Clinical trial: Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease (NCT02180217)

Eligibility criteria:
Inclusion Criteria:

          1. Written informed consent must be obtained before any assessment is performed.

          2. Male or female patients aged 18 - 75 years.

          3. Patients must have confirmed Cushing's disease that is persistent or recurrent.

          4. Patients with a history of prior pituitary surgery must be at least 30 days
             post-surgery to be eligible for inclusion in this study.

          5. Patients that received glucocorticoid replacement therapy post-operatively must have
             discontinued such therapy for at least one week, or 5 half-lives, whichever is longer,
             prior to screening.

          6. Patients with de novo Cushing's disease can be included only if they are not
             considered candidates for surgery.

          7. Patients with a history of pituitary irradiation can be included, provided that at
             least 2 years (stereotactic radiosurgery) or 3 years (conventional radiation) have
             elapsed from the time of last radiation treatment to the time of enrollment into this
             study.

          8. Patients are permitted to washout current drug therapy to meet these entry criteria if
             they have a known diagnosis of Cushing's disease.

        Exclusion Criteria:

          1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half lives at the time of enrollment, whichever is longer; or longer if required by
             local regulations, and for any other limitation of participation in an investigational
             trial based on local regulations.

          2. History of hypersensitivity to LCI699 or to drugs of similar chemical classes.

          3. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases.

          4. Patients with risk factors for QTc prolongation or Torsade de Pointes.

          5. Pregnant or nursing (lactating) women.

          6. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing and for 1 week after completion of dosing.

          7. Patients with compression of the optic chiasm due to a macroadenoma or patients at
             high risk of compression of the optic chiasm (tumor within 2 mm of optic chiasm).

          8. Patients who have a known inherited syndrome as the cause for hormone over secretion.

          9. Patients with Cushing's syndrome due to ectopic ACTH secretion or ACTH-independent
             (adrenal) Cushing's syndrome.

         10. Patients who have undergone major surgery within 1 month prior to screening.

         11. Hypertensive patients with uncontrolled blood pressure.

         12. Diabetic patients with poorly controlled diabetes.

         13. Patients who are not euthyroid as judged by the investigator.

         14. Patients who have a history of: congestive heart failure, unstable angina, sustained
             ventricular tachycardia, clinically significant bradycardia, advanced heart block,
             acute MI less than one year prior to study entry, or clinically significant impairment
             in cardiovascular function.

         15. Patients with moderate to severe renal impairment.

         16. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic
             persistent hepatitis, or patients with defined elevated ALT/ AST/ Bilirubin.

         17. Patients who have any current or prior medical condition that can interfere with the
             conduct of the study or the evaluation of its results in the opinion of the
             investigator or the sponsor's medical monitor.

         18. Patients who have a history of alcohol or drug abuse in the 6 month period prior to
             study treatment.

         19. Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will be unable to complete the entire study.
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.
Subject must be at most 75 Years

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