Randomized, double-blind (for clazosentan), placebo- and moxifloxacin-controlled, 3-way cross-over Phase 1 study to assess the effect of two intravenous doses of clazosentan on the QTc interval duration in healthy subjects

When bleeding occurs in the brain, the brain tissue responds by contracting the
blood vessels near the bleeding. This cramping of
blood vessels can result in local brain cells receiving not enough blood. The
brain areas that receive too little blood may in turn die.
Clazosentan is being developed to prevent and/or reverse cramping of blood
vessels after a stroke.

This study aims at investigating potential relevant QT effects of clazosentan
at supra therapeutic doses in healthy male and female subjects using a
concentration/response analysis approach in compliance with the ICH E14
guidance [FDA 2017].

Primary objective:
To assess potential QT liability of clazosentan at two supra-therapeutic i.v.
doses.

Secondary objectives:
To assess the safety and tolerability of clazosentan at supra-therapeutic
doses.
To investigate the PK of clazosentan.
To ensure assay sensitivity using concentration/QT analysis with moxifloxacin.
To assess the effect of clazosentan on heart rate (HR), PR and QRS intervals,
T-wave morphology, and U-wave presence.

This is a single-center, randomized, double-blind (for clazosentan), placebo-
and moxifloxacin-controlled, 3-way cross-over, study to investigate the effect
of clazosentan on the duration of the QT interval in healthy male and female
subjects.

The study will start with a screening. At the screening a physical examination
will take place and a few other standard
medical assessments will be performed (ECG,vital signs). Furthermore a blood
and urine sample will be taken for
laboratory tests and an alcohol breathtest and drug screen will be done.

All subjects will receive a continuous infusion of either clazosentan
(Treatment A, doses of 20 and 60 mg/h, 3 h each), placebo for 6 h (Treatment
B), and moxifloxacin (400 mg oral, Treatment C) immediately followed by
clazosentan placebo i.v. for 6 h. Subjects will be randomly assigned to one of
the 6 treatment sequences. On several time points blood will be taken, Holter
ECG will be measured, and urine will be collected . The subjects will be asked
for possible side effects on regular basis. Furthermore several safety
assessments will be done frequently.

Finally, a end of study visit will take place and a follow-up phone call will
take place .

The risk to health at the chosen dose is limited, but the volunteers may
experience any of the side effects written in the ICF or
symptoms that have not reported before.

Volunteers health is closely monitored during the study to minimize these
risks.