will be collected.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Blood samples will be collected.
Measured: At 1, 3 and 6 months after P03277 administration
P03277 concentration in urine (long-term)
Urine samples will be collected.
Measured: At 1, 3 and 6 months after P03277 administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start13 Oct 2017
- Primary completion1 Feb 2019
- Study completion23 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal InsufficiencyStudies 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
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Successive cohorts design and single dose administration
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guerbet
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Penescu Mircea, MD, Principal investigator, Arensia Phase I unit "Carol Davila" Nephrology Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03657784
- Sponsor's protocol ID
- GDX-44-005
- Other IDs
- 2017-001211-36, 2017
- Status last verified
- Feb 2019
- First submitted
- 31 Aug 2018
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34197356
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics, Dialysability and Safety of P03277, a New Gadolinium-based Contrast Agent, in Healthy Volunteers and in Patients With Impaired Renal Function
- ClinicalTrials.gov ID
- NCT03657784
- Acronym / sponsor ID
- GDX-44-005
- Conditions
- Renal Insufficiency, Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- GuerbetIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2017 (actual)
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 23 Aug 2019 (actual)
- First posted
- 5 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Successive cohorts design and single dose administration
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: P03277P03277 will be administered to healthy volunteers with stable normal renal function defined with an absolute value of eGFR ≥ 90 mL/min. |
| Cohort 2 | Experimental | Drug: P03277P03277 will be administered to patients with stable mild renal impairment defined with an absolute value of eGFR between 60 and 89 mL/min. |
| Cohort 3 | Experimental | Drug: P03277P03277 will be administered to patients with stable moderate renal impairment defined with an absolute value of eGFR between 30 and 59 mL/min. |
| Cohort 4 | Experimental | Drug: P03277P03277 will be administered to patients with stable severe renal impairment defined with an absolute value of eGFR between 15 and 29 mL/min. |
| Cohort 5 | Experimental | Drug: P03277P03277 will be administered to patients with end-stage renal failure who requires 3 hemodialysis sessions per week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- 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
- 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
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: gadopiclenolSingle intravenous bolus injection at 0.1 mmol/kg body weight at a rate of 2 mL/second | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
AUC
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)
AUC: area under the plasma concentration curve. Blood samples will be collected.
Cmax
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)
Cmax: peak concentration. Blood samples will be collected.
t1/2
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)
t1/2: terminal half-life. Blood samples will be collected.
CLT
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)
CLT: total clearance. Blood samples will be collected.
Ae
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
Ae: amount excreted. Urine samples will be collected.
Relative amount of eliminated P03277 in blood
Time frame: Just before the start of the session and at 30, 90 minutes and 4 hours after the start of the session.
This outcome will be assessed for cohort 5 only. Venous blood samples will be collected at each session of hemodialysis.
Clearance of P03277
Time frame: Just before the start of the session and at 30 and 90 minutes after the start of the session.
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
Time frame: Just before the start of the session and at 30, 90 minutes and 4 hours after the start of the session.
This outcome will be assessed for cohort 5 only. Venous blood and dialysate samples will be collected at each session of hemodialysis.
2 secondary outcomes
P03277concentration in blood (long-term)
Time frame: At 1, 3 and 6 months after P03277 administration
P03277 concentration in urine (long-term)
Time frame: At 1, 3 and 6 months after P03277 administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Derived from this study: PubMed 34197356Bradu 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.
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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.
Penescu Mircea, MD principal investigator
Arensia Phase I unit "Carol Davila" Nephrology Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing P03277 in people with Renal Insufficiency and Healthy Volunteers, run by Guerbet at 2 sites in 2 countries.
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 10 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 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Moldova, Romania. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
AUC (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)). The study lists 8 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 NCT03657784, 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 22 Oct 2019.