Phase 2
N=12
Safety and Efficacy of LCI699 in Cushing's Disease Patients
Cushings Disease · Cushing Disease
Bottom Line
View on ClinicalTrials.gov: NCT01331239 ↗Enrolled (actual)
12
Serious AEs
22.6%
Results posted
Jan 2021
Primary outcome: Primary: Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 — 100.0 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LCI699 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 |
100.0 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall) |
292.8; 188.0; 6957.8; 3670.0; 2523.1; 1743.0 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall) |
4.21; 5.48; 45.48; 54.75; 15.32; 9.03 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4) |
165.5; 127.0; -151.1; -64.5; -101.9; -120.0 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female) |
209.60; 307.23; -42.19; -24.63; 10.55; -141.00 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male) |
55.00; 77.10; 35.00; 18.30; -1.00; 110.10 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female) |
9.09; 2.43; 14.89; 2.90; 3.58; 3.20 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male) |
5.88; 5.80; -1.20; -5.20; -1.80; -5.80 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin |
23.706; 73.973; 45.899; -16.838; 70.051; -55.638 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1 |
157.56; 235.30; -9.78; -35.20; -41.23; -113.43 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female) |
2.78; 1.00; 7.45; 4.40; 7.47; 2.63 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male) |
2.48; 5.90; 0.48; -5.70; -0.53; -5.90 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female) |
1.18; 1.43; 1.85; 5.27; 0.53; 0.50 | — |
| SECONDARY Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male) |
7.53; 7.10; 6.55; 2.40; 5.17; 32.60 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose |
108.1; 96.3; -14.5; -16.3; -22.5; -20.8 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin) |
5.7; 6.0; -0.1; -0.3; -0.1; -0.6 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides |
5.2; 5.7; -0.7; -0.5; -0.1; -1.2 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP) |
84.5; 87.3; 0.8; 2.6; -3.4; -5.8 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight |
85.4; 84.0; -2.1; 0.6; -5.2; -3.2 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI) |
30.6; 31.3; -0.7; 0.2; -1.9; -1.4 | — |
| SECONDARY Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI) |
0.3; 0.3; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Pharmacokinetics (PK) Parameters: Area Under Curve (AUC)0-6h ss, AUC0-12h ss |
37.79; 94.21; 236.83; NA; NA; 69.96 | — |
| SECONDARY PK Parameters: Cmax ss, Ctrough ss |
8.76; 23.09; 59.17; NA; NA; 2.73 | — |
| SECONDARY PK Parameters: Tmax ss, |
1.50; 1.50; 1.26; NA; NA | — |
| SECONDARY PK Parameters: T1/2 ss, |
6.39; 3.54; 4.32; NA; NA | — |
| SECONDARY Percentage of Participants Who Were Responders on 24-hour Urine Free Cortisol (UFC) at Week 22 |
80.0; 75.0; 80.0; 75.0; 0; 0 | — |
| SECONDARY Number of Participants With Escape |
2; 0 | — |
Summary
This exploratory study is a proof of concept study to determine whether LCI699 can safely reduce the level of urinary free cortisol in patients with Cushing's disease.
In addition, this study evaluated the long term efficacy and safety of LCI699 including an additional 12 week of treatment followed by a 12 month long term optional extension.
A second extension provided patients who were clinically benefitting from LCI699 an opportunity to continue to have access to the drug until LCI699 was commercially available and reimbursed or through the availability of a local access program.
Eligibility Criteria
Inclusion Criteria
- Patients with a confirmed diagnosis of Cushing's Disease (persistent or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH.
- Patients with de novo Cushing's disease can be included only if they are not considered candidate for surgery
Exclusion Criteria
- Patients treated with mitotane 6 months prior to Visit 1
- Patients with compression of the optic chiasm
- Patients with a known inherited syndrome as the cause for hormone over secretion
- Patients with Cushing's syndrome due to ectopic ACTH secretion or adrenal Cushing's syndrome
- Patients with pseudo-Cushing's syndrome
- Patients who are not biochemically euthyroid
- Diabetic patients with poorly controlled diabetes (HbA1c >9%)
- 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.
- Patients who have received pituitary irradiation within five years prior to Visit 1.
- Patients with risk factors for QTc prolongation or Torsade de Pointes.
Data sourced from ClinicalTrials.gov (NCT01331239). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.