In view of the relatively high starting doses, it is not surprising that the combination MTD was established after a single dose escalation using a conventional 3+3 phase I study design.
In a single-dose escalation phase 1 trial, we observed a sifalimumab-specific and dose-dependent inhibition of the overexpression of type I interferon-inducible mRNAs in the blood of treated subjects.
The first part was a single fibre dose escalation study to establish how the extent of necrosis related to the delivered light dose and to choose a suitable light dose for the second, multifibre part of the study.
To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study.
Similar dose escalation studies were also reported previously (Holthuis et al, 1985; Fox et al, 1991), but they involved a single agent for dose escalation, in contrast to ours, which used a combination of two agents and their escalated doses.
As indicated by O'Dell, however, the costs of the strategies varied substantially between the groups and, as the clinical results for all groups were comparable at 2 years of therapy, one may argue to start with a single synthetic DMARD with escalation to biologics only in patients with persistent active disease.
A second bronchodilator may be considered in moderate COPD to optimise symptom benefit [ 1, 10] whilst avoiding the risk of side effects associated with dose escalation of a single bronchodilator [ 10].
The following antifungal agents were used either as the sole agent throughout the course of treatment, or in a sequential pattern resulting in the use of multiple agents for a single episode (that is, de-escalation): fluconazole was used most often (n = 21, 67.7%), followed by amphotericin B-based (BL/CL) preparations (n = 7, 22.6%), caspofungin (n = 6, 19.4%) and voriconazole (n = 4, 12.9%).
Dose escalation started with a single oral dose of 10 mg telatinib.
In their latest report, Takahashi et al. showed the preliminary results of a phase I/II trial as a dose escalation study using a single fraction [ 25].
