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Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02180217
Recruitment Status : Completed
First Posted : July 2, 2014
Results First Posted : June 16, 2020
Last Update Posted : January 6, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Sequential Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cushings Disease
Interventions Drug: osilodrostat
Drug: LCI699 matching placebo
Enrollment 137
Recruitment Details 132 patients were planned, 137 were enrolled and 137 were analyzed.
Pre-assignment Details  
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period. Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period. All participants in this group took open label osilodrostat, before and after randomization.
Period Title: Overall Study
Started 36 35 66
Discontinued at/Prior to Week 12 (W12) 0 0 7
Discont. at/Prior to W26 But After W12 0 0 12
Discontinued Prior to W48 But After W26 0 2 3
Completed Week 48 (Core Phase) 36 33 44
Completed W48, Did Not Enter Ext. Phase 1 3 3
Completed W48, Entered Ext. Phase 35 30 41
Discontinued Extension Phase 12 6 16
Completed Ext. Phase 23 24 25
Completed [1] 24 27 28
Not Completed 12 8 38
Reason Not Completed
Adverse Event             3             2             22
Death             1             1             0
Withdrawal by Subject             1             1             4
Subject/Guardian decision             5             3             6
Physician Decision             1             1             6
Unsatisfactory therapeutic effect             1             0             0
[1]
Completed = Completed Core/Extension Phase
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized Total
Hide Arm/Group Description Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period. Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period. All participants in this group took open label osilodrostat, before and after randomization. Total of all reporting groups
Overall Number of Baseline Participants 36 35 66 137
Hide Baseline Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 35 participants 66 participants 137 participants
44.3  (11.27) 42.0  (13.47) 39.0  (13.38) 41.2  (12.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 66 participants 137 participants
Female
30
  83.3%
22
  62.9%
54
  81.8%
106
  77.4%
Male
6
  16.7%
13
  37.1%
12
  18.2%
31
  22.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 66 participants 137 participants
Caucasian 27 23 39 89
Black 0 3 1 4
Asian 7 7 25 39
Other 2 2 1 5
1.Primary Outcome
Title Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata
Hide Description To compare the complete response rate at the end of the 8-week period of randomized withdrawal between randomized patients.A primary efficacy responder is defined as a randomized patient who has mUFC ≤ ULN at Week 34 and who was neither discontinued (study or RW treatment) nor had osilodrostat dose increase above the level at Week 26 during the RW Period of the study. mUFC: mean urinary free cortisol; ULN: Upper Limit of Normal
Time Frame Week 34 (8 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized analysis set (RAS): comprises all randomized patients who received at least one dose of randomized drug (osilodrostat or placebo).
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
Overall Number of Participants Analyzed 36 34
Measure Type: Number
Unit of Measure: Percentage of participants
86.1 29.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Osilodrostat (LCI699), LCI699 Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 13.71
Confidence Interval (2-Sided) 95%
3.73 to 53.44
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Secondary Efficacy Responder at Week 24 (Key Secondary Endpoint)
Hide Description To assess the complete response rate at the end of individual dose-titration and treatment with LCI699 in the initial single-arm, open label period. A Key secondary efficacy responder is defined as a patient in FAS who has mUFC ≤ ULN at Week 24 and the dose of osilodrostat during Study Period 2 (Weeks 13-24) was not increased above the level established at the end of Study Period 1 (Week 12). Patients who had missing mUFC assessment at Week 24 will be counted as non-responders for the key secondary endpoint.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title All Participants
Hide Arm/Group Description:
Consisted of all participants who were enrolled and treated in the open label osilodrostat.
Overall Number of Participants Analyzed 137
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
52.6
(43.9 to 61.1)
3.Secondary Outcome
Title Time-to-loss of Control of Mean Urinary Free Cortisol (mUFC) by Randomized Treatment Group
Hide Description Time-to-loss of control of mUFC during the RW Period, defined as the time (in days) from randomization to the first evidence of loss of control (defined as mUFC assessment >1.5 ULN based on central laboratory result & at least 2 of the associated individual urine samples showing UFC >1.5×ULN) within the RW period. A patient without evidence of loss of control was censored at the date of the last assessment with mUFC ≤ 1.5 ULN. If a patient discontinued randomized treatment without having a UFC assessment, they were censored at the date of randomization. The measure type (number) refers to an Event probability estimate 8 weeks after randomization.
