Iron Overload Due to Repeated Red Blood Cell Transfusions
Conditions
Keywords
iron overload, chelation, deferiprone, Ferriprox
Brief summary
Safety, tolerability, and acceptability of twice-daily dosing with deferiprone delayed-release (DR) tablets in patients with systemic iron overload.
Detailed description
This study is looking at the safety, tolerability, and acceptability of twice-daily dosing with deferiprone delayed-release (DR) tablets in patients with systemic iron overload who are currently taking deferiprone immediate-release tablets (Ferriprox) three times a day. Ferriprox doses range from 75 milligrams per kilogram of body weight (mg/kg) per day to 100 mg/kg per day. Half the patients in the study will be on a dosage that is closer to the low end of the range, and half will be on a dosage that is closer to the high end. Both groups will be switched for one month to deferiprone DR tablets at approximately the same total daily dosage that they have been taking for Ferriprox.
Interventions
DRUGDeferiprone DR tablets 1000 mg (Low dosage)
Deferiprone DR tablets 1000 mg
DRUGDeferiprone DR tablets 1000 mg (High dosage)
Deferiprone DR tablets 1000 mg
Sponsors
ApoPharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥ 18 years. 2. Diagnosis of thalassemia syndrome, sickle cell disease, or other disorder requiring a regular regimen of red blood cell transfusions. 3. On a stable regimen (≥3 months) of Ferriprox tablets for the treatment of systemic iron overload. 4. Absolute neutrophil count ≥1.5 x 10\^9/L at screening. 5. A record of at least 12 measured alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.
Exclusion criteria
1. Receipt of any iron chelator other than Ferriprox (i.e., combination therapy) in the last 3 months, or planning to receive it at any time during the period of the study. 2. ALT and/or AST value \> 5 times the upper limit of normal (ULN) at screening 3. Active case of hepatitis B or C at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern. | Day 28 | Levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) will be assessed throughout the study to determine if any patients have post-dose increases that are considered to be a safety concern. The criteria for being considered a safety concern are meeting one of the following: * For a patient whose level was within the normal range at baseline, the criterion is reaching a value of 5 times the upper limit of normal (ULN) * For a patient whose level was above the ULN at baseline, the criterion is reaching either 5 times the baseline value or 10 x ULN |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress. | Day 28 | Patients will be asked to report any events of GI distress during the study, such as nausea, vomiting, diarrhea, abdominal pain, and dyspepsia. |
| The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation. | Day 28 | At the end of the study, patients will complete a questionnaire to indicate which formulation they prefer. |
Countries
Canada, Greece, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dosage Patients in this group will receive a total daily dosage of deferiprone DR tablets that is closer to 75 mg/kg/day. The total dosage will be divided into two equal parts, taken about 12 hours apart.
Deferiprone DR tablets 1000 mg (Low dosage): Deferiprone DR tablets 1000 mg | 15 |
| High Dosage Patients in this group will receive a total daily dosage of deferiprone DR tablets that is closer to 100 mg/kg/day. The total dosage will be divided into two equal parts, taken about 12 hours apart.
Deferiprone DR tablets 1000 mg (High dosage): Deferiprone DR tablets 1000 mg | 14 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | High Dosage | Low Dosage | Total |
|---|---|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 6.8 | 41.9 years STANDARD_DEVIATION 9.9 | 41.1 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 15 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Level of liver enzymes at baseline for high-dosage group Baseline ALT | 38.29 units per liter STANDARD_DEVIATION 22.43 | — | 38.29 units per liter STANDARD_DEVIATION 22.43 |
| Level of liver enzymes at baseline for high-dosage group Baseline AST | 28.50 units per liter STANDARD_DEVIATION 11.39 | — | 28.50 units per liter STANDARD_DEVIATION 11.39 |
| Level of liver enzymes at baseline for low-dosage group Baseline ALT | — | 29.60 units per liter STANDARD_DEVIATION 19.88 | 29.60 units per liter STANDARD_DEVIATION 19.88 |
| Level of liver enzymes at baseline for low-dosage group Baseline AST | — | 27.53 units per liter STANDARD_DEVIATION 10 | 27.53 units per liter STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 26 Participants |
| Region of Enrollment Canada | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Greece | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Italy | 7 participants | 8 participants | 16 participants |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 10 / 15 | 9 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 |
Outcome results
Primary
The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern.
Levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) will be assessed throughout the study to determine if any patients have post-dose increases that are considered to be a safety concern. The criteria for being considered a safety concern are meeting one of the following: * For a patient whose level was within the normal range at baseline, the criterion is reaching a value of 5 times the upper limit of normal (ULN) * For a patient whose level was above the ULN at baseline, the criterion is reaching either 5 times the baseline value or 10 x ULN
Time frame: Day 28
Population: One patient in the high-dosage group withdrew before providing any evaluable data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dosage | The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern. | Patients with elevated ALT of clinical concern | 0 Participants |
| Low Dosage | The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern. | Patients with elevated AST of clinical concern | 0 Participants |
| High Dosage | The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern. | Patients with elevated ALT of clinical concern | 0 Participants |
| High Dosage | The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern. | Patients with elevated AST of clinical concern | 0 Participants |
Secondary
The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation.
At the end of the study, patients will complete a questionnaire to indicate which formulation they prefer.
Time frame: Day 28
Population: One of the evaluable patients withdrew before completing the questionnaire
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dosage | The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation. | 13 Participants |
| High Dosage | The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation. | 13 Participants |
Comparison: One-sample proportion test to determine if the overall preference for deferiprone DR was greater than chance (i.e., a 50% preference for each formulation)p-value: 0.0074One-sample proportion test
Comparison: One-sample proportion test to determine if the overall preference for deferiprone DR was greater than chance (i.e., a 50% preference for each formulation)p-value: 0.0002One-sample proportion test
Secondary
The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress.
Patients will be asked to report any events of GI distress during the study, such as nausea, vomiting, diarrhea, abdominal pain, and dyspepsia.
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dosage | The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress. | 3 Participants |
| High Dosage | The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress. | 3 Participants |