In the COMACS study children were assigned to dosing strata on the basis of pre-trial dose levels.
This was an open-label, dose-escalation phase I trial; three dose levels were planned for aflibercept: (a) 2 mg kg−1, (b) 4 mg kg, and (c) 6 mg kg−1.
Based on the phase I trials, two dose levels were selected for Phase II/III studies: 250 and 500 mg day−1.
The simulated trial uses six dose levels with prior toxicity probabilities noted above.
The clinical trial used three dose levels of PXT-3003 in 80 adults with mild to moderate CMT1A.
We tested this alternative FU/IRI-based regimen in a phase I trial, evaluating three dose levels of IRI and two of FU in a 3-weekly schedule.
After the toxicity outcome of each patient is observed, we terminate the trial if both dose levels are toxic and close the higher dose arm if only the higher dose is toxic.
A dose response relationship was established in a double-blind phase II trial at three dose levels of 0.3, 3, or 10 mg kg−1, administered every 3 weeks for four doses, followed by 12-weekly maintenance therapy.
For example, the first scenario in the original paper is a trial testing six dose levels, with prior toxicity probabilities of 0.05, 0.1, 0.2, 0.3, 0.5 and 0.7 respectively, and a target toxicity probability of 0.20.
Idenix announced late Thursday that gastrointestinal toxicity observed in some patients participating in a Phase IIb trial prompted the company to modify the trial; patient dosing levels were cut from 800 milligrams per day to 200 milligrams or 400 milligrams.