Time Frame 8 weeks after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized analysis set (RAS): comprised all randomized patients who received at least one dose of randomized drug (osilodrostat or placebo).
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
Overall Number of Participants Analyzed 36 34
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
5.6
(1.4 to 20.4)
61.1
(45.0 to 77.5)
4.Secondary Outcome
Title Complete Response Rate (CRR)
Hide Description Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN
Time Frame Week 12, Week 24, Week 48, Week 72, last observed value
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 Number Analyzed 36 participants 35 participants 66 participants
86.1 91.4 53.0
Week 24 Number Analyzed 36 participants 35 participants 66 participants
100.0 97.1 34.8
Week 48 Number Analyzed 36 participants 35 participants 66 participants
88.9 77.1 48.5
Week 72 Number Analyzed 35 participants 30 participants 41 participants
82.9 83.3 78.0
Last observed value Number Analyzed 36 participants 35 participants 66 participants
69.4 74.3 53.0
5.Secondary Outcome
Title Actual Change From Baseline in mUFC
Hide Description Actual change in mUFC from baseline.
Time Frame Weeks 12, 24, 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: nmol/24h
Actual Baseline (BL) Number Analyzed 36 participants 35 participants 66 participants
890.0  (1275.66) 560.0  (548.84) 1305.8  (2012.21)
Wk 12: Act. change from BL Number Analyzed 33 participants 34 participants 58 participants
-848.4  (1335.66) -510.3  (556.84) -1021.3  (1825.55)
Wk 24: Act. change from BL Number Analyzed 36 participants 35 participants 54 participants
-821.2  (1283.03) -485.5  (558.99) -930.3  (1778.04)
Wk 48: Act. change from BL Number Analyzed 34 participants 32 participants 42 participants
-708.2  (983.14) -477.1  (529.04) -1189.9  (2042.48)
Wk 72: Act. change from BL Number Analyzed 32 participants 29 participants 35 participants
-680.7  (1003.63) -536.7  (585.78) -826.7  (1684.92)
Last avail. assess.: Act. change from BL Number Analyzed 36 participants 35 participants 66 participants
-795.2  (1286.22) -387.3  (605.63) -893.4  (1969.56)
6.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Fasting Glucose
Hide Description Actual change in fasting glucose from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Number Analyzed 34 participants 33 participants 62 participants
102.7  (35.23) 90.5  (18.53) 101.8  (31.00)
Wk 48 Number Analyzed 33 participants 30 participants 38 participants
-7.9  (32.24) -5.5  (12.13) -14.1  (22.66)
Wk 72 Number Analyzed 30 participants 25 participants 32 participants
-0.5  (16.84) -4.4  (15.13) -10.8  (24.02)
Last avail. assessment Number Analyzed 34 participants 32 participants 62 participants
-8.6  (37.05) -0.6  (21.00) -15.6  (26.62)
7.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Hemoglobin A1C (HbA1C)
Hide Description Actual change in glycosylated hemoglobin (HbA1c) from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: percentage
Baseline Number Analyzed 36 participants 35 participants 66 participants
6.1  (0.98) 5.8  (0.93) 6.0  (0.97)
Wk 48 Number Analyzed 35 participants 33 participants 42 participants
-0.3  (0.86) -0.4  (0.56) -0.4  (0.65)
Wk 72 Number Analyzed 33 participants 29 participants 35 participants
-0.4  (0.66) -0.4  (0.47) -0.4  (0.64)
Last avail. assessment Number Analyzed 36 participants 35 participants 66 participants
-0.3  (0.78) -0.2  (0.47) -0.3  (0.68)
8.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride
Hide Description Actual change in Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: mmol/L
Cholesterol: BL Number Analyzed 36 participants 34 participants 66 participants
5.5  (1.22) 5.3  (0.90) 5.1  (1.24)
Cholesterol: Wk 48 Number Analyzed 35 participants 32 participants 41 participants
-0.7  (0.87) -0.4  (0.89) -0.5  (0.90)
