BP control maintained with relacorilant in patients with Cushing’s syndrome

Treatment with relacorilant in adult patients with endogenous hypercortisolism helps maintain blood pressure (BP) control, according to a phase III study.

Conducted at 77 study centres across 11 countries, the study included adult patients with endogenous hypercortisolism and hypertension, hyperglycaemia, or both. All participants had at least two clinical signs or symptoms of hypercortisolism.

In the open-label phase, patients received relacorilant, with dose increased from 100 mg up to 400 mg, for 22 weeks. Treatment was administered orally once daily. Patients who met response criteria were randomly assigned to either continue relacorilant 400 mg (or highest tolerated dose) or receive placebo for 12 weeks in the randomised-withdrawal phase.

The primary outcome was the lost hypertension response at week 12 during the randomised-withdrawal phase. This outcome was evaluated in all patients who received at least one dose of study drug. Safety was also assessed.

A total of 152 patients were enrolled in the study, of whom 95 completed the open-label relacorilant phase. Sixty-two patients met response criteria and were randomly allocated to the relacorilant arm (n=30; mean age 46.6 years, 73 percent female) or the placebo arm (n=32; mean age 48.8 years, 81 percent female). There were 21 and 22 patients in the respective groups who met the hypertension response criteria.

The primary outcome occurred with significantly less frequency in the relacorilant vs the placebo arm (proportion difference 34 percent; odds ratio, 0.17, 95 percent confidence interval, 0.04–0.77; p=0.022).

In the randomised-withdrawal phase safety population, the most common adverse in the relacorilant and placebo arms were back pain (17 percent vs 19 percent), acne (10 percent vs 0), arthralgia (10 percent vs 9 percent), bursitis (10 percent vs 0), headache (10 percent vs 13 percent), and insomnia (0 vs 13 percent). None of the patients in either treatment arm had excessive glucocorticoid receptor antagonism, adrenal insufficiency, vaginal bleeding associated with endometrial hypertrophy, drug-induced hypokalaemia, or drug-induced QT interval prolongation.

The present data position relacorilant as a potential therapeutic option to reduce the harmful and debilitating effects of endogenous hypercortisolism.