Renal ImpairmentPhase 4NCT01770652

An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild, Moderate, Severe, or No Renal Impairment

A Phase 4 study testing Deferiprone in people with Renal Impairment, run by ApoPharma at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Multi-center, non-randomized, open-label, single-dose, parallel group study to determine the effect of impaired renal function on the PK of deferiprone and its 3-O-glucuronide metabolite following a single oral dose of 33mg/kg Ferriprox®. Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: Deferiprone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 2 sitesCanada
Study dates: Jan 2013to Aug 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Main Inclusion Criteria:

All subjects:

Adult males or females, 18 - 75 years of age (inclusive);
Body weight ≥ 45 kg;
Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive);
Absolute neutrophil count (ANC) of >1.5x10^9/L;

Healthy volunteers:

Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
eGFR ≥ 90 mL/min/1.73m^2;

Renally impaired subjects:

Considered clinically stable in the opinion of the Investigator;
Subjects with mild renal impairment (eGFR 60-89 mL/min/1.73m^E2) OR moderate renal impairment (eGFR 30-59 mL/min/1.73m^2) OR severe renal impairment (eGFR 15-29 mL/min/1.73m^2).

Main Exclusion Criteria:

History of renal transplant;
Subjects undergoing any method of dialysis;
History or presence of clinically unstable significant respiratory, cardiovascular, pulmonary, hepatic, renal (except for subjects assigned to one of the renally impaired groups), hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease;
Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal product (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.);
Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females);
Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;
Participation in another clinical trial within 28 days prior to the study drug administration;

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T2M4
Algorithme Pharma Inc.
Mount Royal, Quebec, H3P3P1

Other trials in Canada

About this study

Official title: An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers

Read the detailed description

Post-marketing study to evaluate the effect of impaired renal function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild, moderate and severe renal impairment as compared to healthy volunteers.

Conditions: Renal Impairment
Being tested: Deferiprone
Keywords: Renal Impairment, Kidney Impairment, Kidney Disease, Ferriprox, Deferiprone, DFP (deferiprone), L1
Medical subject headings: Renal Insufficiency, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DeferiproneDrug
Also called Ferriprox, L1, DFP
Oral iron chelator

Study groups in NCT01770652
Study group	Role	What they receive
Normal renal function	Experimental	Healthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. Receives: Drug: Deferiprone
Mild Renal Impairment	Experimental	Mild impairment, defined as having an eGFR 60-89 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. Receives: Drug: Deferiprone
Moderate Renal Impairment	Experimental	Mild impairment, defined as having an eGFR 30-59 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. Receives: Drug: Deferiprone
Severe Renal Impairment	Experimental	Severe impairment, defined as having an eGFR 15-19 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. Receives: Drug: Deferiprone

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Measured: 24-hour interval
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).
Measured: 24 hour interval
AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-∞ was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Measured: 24 hour interval
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Measured: 24 hour interval
Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide
Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.
Measured: 24 hour interval
Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide
Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.
Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision.
Measured: 24-hour interval

Secondary outcomes (1)

Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.
The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of Ferriprox.
Measured: From time of dosing until 72 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2013Aug 2013

First posted18 Jan 2013 (estimated)
Study startJan 2013
Primary completionJul 2013
Study completionAug 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Renal ImpairmentStudies 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 4
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01770652
Sponsor's protocol ID: LA39-0412
Status last verified: Aug 2013
First submitted: 16 Jan 2013
Last updated: 26 Aug 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
Microbiota Changes Related to Outcomes in Kidney Transplantation
End-stage Renal Disease (ESRD), Kidney Transplantation
RecruitingObservational study
The KidneyCARE (Community Access to Research Equity) Study
Chronic Kidney Disease, Dialysis
Not yet recruiting
Effects of Minimally vs. Ultra-Processed Diets on Potassium (K) Handling in CKD
Chronic Kidney Disease
RecruitingPhase 1
Renal Impairment Pharmacokinetics (PK) Trial of Afabicin
Renal Impairment
RecruitingObservational study
Prevalence of Gastric Motor Dysfunction and Upper GI Symptoms in Gastric Antral Vascular Ectasias
Gastric Antral Vascular Ectasia, Cirrhosis

All Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers
ClinicalTrials.gov ID: NCT01770652
Acronym / sponsor ID: LA39-0412
Conditions: Renal Impairment
Keywords: Renal Impairment, Kidney Impairment, Kidney Disease, Ferriprox, Deferiprone, DFP (deferiprone), L1
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: ApoPharmaIndustry (pharma, biotech, devices)
Study start: Jan 2013
Primary completion: Jul 2013 (actual)
Study completion: Aug 2013 (actual)
First posted: 18 Jan 2013 (estimated)
Results: Posted 26 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Normal renal function	Experimental	Drug: DeferiproneHealthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Mild Renal Impairment	Experimental	Drug: DeferiproneMild impairment, defined as having an eGFR 60-89 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Moderate Renal Impairment	Experimental	Drug: DeferiproneMild impairment, defined as having an eGFR 30-59 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Severe Renal Impairment	Experimental	Drug: DeferiproneSevere impairment, defined as having an eGFR 15-19 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

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
DeferiproneAlso: Ferriprox, L1, DFPOral iron chelator	Drug	Mild Renal Impairment, Moderate Renal Impairment, Normal renal function, Severe Renal Impairment

Primary outcome

Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24-hour interval
Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24 hour interval
Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).
AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24 hour interval
AUC0-∞ was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24 hour interval
T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.
Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24 hour interval
Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.
Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24-hour interval
Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose. Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision.