Cholesterol: Wk 72 Number Analyzed 33 participants 27 participants 33 participants
-0.4  (0.96) -0.3  (0.75) -0.4  (0.98)
Cholesterol: Last avail. assessment Number Analyzed 36 participants 34 participants 66 participants
-0.3  (1.16) -0.3  (1.03) -0.4  (1.15)
LDL Cholesterol: BL Number Analyzed 36 participants 34 participants 66 participants
3.2  (1.09) 3.1  (0.77) 2.9  (0.94)
LDL Cholesterol: Wk 48 Number Analyzed 35 participants 32 participants 40 participants
-0.3  (0.75) -0.2  (0.74) -0.1  (0.82)
LDL Cholesterol: Wk 72 Number Analyzed 33 participants 27 participants 33 participants
-0.2  (0.77) -0.2  (0.66) -0.1  (0.86)
LDL Cholesterol: Last avail asses Number Analyzed 36 participants 34 participants 65 participants
-0.1  (0.98) -0.2  (0.88) -0.1  (0.99)
HDL Cholesterol: BL Number Analyzed 36 participants 34 participants 66 participants
1.7  (0.55) 1.5  (0.36) 1.6  (0.42)
HDL Cholesterol: Wk 48 Number Analyzed 35 participants 32 participants 41 participants
-0.3  (0.39) -0.2  (0.17) -0.3  (0.28)
HDL Cholesterol: Wk 72 Number Analyzed 33 participants 27 participants 33 participants
-0.2  (0.39) -0.2  (0.27) -0.3  (0.28)
HDL Cholesterol: Last avail assess Number Analyzed 36 participants 34 participants 66 participants
-0.2  (0.40) -0.1  (0.27) -0.2  (0.34)
Triglyceride: BL Number Analyzed 36 participants 34 participants 66 participants
1.5  (0.78) 1.4  (0.62) 1.6  (1.74)
Triglyceride: Wk 48 Number Analyzed 35 participants 32 participants 41 participants
-0.1  (0.49) 0.0  (0.54) 0.0  (1.22)
Triglyceride: Wk 72 Number Analyzed 33 participants 28 participants 33 participants
0.0  (0.57) -0.1  (0.67) 0.0  (0.60)
Triglyceride: Last avail. assess Number Analyzed 36 participants 34 participants 66 participants
0.0  (0.64) -0.1  (0.75) 0.1  (1.48)
9.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Sitting Systolic Blood Pressure (SBP) & Sitting Diastolic Blood Pressure (DBP)
Hide Description Actual change in sitting SBP & DBP from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: mmHg
SBP: Baseline Number Analyzed 36 participants 35 participants 66 participants
132.2  (15.44) 128.8  (11.93) 134.0  (16.34)
SBP: Wk 48 Number Analyzed 35 participants 33 participants 43 participants
-15.2  (17.00) -4.8  (12.28) -9.2  (15.48)
SBP: Wk 72 Number Analyzed 34 participants 29 participants 36 participants
-12.2  (15.90) -8.2  (19.41) -9.4  (19.08)
SBP: Last avail. assessment Number Analyzed 36 participants 35 participants 66 participants
-8.2  (15.25) -4.6  (15.20) -10.8  (15.31)
DBP: Baseline Number Analyzed 36 participants 35 participants 66 participants
85.3  (11.38) 85.0  (10.03) 85.4  (10.53)
DBP: Wk 48 Number Analyzed 35 participants 33 participants 43 participants
-7.8  (11.63) -5.1  (9.66) -6.0  (11.79)
DBP: Wk 72 Number Analyzed 34 participants 29 participants 36 participants
-5.9  (11.17) -7.0  (10.33) -4.8  (12.26)
DBP: Last avail. assessment Number Analyzed 36 participants 35 participants 66 participants
-3.4  (11.79) -3.5  (11.50) -5.0  (10.45)
10.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Weight
Hide Description Actual change in weight from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: kg
Baseline Number Analyzed 36 participants 35 participants 66 participants
78.2  (19.02) 83.4  (24.73) 80.7  (23.06)
Wk 48 Number Analyzed 36 participants 33 participants 43 participants
-3.4  (5.64) -3.9  (5.77) -4.0  (5.82)
Wk 72 Number Analyzed 34 participants 29 participants 36 participants
-3.7  (6.93) -5.0  (6.03) -5.6  (6.75)
Last avail. assessment Number Analyzed 36 participants 35 participants 66 participants
-2.9  (8.28) -3.7  (11.13) -4.2  (6.35)
11.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Body Mass Index (BMI)
Hide Description Actual change in BMI from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Baseline Number Analyzed 36 participants 35 participants 66 participants
29.6  (7.36) 30.9  (8.38) 30.4  (7.74)
