Further study details as provided by Neuren Pharmaceuticals...

Further study details as provided by Neuren Pharmaceuticals Limited:
Primary Outcome Measures:
Adverse events [ Time Frame: Through to Day 42 ] [ Designated as safety issue: Yes ]Incidence of adverse events from randomization through to end of study drug administration (Day 28) and serious adverse events through to final follow-up assessment at Day 42.

Secondary Outcome Measures:
Change in EEG activity [ Time Frame: From baseline through to Day 42 ] [ Designated as safety issue: No ]Video EEG monitoring will assessed over a 4 hour awake period at baseline (pre-study drug), daily during up-titration through to Day 5, Days 11 and 23 (on maximal daily dose), and after treatment on Day 42. Data will be analysed for change in the number of spikes in the EEG per hour and absolute change in the power of frequency bands in the EEG over an hour.

Behavior [ Time Frame: Baseline through to Day 42 ] [ Designated as safety issue: No ]Changes in the frequency of the characteristic stereotypic hand movements will be calculated (via the VEEG recordings) between baseline (pre-study drug), during study drug administration (Days 1 thru 5, and Days 11 and 23), and after study drug administration (Day 42).

Physiological changes [ Time Frame: Baseline through to Day 42 ] [ Designated as safety issue: No ]Changes in autonomic function, i.e. respiratory rhythm, apneas, heart rate variation and cardiorespiratory coupling will be calculated between baseline (pre-study drug), during study drug administration (Days 1 thru 5, and Days 11 and 23), and after study drug administration on Day 42.

Global and Functional outcome Measures [ Time Frame: Baseline through to Day 42 ] [ Designated as safety issue: No ]
Global outcome as measured by the change in scores on the Rett Syndrome Clinical Severity Score, The Rett Syndrome Motor-Behavior Assessment Scale and the Clinical Global Impression - Severity and Improvement scales.
Changes in caregiver assessment of the top three causes for concern as captured via a Visual Analogue Scale will be calculated within subjects between baseline (pre-study drug), during study drug administration (Day 23), and after study drug administration (Day 42).
Changes in the Aberrant Behavior Checklist and Vineland Adaptive Behavior Scales will be calculated within subjects between baseline (pre-study drug), and during study drug administration (Day 23).

Other Outcome Measures:
Pharmacokinetics [ Time Frame: Baseline through to Day 42 ] [ Designated as safety issue: No ]The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax (peak), Cmin (trough), CAV at steady state. These parameters will be compared between dose groups for both mutation type groups.