Chelation Therapy of Iron Overload With Pyridoxal Isonicotinoyl Hydrazone

NCT00000588 | Completed Phase 2 FDA Drug

• 2 other identifiers: 308R01HL042814
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

To demonstrate the safety and effectiveness of orally-administered pyridoxal isonicotinoyl hydrazone (PIH) for the chronic treatment of iron overload.

Conditions

Anemia (Iron-Loading); Beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies; Thalassemia; Iron Overload

Study Arms (2)

Chronic therapy of PIH according to medical condition

EXPERIMENTAL

Half of overall participants will get one of the following doses according to their medical condition: 1. Reducing the body iron burden to near-normal levels in non- transfusion-dependent patients with iron-loading anemias (requires chelate- induced iron excretion of at least 0.10 to 0.20 mg Fe/kg/day); 2. Maintaining near-normal body iron stores in transfusion-dependent patients who have previously been well-chelated with chronic subcutaneous or intravenous desferrioxamine (requires chelate-induced iron excretion of at least 0.25 to 0.40 mg Fe/kg/day); 3. Reducing the body iron burden to near-normal levels in iron-loaded, transfusion-dependent patients (requires chelate-induced iron excretion greater than 0.40 mg Fe/kg/day).

Drug: Chelation therapy; Other: Placebo

Placebo

PLACEBO COMPARATOR

Half of the participants will receive a Placebo: 1. Non-transfusion-dependent patients 2. Transfusion-dependent patients 3. Iron-loaded, transfusion-dependent patients

Drug: Chelation therapy; Other: Placebo

Interventions

Chelation therapy DRUG

After an initial 21 day balance study to demonstrate that a selected dose of PIH produced sufficient iron excretion, patients were begun on chronic therapy. PIH or placebo were given on days 4 to 9 and days 13 to 18 in a randomized, double-blind, cross-over design.

Also known as: Chronic therapy of Pyridoxal Isonicotinoyl Hydrazone

Chronic therapy of PIH according to medical condition; Placebo

Placebo OTHER

Placebo given at same time points as the Intervetnion for each clinical condition.

Also known as: Control

Chronic therapy of PIH according to medical condition; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting any of the following health conditions and eligible for Chronic PIH Treatment
• Non- transfusion-dependent patients with iron-loading anemias
• Transfusion-dependent patients who have previously been well-chelated with chronic subcutaneous or intravenous desferrioxamine
• Iron-loaded, transfusion-dependent patients
• Ages: 18-75 years old

You may not qualify if:

• Ages: 17 years old or younger or 76 years old or older

Sponsors & Collaborators

• Case Western Reserve University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Related Publications (4)

• Brittenham GM. Pyridoxal isonicotinoyl hydrazone. Effective iron chelation after oral administration. Ann N Y Acad Sci. 1990;612:315-26. doi: 10.1111/j.1749-6632.1990.tb24319.x. No abstract available.

  PMID: 2291560 BACKGROUND

• Brittenham GM. Pyridoxal isonicotinoyl hydrazone: an effective iron-chelator after oral administration. Semin Hematol. 1990 Apr;27(2):112-6. No abstract available.

  PMID: 2190317 BACKGROUND

• Nathan DG. An orally active iron chelator. N Engl J Med. 1995 Apr 6;332(14):953-4. doi: 10.1056/NEJM199504063321411. No abstract available.

  PMID: 7877655 BACKGROUND

• Olivieri NF, Brittenham GM, Matsui D, Berkovitch M, Blendis LM, Cameron RG, McClelland RA, Liu PP, Templeton DM, Koren G. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med. 1995 Apr 6;332(14):918-22. doi: 10.1056/NEJM199504063321404.

  PMID: 7877649 BACKGROUND

MeSH Terms

Conditions

Anemia; beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies; Thalassemia; Iron Overload

Interventions

Chelation Therapy

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Gary Brittenham

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Chronic dose according to condition: 1. Reducing the body iron burden to near-normal levels in non- transfusion-dependent patients with iron-loading anemias (requires chelate- induced iron excretion of at least 0.10 to 0.20 mg Fe/kg/day); 2. Maintaining near-normal body iron stores in transfusion-dependent patients who have previously been well-chelated with chronic subcutaneous or intravenous desferrioxamine (requires chelate-induced iron excretion of at least 0.25 to 0.40 mg Fe/kg/day); 3. Reducing the body iron burden to near-normal levels in iron-loaded, transfusion-dependent patients (requires chelate-induced iron excretion greater than 0.40 mg Fe/kg/day).

Study Record Dates

• First Submitted: October 27, 1999
• First Posted: October 28, 1999
• Study Start: June 5, 1989
• Primary Completion: March 31, 1993
• Study Completion: March 31, 1995
• Last Updated: September 21, 2022

Record last verified: 2022-09