Pharmacokinetics of Granule and Tablet Formulations of Deferitazole (Disodium Salt) and a Capsule Formulation of Deferitazole (Magnesium Hydroxide Salt)

A Phase 1, Open-label, Randomized, 3-Period, Relative Bioavailability Study Comparing the Pharmacokinetics of Granule and Tablet Formulations of Deferitazole (Disodium Salt) and a Capsule Formulation of Deferitazole (Magnesium Hydroxide Salt), Each Administered as a Single Oral Dose

The purpose of this study is to compare the pharmacokinetic profiles of deferitazole after administration of granule and tablet formulations of a deferitazole disodium salt to a capsule formulation of deferitazole magnesium hydroxide salt (reference formulation) in healthy adult subjects.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: Deferitazole (disodium salt, granule); Drug: Deferitazole (disodium salt, tablet); Drug: Deferitazole (magnesium hydroxide salt)

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-65 years inclusive at the time of consent.
2. Must be considered "healthy".
3. Serum ferritin, hemoglobin and erythrocyte indices (packed cell volume, mean corpuscular volume and mean corpuscular hemoglobin concentration) within normal range.

4. Willingness to comply with any applicable contraceptive requirements of the protocol and is:

   • Male, or
   • Female of non-childbearing potential (defined as a female who is post-menopausal )
   • Non-pregnant, non-lactating female
   • Females must be at least 90 days post partum or nulliparous.
5. Body weight equal to or greater than 60kg.
6. Ability to swallow a dose of the investigational product.

Exclusion Criteria:

1. Subject has a clinically significant history or a disorder detected during the medical interview/physical examination.
2. Acute illness.

3. Oral condition:

   • Has history of oral surgery (including extractions) within 4 weeks, operative dental work within 7 days, or a presence of any clinically significant oral pathology (as determined by the investigator) including lesions, sores or inflammation which would interfere with assessments.
   • Has fixed retainers, orthodontic appliances, or either maxillary and/or mandibular dentures or other appliances which may interfere with swilling or tasting the formulations.
   • Has current or recurrent disease that could affect the mouth and interfere with the taste assessment.
   • Has severe gingivitis, periodontitis or rampant caries.
   • Has the presence of oral or peri-oral ulceration including herpetic lesions
   • Has elective dentistry scheduled during the study duration.
4. Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment.
5. History of alcohol or other substance abuse within the year.
6. A positive screen for alcohol or drugs of abuse.
7. Confirmed systolic blood pressure >139mmHg or <89mmHg, and diastolic blood pressure >89mmHg or<49mmHg.
8. Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches.
9. Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day.
10. A positive human immunodeficiency virus antibody screen, hepatitis B surface antigen, or hepatitis C virus antibody.
11. Current use of any other medication (including over-the-counter, herbal, or homeopathic preparations)
12. Current use of iron supplements and/or multivitamins.
13. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products.
14. Donation of blood or blood products (e.g., plasma or platelets) within 60 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferitazole (disodium salt, granule)	Drug: Deferitazole (disodium salt, granule); Single oral dose of 1500 mg administered on Day 1; Other Names: SPD602, SSP-004184, SSP-004184SS
Experimental: Deferitazole (disodium salt, tablet)	Drug: Deferitazole (disodium salt, tablet); Single oral dose of 1500 mg administered on Day 1; Other Names: SPD602, SSP-004184, SSP-004184SS
Experimental: Deferitazole (magnesium hydroxide salt)	Drug: Deferitazole (magnesium hydroxide salt); Single oral dose of 2400 mg administered on Day 1; Other Names: SPD602, SSP-004184AQ, SSP-004184

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) of Deferitazole	AUC of disodium salt granule, disodium salt tablet, and magnesium hydroxide salt	Up to 120 hours post-dose
Maximum Plasma Concentration (Cmax) of Deferitazole	Cmax of disodium salt granule, disodium salt tablet, and magnesium hydroxide salt	Up to 120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Taste of Deferitazole		Immediately after dose and 5 minutes post-dose
Bioequivalence of Deferitazole Disodium Salt Granule Formulation With Tablet Formulation	Compare the pharmacokinetic profile of granule formulation with pharmacokinetic profile of tablet formulation	Up to 120 hours post-dose

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2014
• Primary Completion (Anticipated): March 19, 2014
• Study Completion (Anticipated): March 19, 2014

Study Registration Dates

• First Submitted: February 10, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 19, 2014

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Magnesium Hydroxide
• Other Study ID Numbers: SPD602-112