Study to Compare the Pharmacokinetics of Mycophenolate Mofetil Metabolites From Four Tablet Formulations in Healthy Participants

A Randomized, Open Label, Four-way Crossover Study to Compare the Pharmacokinetics of Mycophenolate Mofetil Metabolites From Four Tablet Formulations in Healthy Subjects

This is a single center, randomized, open label, 4-treatment, 4-period, 4-sequence, 4-way crossover study to compare the pharmacokinetics of mycophenolate mofetil (MMF) metabolites from 4 tablet formulations in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Renodapt; Drug: Mycept; Drug: Cellmune; Drug: CellCept

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand
    • Christchurch Clinical Studies Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

A body mass index (BMI) between 18 and 32 kilogram per meter square (kg/m^2)

Exclusion Criteria:

• Any evidence of clinically significant allergic, renal, cardiac, bronchopulmonary, vascular, gastro-intestinal, neurological, metabolic or immunodeficiency disorders, cancer, hepatitis or cirrhosis
• Any evidence of gall bladder surgery, surgery of the gastro-intestinal tract or any other medical condition considered likely to affect drug absorption
• Any major illness within 2 months prior to first dosing or febrile illness within 14 days prior to first dosing
• Any known history of clinically significant allergic reactions or drug hypersensitivity, especially hypersensitivity to MMF or mycophenolic acid (MPA)
• Any other ongoing concomitant disease or condition that could interfere with, or the treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participants
• Any prescribed or over-the-counter (OTC) medication, herbal medicine or dietary aid taken within 2 weeks before the first study drug dosing or within six times the elimination half-life of the medication before the first study drug dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Renodapt Then Mycept Then Cellmune Then CellCept; Participants will receive Renodapt in first treatment period (each treatment period= 3 days) followed by Mycept in second treatment period then Cellmune in third treatment period and CellCept in fourth treatment period. A washout period of 7 days will be separating each treatment period.	Drug: Renodapt; Renodapt will be administered as 500 milligrams (mg) tablet orally on Day 1 in any treatment periods.; Drug: Mycept; Mycept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: Cellmune; Cellmune will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: CellCept; CellCept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.
EXPERIMENTAL: Mycept Then CellCept Then Renodapt Then Cellmune; Participants will receive Mycept in first treatment period (each treatment period= 3 days) followed by CellCept in second treatment period then Renodapt in third treatment period and Cellmune in fourth treatment period. A washout period of 7 days will be separating each treatment period.	Drug: Renodapt; Renodapt will be administered as 500 milligrams (mg) tablet orally on Day 1 in any treatment periods.; Drug: Mycept; Mycept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: Cellmune; Cellmune will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: CellCept; CellCept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.
EXPERIMENTAL: Cellmune Then Renodapt Then CellCept Then Mycept; Participants will receive Cellmune in first treatment period (each treatment period= 3 days) followed by Renodapt in second treatment period then CellCept in third treatment period and Mycept in fourth treatment period. A washout period of 7 days will be separating each treatment period.	Drug: Renodapt; Renodapt will be administered as 500 milligrams (mg) tablet orally on Day 1 in any treatment periods.; Drug: Mycept; Mycept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: Cellmune; Cellmune will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: CellCept; CellCept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.
EXPERIMENTAL: CellCept Then Cellmune Then Mycept Then Renodapt; Participants will receive CellCept in first treatment period (each treatment period= 3 days) followed by Cellmune in second treatment period then Mycept in third treatment period and Renodapt in fourth treatment period. A washout period of 7 days will be separating each treatment period.	Drug: Renodapt; Renodapt will be administered as 500 milligrams (mg) tablet orally on Day 1 in any treatment periods.; Drug: Mycept; Mycept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: Cellmune; Cellmune will be administered as 500 mg tablet orally on Day 1 in any treatment periods.; Drug: CellCept; CellCept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Maximum Observed Plasma Concentration (Cmax) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Absorption Lag Time (Tlag) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Plasma Terminal Half-Life (t1/2) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Apparent Oral Clearance (CL/F) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Apparent Oral Volume of Distribution (V/F) of MPA	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
AUC (0-inf) of the Glucuronide Metabolite of MPA (MPAG)	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
AUClast of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Cmax of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Tmax of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Tlag of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
t1/2 of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
CL/F of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
V/F of MPAG	Predose (0.5 hours), and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose on Day 1
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to 9 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Reigner B, Grange S, Bentley D, Banken L, Abt M, Hughes R, Scheubel E, Guentert TW. Generics in transplantation medicine: Randomized comparison of innovator and substitution products containing mycophenolate mofetil . Int J Clin Pharmacol Ther. 2019 Oct;57(10):506-519. doi: 10.5414/CP203487.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: December 1, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (ESTIMATE): December 5, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): December 5, 2016
• Last Update Submitted That Met QC Criteria: December 1, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: WP21980

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO