Safety and Pharmacokinetic Study of Escalating Multiple Doses of an Iron Chelator in Patients With Iron Overload

Sponsor

FerroKin BioSciences, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01039636

Collaborator

(none)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this research study is to study the safety of increasing doses of FBS0701, and to see how quickly the study medication is absorbed and how quickly it disappears from the bloodstream. FBS0701 is a new, oral iron chelator - a medication taken by mouth that increases the body's elimination of iron. Iron chelators are used in patients who develop iron overload from their transfusions. Four increasing doses of FBS0701 will be tested during this study. The study will start with the lowest dose given to 4 patients (3 mg/kg/day. The next group of 4 patients will receive the next high dose (8mg/kg/day only after the results of the first 4 patients are examined and it is determined safe to continue. Participating patients will take the study medication for 7 days and be followed for 28 days after their last dose to determine if they have any reactions to the study medication - therefore a total of 35 days on study. Patients will need to give up to 17 blood samples over the screening period and first 15 days of the study (a total of about 9 tablespoons). Patients will not need to stay overnight in the clinic but will need to visit the clinic 10 times for screening and on-study visits over the 35 days. Patients currently taking an iron chelator will need to stop that treatment for up to 22 days (up to 5 days before they start the study and for 15 days during the study). The results of this study will be helpful in determining the safety of the drug and the best doses of FBS0701 to be used in the next study which will assess the effectiveness of this new iron chelator.

Condition or Disease	Intervention/Treatment	Phase
Transfusional Iron Overload Beta-thalassemia	Drug: FBS0701	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE 1b OPEN LABEL, MULTI-CENTER, ESCALATING MULTIPLE DOSE STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF FBS0701 IN PATIENTS WITH TRANSFUSIONAL IRON OVERLOAD

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FBS0701 - 5 escalating doses 5 escalating doses of FBS0701 in 5 cohorts of 4 patients each.	Drug: FBS0701 Oral FBS0701 for 7 days at one of the following doses: 3 mg/kg/day or 8 mg/kg/day or 16 mg/kg/day or 32 mg/kg/day or 40 mg/kg/day

Arm

Intervention/Treatment

Experimental: FBS0701 - 5 escalating doses

5 escalating doses of FBS0701 in 5 cohorts of 4 patients each.

Drug: FBS0701

Oral FBS0701 for 7 days at one of the following doses: 3 mg/kg/day or 8 mg/kg/day or 16 mg/kg/day or 32 mg/kg/day or 40 mg/kg/day

Outcome Measures

Primary Outcome Measures

Safety and tolerability by AEs, Physical Exam, Clinical Laboratory assessments [35 days (7 days treatment and 28 days follow up)]
Steady state plasma level and half-life of FBS0701 [7 days of dosing]

Secondary Outcome Measures

Urinary excretion of iron [7 days of dosing]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

At least 18 years old
Transfusion dependent (at least 8 transfusions per year) with transfusional iron overload needing treatment with deperoxamine, deferasirox or deperiprone.
Willing to discontinue current iron chelation therapy for 2-5 days prior to enrollment and for a total of up to 3 weeks
Willing to fast after midnight prior to each dose
Serum ferritin greater than 400ng/ml
Liver iron concentration greater than or equal to 1.5 mg iron. (determined by MRI or SQUID within 12 months prior to enrollment)
Cardiac iron greater than or equal to 12 milliseconds (determined by MRI t2* within 18 months prior to enrollment)
Mean of last 3 pre-transfusion hemoglobin values must be greater than or equal to 7.5 g/dl
Agrees to use approved contraception from Screening and until 30 days after last administration of study drug. Abstinence OK.

Exclusion Criteria:

Principal Investigator considers patient unfit for study after conducting a medical review, physical examination and other screening assessments.
Non-elective hospitalization with past 30 days
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric or skin disorder.
Evidence of significant renal insufficiency; serum creatine above upper limit of normal or proteinuria greater than 2 gm per day or calculated creatinine clearance of less than or equal to 60ml/min
Platelet count below 150,000,000/ml and/or absolute neutrophil count less then 1500/mm3
Alkaline phosphatase or AST greater than 5 times the upper limit of normal or ALT greater than 4 times the upper limit of normal
Female patients who are pregnant or lactating
Use of any investigational agent within the last 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Oakland	Oakland	California	United States	94609
2	Children's Hospital of Boston	Boston	Massachusetts	United States	02115
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
4	Royal Adelaide Hospital	Adelaide		Australia
5	Siriraj Hospital, Mahidol University	Bangkok		Thailand	10700