1 secondary outcome

Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.
Time frame: From time of dosing until 72 hours post-dose

Results and safety

Results posted to the registry on 26 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Hepatic Function (Healthy Volunteers)	8	8
Mild Renal Impairment	8	8
Moderate Renal Impairment	8	8
Severe Renal Impairment	8	8

Primary outcome: Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide

Time frame: 24-hour interval. Mean (Standard Deviation). Unit: μg/mL

Measure	Normal Renal Function (Healthy Volunteers) n = 8	Mild Renal Impairment n = 8	Moderate Renal Impairment n = 8	Severe Renal Impairment n = 8
Cmax for serum deferiprone	37.1 (12.0)	33.4 (9.5)	43.3 (22.9)	30.6 (16.2)
Cmax for serum deferiprone-3-o-glucuronide	47.8 (6.2)	60.8 (10.3)	118.8 (48.3)	150.8 (32.4)

Population analysed: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Primary outcome: Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide

Time frame: 24 hour interval. Median (Full Range). Unit: hour

Measure	Normal Renal Function n = 8	Mild Renal Impairment n = 8	Moderate Renal Impairment n = 8	Severe Renal Impairment n = 8
Tmax for Serum Deferiprone	0.50 (0.25 to 1.00)	0.75 (0.50 to 1.00)	1.00 (0.50 to 2.00)	0.75 (0.25 to 4.00)
Tmax for Serum Deferiprone 3-O-glucuronide	2.50 (1.33 to 3.00)	2.50 (2.00 to 3.00)	3.00 (2.00 to 6.00)	4.00 (2.00 to 6.00)

Population analysed: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Primary outcome: AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide

Time frame: 24 hour interval. Mean (Standard Deviation). Unit: μg*h/mL

Measure	Normal Renal Function n = 8	Mild Renal Impairment n = 8	Moderate Renal Impairment n = 8	Severe Renal Impairment n = 8
AUC0-∞ for serum deferiprone 3-O-Glucuronide	78.1 (27.8)	76.9 (15.7)	74.9 (15.1)	70.9 (8.5)
AUC0-∞ for serum deferiprone	252.6 (35.4)	319.1 (54.1)	703.2 (229.6)	1438.5 (335.5)

Population analysed: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Primary outcome: T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide

Time frame: 24 hour interval. Mean (Standard Deviation). Unit: hour

Measure	Normal Renal Function n = 8	Mild Renal Impairment n = 8	Moderate Renal Impairment n = 8	Severe Renal Impairment n = 8
T1/2 for Serum Deferiprone	1.68 (0.27)	1.77 (0.17)	2.03 (0.32)	2.20 (0.91)
T1/2 for Serum Deferiprone 3-O-Glucuronide	2.14 (0.32)	2.58 (0.45)	2.58 (0.38)	3.35 (0.48)

Population analysed: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 4 days: from the time of administration of study drug until a follow-up telephone call 48 to 72 hours after discharge. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Hepatic Function (Healthy Volunteers)	0 of 8 (0%)	2 of 8 (25%)	Not reported
Mild Renal Impairment	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Moderate Renal Impairment	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
Severe Renal Impairment	0 of 8 (0%)	1 of 8 (12.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Renal Impairment

Not yet recruitingObservational study
Microbiota Changes Related to Outcomes in Kidney Transplantation
End-stage Renal Disease (ESRD), Kidney Transplantation
RecruitingObservational study
The KidneyCARE (Community Access to Research Equity) Study
Chronic Kidney Disease, Dialysis
Not yet recruiting
Effects of Minimally vs. Ultra-Processed Diets on Potassium (K) Handling in CKD
Chronic Kidney Disease
RecruitingPhase 1
Renal Impairment Pharmacokinetics (PK) Trial of Afabicin
Renal Impairment
RecruitingObservational study
Prevalence of Gastric Motor Dysfunction and Upper GI Symptoms in Gastric Antral Vascular Ectasias
Gastric Antral Vascular Ectasia, Cirrhosis

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.

Fernando Tricta, MD study chair

ApoPharma

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Deferiprone in people with Renal Impairment, run by ApoPharma at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 26 Aug 2014. 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 Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide (time frame: 24-hour interval). The study lists 6 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 NCT01770652.

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 26 Aug 2014.