Effects of Iron Supplements on the Pharmacokinetics of MT-6548

A Clinical Pharmacological Study to Evaluate the Effects of Iron Supplements on the Pharmacokinetics of MT-6548 in Healthy Male Volunteers

The objectives of this study are to investigate the pharmacokinetics and safety of MT-6548 co-administered with iron supplements in healthy male volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MT-6548; Drug: Iron supplement A; Drug: Iron supplement B; Drug: Iron supplement C; Drug: Iron supplement D

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Parents and each grandparent of subjects are Japanese
• Subjects judged as appropriate for this study by investigators based on the results of the tests at Screening, Day -1 and Day 1

Exclusion Criteria:

• Subjects with signs of heart diseases on the result of screening test
• Subjects with current conditions or histories of drug addiction or alcohol addiction
• Subjects judged by investigators that they cannot comply with the prohibition during the confinement period
• Subjects who have taken MT-6548 before
• Subjects with current conditions or histories of drug or food allergies
• Subjects with BMI below18.5 kg/m2, BMI above 25.0 kg/m2 or body weight below 50.0 kg at the screening test
• Subjects who have undergone platelet or plasma donation 2 weeks prior to the consent
• Subjects who have undergone blood donation or blood draw of 400 mL or above within 12 weeks prior to the consent, or 200 mL or above within 4 weeks prior to the consent
• Subjects who have undergone blood donation or blood draw of 800 mL or above within one year prior to the consent
• Subjects who have undergone surgical operations that can affect gastrointestinal absorption of medication (appendectomy and hernioplasty do not meet this exclusion criterion)
• Subjects with positive results for HBs antigen, syphilis serum reaction, HCV antibody or HIV antigen / antibody at the screening test
• Subjects who are unwilling to consent to use contraception from the beginning of study period to 90 days following the final dose of the study drug
• Subjects who have participated in another clinical study and received study drugs within 12 weeks prior to consent, or within 5 times the half-life of the study drug (whichever is longer)
• Subjects who have taken any medications except for the drug used for this clinical study within 7 days prior to the first dose of the study drug
• Subjects who have had supplements within 7 days prior to the first dose of the study drug
• Subjects who have had apples, citrus fruits such as grapefruits or any food products that contain apples or citrus fruits within 7 days prior to the first dose of the study drug
• Subjects who have had food products which contain St John's Wort within 2 weeks prior to the first dose of the study drug

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: Cohort 1; Subject will receive MT-6548 on Day 1, 4, and 7. Subject will receive Iron supplement A on Day 1, 4, or 7. Subject will receive Iron supplement B on Day 1, 4, or 7.	Drug: MT-6548; Oral tablet; Other Names: AKB-6548; vadadustat; Drug: Iron supplement A; Oral tablet; Drug: Iron supplement B; Oral tablet
Experimental: Cohort 2; Subject will receive MT-6548 on Day 1 and 4. Subject will receive Iron supplement C on Day 1 or 4.	Drug: MT-6548; Oral tablet; Other Names: AKB-6548; vadadustat; Drug: Iron supplement C; Oral tablet
Experimental: Cohort 3; Subject will receive MT-6548 on Day 1 and 4. Subject will receive Iron supplement D on Day 1 or 4.	Drug: MT-6548; Oral tablet; Other Names: AKB-6548; vadadustat; Drug: Iron supplement D; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity(AUC0-∞) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Maximum Plasma Concentration (Cmax) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Area Under the Plasma Concentration-time Curve From Time Zero Until the Last Quantifiable Concentration (AUC0-last) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Mean Residence Time From Zero to Infinity (MRT0-∞) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Apparent Terminal Elimination Rate Constant (Kel) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)
Terminal Elimination Half-life (t1/2) of Unchanged MT-6548	Up to Day 8 (Cohort 1), Up to Day 5 (Cohort 2, 3)

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Study Director: General Manager, Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Kokado Y, Kawai K, Nanjo T, Kinoshita S, Kondo K. In Vitro and Clinical Pharmacokinetic Studies of the Effects of Iron-containing Agents on Vadadustat, an Oral Hypoxia-inducible Factor-Prolyl Hydroxylase Inhibitor. Clin Ther. 2021 Aug;43(8):1408-1418.e5. doi: 10.1016/j.clinthera.2021.06.013. Epub 2021 Sep 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2018
• Primary Completion (Actual): September 30, 2018
• Study Completion (Actual): September 30, 2018

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Trace Elements; Micronutrients; Iron
• Other Study ID Numbers: MT-6548-J05

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.: Yes