A Study to Characterize the PK and PD Profile of IV FCM in Pediatric Subjects 1-17 Years Old With IDA
Study Details
Study Description
Brief Summary
This is a Phase II, open-label, non-randomized, multi-center, single arm study to characterize the pharmacokinetic and pharmacodynamics (PK/PD) profile of Ferric Carboxymaltose dosing in pediatric subjects with IDA after receiving either a 7.5 mg/kg or 15 mg/kg dose of Ferric Carboxymaltose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase II, open-label, non-randomized, multi-center, single arm study to characterize the pharmacokinetic and pharmacodynamics (PK/PD) profile of Ferric Carboxymaltose dosing in pediatric subjects with IDA after receiving either a 7.5 mg/kg or 15 mg/kg dose of Ferric Carboxymaltose.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ferric Carboxymaltose (FCM) FCM at 7.5 mg/kg or 15 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller |
Drug: Ferric Carboxymaltose (FCM)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Serum Concentration (Cmax) [prior to dosing and 1, 2, 6, 12, 48 and 72 hours post dosing]
Maximum observed serum concentration; obtained directly from the serum concentration-time profile.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female subjects 1 to 17 years of age with assent to participation and his/her parent or guardian is willing and able to sign the informed consent approved by the Independent Review Board / Ethics Committee.
-
Screening TSAT < 20%
-
Screening Hemoglobin < 11 g/dL
-
For subjects who are receiving an erythropoietin stimulating agent (ESA): stable ESA therapy (+/- 20% of current dose) for > 8 weeks prior to the qualifying screening visit and no ESA dosing or product changes anticipated for the length of the trial
Exclusion Criteria:
-
Known hypersensitivity reaction to any component of Ferric Carboxymaltose.
-
Subject previously randomized and treated in this study or any other clinical study of Ferric Carboxymaltose (FCM or VIT-45).
-
Body mass index (BMI) ≤ 5th percentile for age (see APPENDIX 2)
-
Male or Female subject 1 year of age weighing < 12kg.
-
History of acquired iron overload, hemochromatosis or other iron accumulation disorders.
-
Chronic kidney disease subjects on hemodialysis.
-
Screening Ferritin level > 300ng/mL
-
Subjects with significant severe diseases of the liver, hemopoietic system, cardiovascular system, psychiatric disorder or other conditions which on the opinion of the investigator may place a subject at added risk.
-
Any active infection.
-
Known positive hepatitis B antigen (HBsAg) or hepatitis C viral antibody (HCV) with evidence of active hepatitis.
-
Known positive HIV-1/HIV-2 antibodies (anti-HIV).
-
Anemia due to reasons other than iron deficiency (i.e. hemoglobinopathy). Subjects treated with vitamin B12 or folic acid deficiency are permitted.
-
Intravenous iron and /or blood transfusion in the 4 weeks prior to screening.
-
Immunosuppressive therapy that may lead to anemia (i.e. cyclophosphamide, azathioprine, mycophenolate mofetil). Note steroid therapy is permitted.
-
Administration and / or use of an investigational product (drug or device) within 30 days of screening.
-
Alcohol or drug abuse within the past six months.
-
Female subjects who are pregnant or lactating, or sexually active female who are of childbearing potential not willing to use an acceptable form of contraceptive precautions during the study.
-
Subject is unable to comply with study assessments.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Szpital Uniwersytecki Katedra i Klinika Pediatrii, Hematologii i Onkologii | Bydgoszcz | Poland | 85-094 | |
| 2 | Zespół Opieki Zdrowotnej w Dębicy z siedzibą w Dębicy , Oddział Dziecięcy | Dębica | Poland | 39-200 | |
| 3 | Uniwersytecki Szpital Dziecięcy w Krakowie, Oddział Pediatrii i Gastroenterologii (V) | Kraków | Poland | 30-663 | |
| 4 | Klinika Hematologii, Onkologii i Transplantologii Dziecięcej Uniwersytecki Szpital Dziecięcy w Lublinie | Lublin | Poland | 20-093 | |
| 5 | Oddział Ogólnopediatryczny; Uniwersytecki Szpital Dziecięcy w Lublinie | Lublin | Poland | 20-093 | |
| 6 | Indywidualna Specjalistyczna Praktyka lekarska z siedzibą w Rzeszowie | Rzeszów | Poland | 35-302 | |
| 7 | Klinika Pediatrii, Hematologii i Onkologii Dziecięcej | Szczecin | Poland | 71-252 | |
| 8 | Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii | Warszawa | Poland | 04-730 | |
| 9 | State Budgetary Educational Institution of Higher Professional Education "Ryazan State Medical University named after academician I.P. Pavlov" of the Ministry of Health of the Russian Federation | Ryazan' | Russian Federation | 390029 | |
| 10 | State Educational Institution of Higher Professional Education Saint Petersburg State Pediatric Medical Acamy of Ministry of Health and Social Development of the Russian Federation | Saint Petersburg | Russian Federation | 194100 |
Sponsors and Collaborators
- American Regent, Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 1VIT13036
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg/kg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg |
|---|---|---|
| Arm/Group Description | FCM at 7.5 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller Ferric Carboxymaltose (FCM) | FCM at 15mg/kg to a maximum single dose of 750mg iron, whichever is smaller |
