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

NCT02981290 | Completed Phase 1

• 1 other identifier: WP21980
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• 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

Study Arms (4)

Renodapt Then Mycept Then Cellmune Then CellCept

EXPERIMENTAL

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; Drug: Mycept; Drug: Cellmune; Drug: CellCept

Mycept Then CellCept Then Renodapt Then Cellmune

EXPERIMENTAL

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; Drug: Mycept; Drug: Cellmune; Drug: CellCept

Cellmune Then Renodapt Then CellCept Then Mycept

EXPERIMENTAL

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; Drug: Mycept; Drug: Cellmune; Drug: CellCept

CellCept Then Cellmune Then Mycept Then Renodapt

EXPERIMENTAL

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; Drug: Mycept; Drug: Cellmune; Drug: CellCept

Interventions

Renodapt DRUG

Renodapt will be administered as 500 milligrams (mg) tablet orally on Day 1 in any treatment periods.

CellCept Then Cellmune Then Mycept Then Renodapt; Cellmune Then Renodapt Then CellCept Then Mycept; Mycept Then CellCept Then Renodapt Then Cellmune; Renodapt Then Mycept Then Cellmune Then CellCept

Mycept DRUG

Mycept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.

CellCept Then Cellmune Then Mycept Then Renodapt; Cellmune Then Renodapt Then CellCept Then Mycept; Mycept Then CellCept Then Renodapt Then Cellmune; Renodapt Then Mycept Then Cellmune Then CellCept

Cellmune DRUG

Cellmune will be administered as 500 mg tablet orally on Day 1 in any treatment periods.

CellCept Then Cellmune Then Mycept Then Renodapt; Cellmune Then Renodapt Then CellCept Then Mycept; Mycept Then CellCept Then Renodapt Then Cellmune; Renodapt Then Mycept Then Cellmune Then CellCept

CellCept DRUG

CellCept will be administered as 500 mg tablet orally on Day 1 in any treatment periods.

CellCept Then Cellmune Then Mycept Then Renodapt; Cellmune Then Renodapt Then CellCept Then Mycept; Mycept Then CellCept Then Renodapt Then Cellmune; Renodapt Then Mycept Then Cellmune Then CellCept

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Christchurch Clinical Studies Trust

Christchurch, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 31397274 DERIVED

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 5, 2016
• Study Start: July 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: December 5, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)