Safety and Acceptability of Deferiprone Delayed Release Tablets in Patients With Systemic Iron Overload (TWICE)

Safety, tolerability, and acceptability of twice-daily dosing with deferiprone delayed-release (DR) tablets in patients with systemic iron overload.

Study Overview

• Status: Completed
• Conditions: Iron Overload Due to Repeated Red Blood Cell Transfusions
• Intervention / Treatment: Drug: Deferiprone DR tablets 1000 mg (Low dosage); Drug: Deferiprone DR tablets 1000 mg (High dosage)

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St.Paul's Hospital
• Greece
  • Athens
    • Goudí, Athens, Greece, 11527
      • National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital
• Italy
  • Regione Gonzole
    • Orbassano (TO), Regione Gonzole, Italy, 10043
      • San Luigi Gonzaga University Hospital Reparto Microcitemie-Pediatria
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital/Weill Cornell Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Deferiprone DR tablets 1000 mg (Low dosage); Deferiprone DR tablets 1000 mg
Experimental: 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.	Drug: Deferiprone DR tablets 1000 mg (High dosage); Deferiprone DR tablets 1000 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 28
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.	Day 28

Collaborators and Investigators

• Sponsor: ApoPharma

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2019
• Primary Completion (Actual): December 4, 2019
• Study Completion (Actual): December 19, 2019

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: iron overload; chelation; Ferriprox; deferiprone
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Overload; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: LA61-0218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No