Clinical trial NCT02981290: Study to Compare the Pharmacokinetics of Mycophenolate Mofetil Metabolites From Four Tablet Formulations in Healthy Participants
Official title: A Randomized, Open Label, Four-way Crossover Study to Compare the Pharmacokinetics of Mycophenolate Mofetil Metabolites From Four Tablet Formulations in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-12-05
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of MPA
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of MPA
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of MPA
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of MPA
timeFrame: 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
measure: Absorption Lag Time (Tlag) of MPA
timeFrame: 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
measure: Plasma Terminal Half-Life (t1/2) of MPA
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) of MPA
timeFrame: 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:
measure: Apparent Oral Volume of Distribution (V/F) of MPA
timeFrame: 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
measure: AUC (0-inf) of the Glucuronide Metabolite of MPA (MPAG)
timeFrame: 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
measure: AUClast of MPAG
timeFrame: 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
measure: Cmax of MPAG
timeFrame: 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
measure: Tmax of MPAG
timeFrame: 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
measure: Tlag of MPAG
timeFrame: 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
measure: t1/2 of MPAG
timeFrame: 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
measure: CL/F of MPAG
timeFrame: 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
measure: V/F of MPAG
timeFrame: 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
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 9 weeks
Other outcomes:
Locations:
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.