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Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design.
Considering these challenges, we developed a general nanosuspension formulation that minimized organic co-solvent, was easy to prepare and was applicable to an IV infusion or multiple dose study.
A selected formulation given once‐daily was further evaluated against the commercial enteric tablet dosed twice‐daily in a multiple dose study, and shown to provide desired nearly constant therapeutic plasma concentrations over the entire 24‐h dosing interval.
To validate this hypothesis and the therapeutic potential of the LNA ASO, a multiple dose study with weekly dosing of 5 mg/kg of the 13-mer LNA antisense oligonucleotide was conducted.
The phase I trial was an open-label, single and multiple dose study, with accelerated, toxicity-guided dose escalation [ 26].
Although baseline cortisol levels remained normal, all patients treated at 500 and 800 mg in the multiple dose study developed an abnormal response to a short Synacthen test by Day 11.
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These were GCP-compliant, single and multiple dose studies of PK/PD and tolerability in healthy volunteers and postmenopausal women.
The maximum tolerated dose of 6 mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.
But efficacy, tolerability, and safety need to be tested in more trials and more patients, perhaps especially in multiple dose studies that capture more information than a single dose efficacy study can do.
However, prior to translation of these findings to the clinical arena, multiple dose studies are required.
If multiple dose studies are carried out, the radiopharmaceutical is administered weeks apart and, from a toxicological stand-point, is, therefore, considered equivalent to a single dose.
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