| Period Title: Overall Study | ||
| STARTED | 16 | 19 |
| COMPLETED | 16 | 19 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Ferric Carboxymaltose (FCM) |
|---|---|
| Arm/Group Description | FCM at 7.5 mg/kg or 15 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller Ferric Carboxymaltose (FCM) |
| Overall Participants | 35 |
| Age (years) [Mean (Standard Deviation) ] | |
| Cohort 1 (FCM at 7.5 mg/kg to a maximum of 750mg) |
9.1
(6.13)
|
| Cohort 2 (FCM at 15 mg/kg to a maximum of 750mg) |
10.3
(5.77)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
28.6%
|
| Male |
6
17.1%
|
| Female |
9
25.7%
|
| Male |
10
28.6%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
35
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| Poland |
30
85.7%
|
| Russia |
5
14.3%
|
Outcome Measures
| Title | Maximum Serum Concentration (Cmax) |
|---|---|
| Description | Maximum observed serum concentration; obtained directly from the serum concentration-time profile. |
| Time Frame | prior to dosing and 1, 2, 6, 12, 48 and 72 hours post dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| In Cohort 1, pharmacokinetic parameter values are excluded for one subject due to anomalous and consistently high concentrations, and for one subject due to missing concentration data at 1 and 2 hours post-dose. |
| Arm/Group Title | Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg |
|---|---|---|
| Arm/Group Description | FCM at 7.5 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller Ferric Carboxymaltose (FCM) | FCM at 15 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller |
| Measure Participants | 14 | 19 |
| Mean (Standard Deviation) [µg/mL] |
157
(33.8)
|
310
(13.9)
|
Adverse Events
| Time Frame | Initial treatment with study drug through completion of day 35 (28 days post-dose for subjects who early terminated from the study). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg/kg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg | ||
| Arm/Group Description | FCM at 7.5 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller Ferric Carboxymaltose (FCM) | FCM at 15 mg/kg to a maximum single dose of 750 mg iron, whichever is smaller Ferric Carboxymaltose (FCM) | ||
All Cause Mortality |
||||
| Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg/kg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/19 (0%) | ||
Serious Adverse Events |
||||
| Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg/kg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/16 (12.5%) | 0/19 (0%) | ||
| Infections and infestations | ||||
| Sinusitis | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Upper Respiratory Tract Infection | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg/kg | Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/16 (56.3%) | 12/19 (63.2%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Eye disorders | ||||
| Blepharospasm | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Abdominal pain upper | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Aphthous stomatitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Constipation | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Enteritis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Gastroduodentitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Gastrooesophageal reflux disease | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Haematochezia | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| General disorders | ||||
| Hyperthermia | 0/16 (0%) | 0 | 2/19 (10.5%) | 2 |
| Infusion site pruritus | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Injection site pain | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Pyrexia | 2/16 (12.5%) | 2 | 0/19 (0%) | 0 |
| Thirst | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Infections and infestations | ||||
| Nasopharyngitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Pharyngitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Respiratory tract infection | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Sinusitis | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Upper respiratory tract infection | 1/16 (6.3%) | 1 | 2/19 (10.5%) | 2 |
| Urinary tract infection | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Viral pharyngitis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Aspartate aminotransferase increased | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Nervous system disorders | ||||
| Headache | 1/16 (6.3%) | 1 | 1/19 (5.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dysphonia | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Dyspnoea exertional | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Epistaxis | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Rhinorhoea | 0/16 (0%) | 0 | 3/19 (15.8%) | 3 |
| Wheezing | 1/16 (6.3%) | 1 | 1/19 (5.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
| Rash | 2/16 (12.5%) | 2 | 1/19 (5.3%) | 1 |
| Rash papular | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Urticaria | 0/16 (0%) | 0 | 3/19 (15.8%) | 3 |
| Vascular disorders | ||||
| Hot flush | 1/16 (6.3%) | 1 | 0/19 (0%) | 0 |
| Hypertension | 0/16 (0%) | 0 | 1/19 (5.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Angelia Butcher |
|---|---|
| Organization | Luitpold Pharmaceuticals, Inc. |
| Phone | 610-650-4200 ext 811 |
| abutcher@lpicrd.com |
- 1VIT13036