Hepatic ImpairmentPhase 4NCT01767103

An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild and Moderate Hepatic Insufficiency and Healthy Volunteers

A Phase 4 study testing Ferriprox® in people with Hepatic Impairment, run by ApoPharma at 2 sites in United States.

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 hepatic 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: Hepatic Impairment
What is being tested?: Ferriprox®
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 2 sitesUnited States
Study dates: Jan 2013to Apr 2014
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 ≥ 50 kg;
Body mass index (BMI) between 19 and 32 kg/mE2 (inclusive);
Absolute neutrophil count (ANC) of >1.5x10E9/L ;

Healthy volunteers:

Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
Matched to hepatically impaired subjects in the study by age (+/- 10 years), sex and weight (+/- 15% BMI).

Hepatically impaired subjects:

Considered clinically stable in the opinion of the Investigator;
Subjects with different degrees of impaired hepatic function as assessed by a Child-Pugh classification score: mild (Class A: 5-6 points) and moderate (Class B: 7-9 points) impaired hepatic function.

Main Exclusion Criteria:

For subjects with hepatic impairment, fluctuating or rapidly deteriorating hepatic function as indicated by clinical and/or laboratory signs of hepatic impairment (e.g. advanced ascites, infection of ascites, fever, or active gastrointestinal bleeding).
Evidence of liver impairment in healthy volunteers: hepatitis B and C; or aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, clotting factors, serum protein that is considered clinically significant by the Investigator;
History or presence of significant clinically unstable respiratory, cardiovascular, pulmonary, hepatic (except for subjects assigned to one of the hepatically impaired groups), renal, hematologic, gastrointestinal, endocrine (except for subjects with hepatic impairment with clinically stable and treated diabetes, hypertension and thyroid disorders), 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. resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, clinically unstable endocrine disease, severe infections, acute inflammations, etc.);
Received a pharmacological agent in another clinical trial within 28 days prior to the first dose of the study;

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Miami
Miami, Florida, 33136
Orlando Clinical Research Center
Orlando, Florida, 32809

Other trials in United States

About this study

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

Read the detailed description

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

Conditions: Hepatic Impairment
Being tested: Ferriprox®
Keywords: Hepatic Impairment, Liver Impairment, Liver Disease, Ferriprox®, LI, DFP, Deferiprone
Medical subject headings: Liver Diseases

What participants receive

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

Ferriprox®Drug
Also called DFP, Deferiprone, L1

Study groups in NCT01767103
Study group	Role	What they receive
Normal Hepatic Function (healthy volunteers)	Experimental	Healthy volunteers with normal hepatic function received a single 33 mg/kg dose of Ferriprox®. Receives: Drug: Ferriprox®
Mild Hepatic Failure	Experimental	Subjects with mild hepatic failure as defined by the Child-Pugh Class C: 5-6 points received a single 33 mg/kg dose of Ferriprox®. Receives: Drug: Ferriprox®
Moderate Hepatic Failure	Experimental	Subjects with moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points received a single 33 mg/kg dose of Ferriprox®. Receives: Drug: Ferriprox®

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 hepatic function, mild hepatic impairment, or moderate hepatic 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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC (area under the curve) from zero to infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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
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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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
CumAe for Urine Deferiprone and Deferiprone 3-O-glucuronide
Cumulative amount of deferiprone and deferiprone 3-O-glucuronide excreted in the urine. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose.
Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).
Measured: 24-hour interval
Fe% for Urine Deferiprone and Deferiprone 3-O-glucuronide
Cumulative fraction of Ferriprox dose excreted in urine as deferiprone or deferiprone 3-O-glucuronide. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose.
Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).
Measured: 24-hour interval

Secondary outcomes (1)

Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment.
The number of participants who experienced adverse events following a single dose of Ferriprox, between the time of dosing and the follow-up visit (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests).
Measured: Time of dosing until 48 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 2013Apr 2014

First posted14 Jan 2013 (estimated)
Study startJan 2013
Primary completionApr 2014
Study completionApr 2014

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 Hepatic 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: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01767103
Sponsor's protocol ID: LA40-0412
Status last verified: Apr 2014
First submitted: 9 Jan 2013
Last updated: 10 Sep 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

RecruitingPhase 1
A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Normal Hepatic Function and Participants With Hepatic Impairment
Hepatic Impairment
RecruitingPhase 1
A Phase I Study to Investigate the Effect of Hepatic Impairment of AZD9550 and AZD6234
Hepatic Impairment
Not yet recruitingPhase 1
Aleniglipron Hepatic Impairment Study
Hepatic Impairment
Not yet recruitingPhase 1
A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sonrotoclax in Participants With Severe Hepatic Impairment
Hepatic Impairment, Healthy Adult Participants
Not yet recruitingPhase 1
A Study to Assess the Safety, Tolerability and Pharmacokinetics of ABI-6250 in Participants With Mild Hepatic Impairment Compared With Participants With Normal Hepatic Function
Mild Hepatic Imparement

