A new Phase 3 clinical trial (NCT02697734) is actively recruiting Cushing’s disease patients in several countries to test the safety and effectiveness of the investigational therapy osilodrostat (LCI699).
The 48-week, multicenter, randomized, double-blind, placebo-controlled study is sponsored by Novartis Pharmaceuticals. Estimated enrollment is 69 patients at 26 locations in 11 countries, including the U.S.
High levels of the hormone cortisol, detected in blood and urine samples, is the underlying mechanism of Cushing’s disease. The investigational treatment osilodrostat is an orally active inhibitor of 11-beta-hydroxylase, the enzyme that controls the last phase of cortisol biosynthesis in the adrenal cortex.
Osilodrostat showed promising results in a Phase 2 trial (NCT01331239) in patients with Cushing’s disease.
Osilodrostat is similar to a therapy previously used to treat Cushing’s called Metopirone (metyrapone), but with stronger inhibitory activity and a longer plasma half-life, an indicator of the longevity of a drug determined by measuring the amount of time required for the drug to be eliminated from plasma.
In the Phase 3 trial, patients with a confirmed diagnosis of persistent or recurrent Cushing’s disease will be randomly assigned to receive osilodrostat or a placebo. The first part of this trial lasts 12 weeks. Both osilodrostat and the placebo will be administered orally to patients in increasing doses of 1 mg, 5 mg, 10 mg, and 20 mg.
After 12 weeks, patients in both groups will receive osilodrostat until week 48. After that, patients can choose to continue receiving osilodrostat for up to 100 weeks.
The trial’s primary outcome is to determine the percentage of randomized participants with a complete response at week 12, assessed as having urine free cortisol levels below the upper limit of the normal range. Secondary measures include a complete response rate by week 36, the percentage change in mean urine free cortisol, and the time to first control of urine free cortisol. Health-related quality of life also will be assessed at baseline and at weeks 12, 36, and 48.
Data from completion and assessment of the primary outcome is scheduled to be available in November 2019.
Information on recruitment and eligibility can be found here.