Clinical trial: Open-label Treatment in Cushing's Syndrome (NCT03621280)

Eligibility criteria:
Inclusion Criteria:

          1. Completed the Extended Evaluation Phase of Study COR-2012-01 (i.e. M12)

          2. Completed the Restoration Phase of Study COR-2017-01 (i.e. RES2)

             NOTE: Subjects meeting criteria 1 or 2 above who have had a break in therapy may be
             eligible only after discussion with the Medical Monitor. If eligible, such subjects
             may require re-establishment of the Therapeutic Dose via titration. All subjects who
             have had a break in therapy should be discussed with the Medical Monitor to determine
             the starting dose of levoketoconazole. Prior to resuming treatment with
             levoketoconazole, other therapies for Cushing's Syndrome must undergo an appropriate
             washout period, with minimum durations as follows:

               -  Ketoconazole or metyrapone: 2 weeks;

               -  Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks);

               -  Octreotide acetate LAR, lanreotide Autogel, pasireotide LAR: 12 weeks;

               -  Lanreotide SR: 8 weeks;

               -  Octreotide acetate (immediate release) or short-acting pasireotide: 1 week;

               -  Mifepristone (RU 486, KORLYM): 4 weeks;

               -  Megestrol acetate or medroxyprogesterone acetate (and selected other synthetic
                  progestins): 6 weeks.

          3. Currently in a named patient program or other Expanded Access Program receiving
             levoketoconazole

          4. Were levoketoconazole-naïve prior to entry and received early rescue therapy with
             open-label levoketoconazole in Study COR-2017-01.

          5. Achieved a clinically meaningful partial response (with reduction of UFC) in Study
             COR-2017-01 at dose level 7 or at a maximally tolerated dose of levoketoconazole but
             did not meet the randomization criteria for Study COR-2017-01 at the end of the Dose
             Titration and Maintenance Phase when randomization was open.

          6. Were levoketoconazole-naïve prior to entry and were enrolled in Study COR-2017-01 in
             the Dose Titration and Maintenance Phase when randomization was closed. (NOTE: Such
             subjects must receive at least 1 dose of levoketoconazole before transitioning to this
             study.)

        Exclusion Criteria:

          1. Discontinued levoketoconazole while participating in Study COR-2012-01 or Study
             COR-2017-01 or a named patient program or other Expanded Access program, due to safety
             or tolerability concerns or lack of efficacy.

          2. Scheduled for surgery for treatment of CS or received surgery for treatment of CS
             within the 6 weeks prior to Screening.

          3. Treated with mitotane within 6 months prior to enrollment.

          4. 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).
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? 0