All Hepatic Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 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 Hepatic Function and Healthy Volunteers
ClinicalTrials.gov ID: NCT01767103
Acronym / sponsor ID: LA40-0412
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment, Liver Impairment, Liver Disease, Ferriprox®, LI, DFP, Deferiprone
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: ApoPharmaIndustry (pharma, biotech, devices)
Study start: Jan 2013
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 14 Jan 2013 (estimated)
Results: Posted 10 Sep 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: 3

Arm	Type	Receives
Normal Hepatic Function (healthy volunteers)	Experimental	Drug: Ferriprox®Healthy volunteers with normal hepatic function received a single 33 mg/kg dose of Ferriprox®.
Mild Hepatic Failure	Experimental	Drug: Ferriprox®Subjects with mild hepatic failure as defined by the Child-Pugh Class C: 5-6 points received a single 33 mg/kg dose of Ferriprox®.
Moderate Hepatic Failure	Experimental	Drug: Ferriprox®Subjects with moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points received a single 33 mg/kg dose of Ferriprox®.

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
Ferriprox®Also: DFP, Deferiprone, L1	Drug	Mild Hepatic Failure, Moderate Hepatic Failure, Normal Hepatic Function (healthy volunteers)

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 hepatic function, mild hepatic impairment, or moderate hepatic 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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24-hour interval
AUC (area under the curve) from zero to infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
CumAe for Urine Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24-hour interval
Cumulative amount of deferiprone and deferiprone 3-O-glucuronide excreted in the urine. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose. Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).
Fe% for Urine Deferiprone and Deferiprone 3-O-glucuronide
Time frame: 24-hour interval
Cumulative fraction of Ferriprox dose excreted in urine as deferiprone or deferiprone 3-O-glucuronide. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose. Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).

1 secondary outcome

Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment.
Time frame: Time of dosing until 48 hours post-dose

Results and safety

Results posted to the registry on 10 Sep 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)	7	7
Mild Hepatic Failure	7	7
Moderate Hepatic Failure	7	7

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

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

Measure	Normal Hepatic Function (Healthy Volunteers) n = 7	Mild Hepatic Failure n = 7	Moderate Hepatic Failure n = 7
Cmax for serum deferiprone	49.00 (24.081)	36.26 (8.4799)	35.94 (7.8407)
Cmax for serum deferiprone 3-O-glucuronide	69.03 (9.9153)	56.91 (11.416)	55.33 (25.335)

Population analysed: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter

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

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

Measure	Normal Hepatic Function (Healthy Volunteers) n = 7	Mild Hepatic Failure n = 7	Moderate Hepatic Failure n = 7
Tmax of deferiprone	0.7500 (0.500 to 2.00)	0.7500 (0.500 to 1.00)	0.7500 (0.500 to 1.33)
Tmax of deferiprone 3-O-glucuronide	2.000 (1.00 to 3.00)	3.000 (1.67 to 4.00)	3.000 (3.00 to 4.00)

Population analysed: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter

Primary outcome: AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide

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

Measure	Normal Hepatic Function (Healthy Volunteers) n = 7	Mild Hepatic Failure n = 7	Moderate Hepatic Failure n = 7
AUC0-∞ for serum deferiprone	92.64 (19.221)	82.02 (28.213)	105.5 (41.684)
AUC0-∞ for serum deferiprone 3-O-glucuronide	337.3 (45.343)	305.1 (53.651)	305.9 (111.75)

Population analysed: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK 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 Hepatic Function (Healthy Volunteers) n = 7	Mild Hepatic Failure n = 7	Moderate Hepatic Failure n = 7
T1/2 for serum deferiprone	1.994 (0.26971)	1.855 (0.45370)	2.180 (0.83153)
T1/2 for deferiprone 3-O-glu	2.621 (0.35653)	2.518 (0.55679)	2.479 (0.67212)

Population analysed: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 2 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Hepatic Function (Healthy Volunteers)	0 of 7 (0%)	0 of 7 (0%)	Not reported
Mild Hepatic Failure	0 of 7 (0%)	1 of 7 (14.3%)	Not reported
Moderate Hepatic Failure	1 of 7 (14.3%)	3 of 7 (42.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Hepatic Impairment

RecruitingPhase 1
A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Normal Hepatic Function and Participants With Hepatic Impairment
Hepatic Impairment
RecruitingPhase 1
A Phase I Study to Investigate the Effect of Hepatic Impairment of AZD9550 and AZD6234
Hepatic Impairment
Not yet recruitingPhase 1
Aleniglipron Hepatic Impairment Study
Hepatic Impairment
Not yet recruitingPhase 1
A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sonrotoclax in Participants With Severe Hepatic Impairment
Hepatic Impairment, Healthy Adult Participants
Not yet recruitingPhase 1
A Study to Assess the Safety, Tolerability and Pharmacokinetics of ABI-6250 in Participants With Mild Hepatic Impairment Compared With Participants With Normal Hepatic Function
Mild Hepatic Imparement

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 Ferriprox® in people with Hepatic Impairment, run by ApoPharma at 2 sites in United States.

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 10 Sep 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 United States. 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 10 Sep 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 NCT01767103.

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 10 Sep 2014.