Wk 48 Number Analyzed 36 participants 33 participants 43 participants
-1.3  (2.22) -1.5  (2.12) -1.5  (2.17)
Wk 72 Number Analyzed 34 participants 29 participants 36 participants
-1.4  (2.79) -1.8  (2.14) -2.0  (2.55)
Last avail. assessment Number Analyzed 36 participants 35 participants 66 participants
-1.2  (3.34) -1.5  (3.94) -1.6  (2.41)
12.Secondary Outcome
Title Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Waist Circumference
Hide Description Actual change in waist circumference from baseline.
Time Frame Baseline, Weeks 48, 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: cm
Baseline Number Analyzed 35 participants 33 participants 65 participants
100.5  (16.81) 103.7  (18.26) 105.0  (21.15)
Wk 48 Number Analyzed 34 participants 32 participants 43 participants
-5.1  (6.26) -4.2  (10.12) -4.7  (7.07)
Wk 72 Number Analyzed 33 participants 29 participants 36 participants
-5.1  (7.18) -6.1  (9.86) -7.4  (8.53)
Last avail. assessment Number Analyzed 35 participants 33 participants 65 participants
-4.7  (10.05) -5.2  (12.24) -6.2  (9.96)
13.Secondary Outcome
Title Actual Change From Baseline in Patient-Reported Outcomes (Cushing's Health-Related Quality of Life (QoL)) - Total Score
Hide Description Cushing's Disease Health-Related Quality of Life Questionnaire was developed to evaluate quality of life in patients with Cushing's syndrome. It is comprised of 12 items that capture patient responses on 7 concepts: daily activities, healing & pain, mood & self-confidence, social concerns, physical appearance, memory & concern about the future. These items are measured on a 5- point Likert-type scale assessing how often or how much each item has been related to the patient's Cushing's disease in the previous 4 weeks. The raw score is calculated by summing the individual item scores prior to being standardized so that the total score ranges from 0 to 100. Content reliability, sensitivity to change & psychometric properties have been validated in patients with Cushing's disease. Patients were asked to complete the questionnaire prior to clinical assessments being undertaken. Increases from baseline are indicative of an improvement.
Time Frame Baseline, Week (W) 48, W72, Last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline Number Analyzed 36 participants 35 participants 66 participants
44.4  (18.33) 43.2  (22.45) 40.5  (17.61)
Week 48 Number Analyzed 35 participants 32 participants 43 participants
16.1  (15.15) 10.2  (16.57) 13.2  (17.79)
Week 72 Number Analyzed 32 participants 28 participants 37 participants
15.8  (16.08) 12.6  (20.68) 16.3  (21.31)
Last available assess. Number Analyzed 36 participants 35 participants 65 participants
16.1  (15.99) 11.8  (20.51) 12.9  (18.91)
14.Secondary Outcome
Title Actual Change From Baseline in Patient-Reported Outcomes: Beck Depression Inventory-II (BDI-II)
Hide Description BDI-II is a patient-reported instrument developed to measure the severity of depression in adults & adolescents aged 13 years & older. It is designed to be completed by the patient on paper & takes approximately 5 minutes to complete. The BDI-II consists of 21 items designed to assess the intensity of depression in clinical & normal patients in the preceding 2 weeks. Items are rated on a 4-point severity scale of 0 ('not at all') to 3 ('extreme' form of each symptom) with differing response options for each item. A global score ranging from 0 to 63 is calculated with a higher score representing a greater level of depression. The following scoring guidelines for interpretation of BDI-II have been suggested (Smarr, 2011): Minimal range =0-13, Mild depression =14-19, Moderate depression =20-28 and Severe depression = 29-63. Patients were asked to complete the questionnaire prior to clinical assessments being undertaken. A reduction from baseline in BDI-II is indicative of an improvement.
