Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers

Phase 4

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: BG00012 (DMF) (Tecfidera®.)

• Registration Number: NCT02683863
• Lead Sponsor: Multiple Sclerosis Center of Northeastern New York

Brief Summary

The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. PK samples (pharmacokinetics - or the amount of study drug in blood) will be tested to compare with PK samples, the amount of study drug, in spinal fluid (CSF).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-08
• Study First Submitted: 2016-01-14
• Study First Submitted QC: 2016-02-11
• Study First Posted: 2016-02-17
• Primary Completion: 2017-01-31
• Study Completion: 2017-01-31
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-21
• Last Update Posted: 2017-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 4	BG00012 (DMF) (Tecfidera®.)	4. Four subjects for predose CSF samples
Group 1	BG00012 (DMF) (Tecfidera®.)	There will be 4 CSF sampling groups at the Week 6 visit for PK assessment: 1. Four subject for CSF samples 3 hours after dosing
Group 2	BG00012 (DMF) (Tecfidera®.)	2. Four subjects for CSF samples 5 hours after dosing
Group 3	BG00012 (DMF) (Tecfidera®.)	3. Four subjects for CSF samples 7 hours after dosing

Primary Outcome Measures

Name	Time	Method
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS.	post-DMF treatment in Week 6	Concentration of DMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in plasma in subjects with SPMS.	treatment in week 6	Concentration of DMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of MMF(the primary metabolite of study drug) in CSF with SPMS.	treatment in week 6	Concentration of MMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) in plasma in subjects with SPMS.	treatment in week 6	Concentration of MMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in CSF with SPMS.	treatment in week 6	Concentration of DMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in plasma in subjects with SPMS.	treatment in week 6	Concentration of DMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
The primary objective of the study is to investigate the PK (drug level) of MMF (the primary metabolite of study drug) conjugate in CSF with SPMS.	treatment in week 6	Concentration of MMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) conjugate in plasma in subjects with SPMS.	treatment in week 6	Concentration of MMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6

Secondary Outcome Measures

Name	Time	Method
A secondary objective is to assess the effects of DMF on RNA samples from CSF cellular pellet for transcriptionomics in the CSF of subjects with SPMS.	at 28 weeks	RNA samples from CSF cellular pellet for transcriptionomics.
A secondary objective is to assess the effects of DMF on PD biomarkers downstream of Nrf2 in the CSF of subjects with SPMS.	at 28 weeks	PD biomarkers downstream of Nrf2, such as NAD(P)H hydrogenase \[quinone 1\], heme oxygenase-1, and aldo-keto reductase family 1 member B8 that have not been evaluated in CNS.
A secondary objective is to assess the effects of DMF on biomarkers of inflammation in the CSF of subjects with SPMS.	at 28 weeks	Biomarkers of inflammation (e.g., osteopontin, B cell activating factor, chemokines, and matrix metalloproteinase 9), which may reflect pathogenesis in SPMS.
A secondary objective is to assess the effects of DMF on biomarkers of neuroaxonal damage in the CSF of subjects with SPMS.	at 28 weeks	Biomarkers of neuroaxonal damage (e.g., neurofilament, myelin basic protein, glial fibrillary acidic protein, and neural cell adhesion molecule), which may reflect pathogenesis in SPMS.
A secondary objective is to assess the effects of DMF on biomarkers of oxidative stress in the CSF of subjects with SPMS.	at 28 weeks	Biomarkers of oxidative stress (e.g., myeloperoxidase, 8-Oxo-2'-deoxyguanosine and RNA biomarkers), which may reflect pathogenesis in SPMS
A secondary objective is to assess the effects of DMF on myelin lipid biomarkers in the CSF of subjects with SPMS.	at 28 weeks	Myelin lipid biomarkers (e.g., cholesterol, galactoceramide, sulfatides, and sphingomyelin), which may correlate with disability progression in MS patients.
A secondary objective is to assess the effects of DMF on pharmacogenomic biomarkers in the CSF of subjects with SPMS.	at 28 weeks	Pharmacogenomic biomarkers: DNA analysis from blood samples.

Trial Locations

Locations (1)

Multiple Sclerosis Center of Northeastern New York; 🇺🇸 Latham, New York, United States