Table 1.
Summary of studies included in the population PK analysis
| Study | Phase | Participant status | Description | DRF dose | Diet (protocol-specified) | PK sample collection | AM/PM sampling |
|---|---|---|---|---|---|---|---|
| 001 | 1 | Healthy | Part 1: single dose | 49, 105, 210, 420, 630, 840, or 980 mg | Fasted 10 h before and 4 h after study drug | Serial up to 24 h | AM |
| 1 | Healthy | Part 2: DRF vs. DMF crossover | 420 mg | Fasted 10 h before and 4 h after study drug | Serial up to 12 h | AM | |
| A102 | 1 | Healthy | Part A: single-dose, crossover, food effect | 420 mg |
Fasted: 10 h before and 4 h after study drug Fed: fasted 10 h prior to high-fat/calorie meal consumed 30 min before study drug |
Serial up to 12 h | AM |
| 1 | Healthy | Part B: multiple dose |
210, 420, or 630 mg BID × 5 days |
Days 1 and 5: fasted 10 h before and 4 h after study drug Days 1–5: fasted 10 h before morning dose |
Day 1, day 5: serial up to 10 h Days 2, 3, 4: 10 h |
AM and PM | |
| A103 | 1 | Healthy | Single-dose crossover DRF vs. DMF |
DRF 462 mg DMF 240 mg |
Fasted 10 h before and 4 h after study drug | Serial up to 72 h | AM |
| A104 | 1 | Healthy | Single-dose crossover DRF vs. DMF |
DRF 462 mg DMF 240 mg |
Fasted 10 h prior to high-fat/calorie meal consumed 30 min before study drug | Serial up to 48 h | AM |
| A105 | 1 | Healthy | Period 1: unlabeled DRF single dose, mass balance | 462 mg |
Fasted 10 h before and 4 h after study drug |
Serial up to 120 h | AM |
| A106 | 1 | Healthy | 3-way crossover study with 5% or 40% alcohol | 462 mg | Fasted | Serial up to 72 h | AM |
| A108 | 1 | Renal impairment | Single dose | 462 mg |
Fasted 8 h before and 4 h after dose Light snack 2 h pre dose |
Serial up to 216 h | AM |
| A109 | 1 | Healthy |
Single dose, 4-way crossover food effect |
462 mg |
Fasted: 10 h before and 4 h after study drug Fed: low- or medium-fat/calorie meal consumed 30 min before drug, no food 4 h after study drug |
Serial up to 48 h | AM |
| A110 | 1 | Healthy | Multiple doses, QTc | 462 mg BID on days 2–5, QD day 6 | Fasted 10 h before and 4 h after drug | Day 6, day 11: serial up to 24 h | AM |
| 924 mg BID on days 7–10, QD day 11 | |||||||
| EVOLVE-MS-1 | 3 | Patients with MS | Open-label study up to 96 weeks |
De novo participants: 231 mg BID for week 1, then 462 mg BID Rollover participants: 462 mg BID |
Take on an empty stomach, at least 1 h before or 2 h after eating or drinking anything but water | Day 1, day 29: serial up to 8 h | AM |
| Day 15, day 57: pre and 2–3 h post | AM or PM | ||||||
| EVOLVE-MS-2 | 3 | Patients with MS |
DRF and DMFa Part A (exploratory) |
231 mg BID week 1 462 mg BID weeks 2–5 |
With or without food, avoid taking with a high-fat/calorie meal | Day 1, day 29: serial up to 8 h | AM |
| Days 15, day 36: pre and 2–3 h post | AM or PM |
AM morning dose, BID twice daily, DMF dimethyl fumarate, DRF diroximel fumarate, MS multiple sclerosis, PK pharmacokinetic, PM evening dose, QD single dose, QTc QT interval corrected for heart rate
aDMF dosing was 120 mg BID for week 1 and 240 mg BID for weeks 2–5