Clinical trial: A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome. (NCT03277690)

Eligibility criteria:
INCLUSION CRITERIA:

        SONICS STUDY COMPLETERS:

        Completed the final SONICS visit (M12) and have demonstrated maintenance of clinical
        response on a stable Therapeutic Dose of levoketoconazole for at least 12 weeks prior to
        study entry.

        ALL OTHERS:

          -  Confirmed newly diagnosed, persistent or recurrent endogenous Cushing's syndrome of
             any etiology, except secondary to malignancy (including pituitary or adrenal
             carcinoma).

          -  Elevated mean 24-hour UFC levels at least 1.5X upper limit of the normative range of
             the study's central laboratory assay and from a minimum of three measurements from
             adequately collected urine.

          -  Presence of abnormal values from at least one of these two diagnostic tests:

               -  Abnormal Dexamethasone Suppression Test (DST) OR

               -  Elevated late night salivary cortisol concentrations (at least two measurements)
                  each greater than the upper limit of the study's central laboratory normative
                  range

          -  Non-candidates for CS-specific surgery, refuse surgery or surgery will be delayed
             until after study completion and agree to complete this study prior to surgery.

          -  If post-surgical for CS-specific surgery, then no significant post-operative sequelae
             remain and the risk of such sequelae is considered negligible.

        EXCLUSION CRITERIA:

        Subjects will be excluded from the study if ANY of the following criteria are met (NOTE:
        exclusion criteria apply to and must be assessed in both cohorts):

          -  Enrolled in SONICS but have not completed SONICS through Visit M12.

          -  Pseudo-Cushing's syndrome based on assessment of the Investigator.

          -  Cyclic Cushing's syndrome with multi-week periods of apparent spontaneous CS
             remission.

          -  Non-endogenous source of hypercortisolism, including pharmacological corticosteroids
             or ACTH.

          -  Radiotherapy of any modality directed against the source of hypercortisolism within
             the last 5 years.

          -  Treatment with mitotane within 6 months of enrollment.

          -  History of malignancy, including adrenal or pituitary carcinomas (other than low-risk,
             well-differentiated carcinomas of thyroid, breast or prostate that are very unlikely
             to require further treatment in the opinion of the treating physician, or squamous
             cell or basal cell carcinoma of the skin).

          -  Clinical or radiological signs of compression of the optic chiasm.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the office due to weight gain and fatigue.  He is not able to lift heavy objects or climb stairs. Family history is positive for DM type 2 and HTN in his father.  Blood pressure is 165/90 mm Hg and pulse is 85/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 138 mg/dL and 24-hour urinary cortisol is twice the upper normal limit.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal. This patient's findings are consistent with endogenous Cushing Syndrome.

Patient description (patient's own words): I'm a 47-year-old man. I went to the clinic because I had been gaining weight and had increased fatigue over the past few weeks. I was not able to lift heavy objects or even climb the stairs. My dad was diagnosed with type 2 diabetes and high blood pressure. During the exam, they took my blood pressure, which was 165/90 mm Hg, and my pulse was 85/min. They found out that I have weaknesses in both of my arms and legs. I also did a blood test on an empty stomach, and I had a glucose level of 138 mg/dL, and twice the upper normal limit of cortisol. I had high-normal levels of ACTH. The doctor said I suffer from endogenous Cushing Syndrome.

Does the patient match the trial criteria? Entailment