Time Frame Baseline, W48, W72, Last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: scores on a a scale
Baseline Number Analyzed 36 participants 35 participants 66 participants
15.1  (11.14) 17.8  (9.93) 17.3  (10.67)
W48 Number Analyzed 35 participants 32 participants 43 participants
-4.8  (9.84) -5.3  (7.99) -7.0  (10.17)
W72 Number Analyzed 32 participants 28 participants 36 participants
-6.0  (9.55) -4.6  (9.41) -9.0  (12.34)
Last avail. assess. Number Analyzed 36 participants 35 participants 65 participants
-6.2  (9.93) -5.0  (9.49) -4.9  (10.66)
15.Secondary Outcome
Title Actual Change in Patient-Reported Outcomes: EQ-5D-5L Utility Index
Hide Description The EQ-5D-5L questionnaire is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. It is cognitively undemanding, taking only a few minutes to complete. Instructions to respondents are included in the questionnaire. The EQ-5D-5L measures 5 items on mobility, self-care, usual activities, pain/discomfort, anxiety/depression, measured on 5 levels: no problems, slight problems, moderate problems, severe problems, & extreme problems. A utility index can be computed from the EQ 5D-5L descriptive system with utility scores ranging from -0.281 (worst imaginable health state) to 1 (best imaginable health state), with -0.281 representing an "unconscious" health state. A single index value is analyzed for the EQ-5D-5L score. An increase from baseline in the EQ-ED-5L utility index is indicative of an improvement.
Time Frame Baseline, W48, W72, Last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline Number Analyzed 36 participants 35 participants 66 participants
0.7  (0.24) 0.7  (0.24) 0.7  (0.28)
Week 48 Number Analyzed 35 participants 32 participants 43 participants
0.1  (0.18) 0  (0.25) 0.1  (0.18)
Week 72 Number Analyzed 32 participants 28 participants 36 participants
0.1  (0.18) 0.1  (0.26) 0.1  (0.19)
Last avail. assess. Number Analyzed 36 participants 35 participants 65 participants
0.1  (0.22) 0  (0.28) 0.1  (0.23)
16.Secondary Outcome
Title Actual Change in Patient-Reported Outcomes: EQ-5D-5L Vascular Analog Scale (VAS)
Hide Description The EQ-5D-5L also includes a 20 cm vertical, VAS (visual analogue scale) with on a scale of 0-100, with endpoints labeled 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. A single index value is analyzed for the VAS score. An increase from baseline in the EQ-ED-5L VAS is indicative of an improvement.
Time Frame Baseline, W48, W72, Last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline Number Analyzed 36 participants 35 participants 66 participants
61.3  (18.97) 64.2  (16.37) 60.8  (21.09)
Week 48 Number Analyzed 35 participants 31 participants 43 participants
12.6  (20.64) 6.9  (12.56) 9.7  (17.16)
Week 72 Number Analyzed 32 participants 27 participants 36 participants
11.2  (18.98) 6.6  (15.47) 10.1  (19.80)
Last avail. assess. Number Analyzed 36 participants 34 participants 65 participants
12.1  (19.71) 6.4  (18.65) 6.2  (20.42)
17.Secondary Outcome
Title Change From Baseline in the Physical Features of Cushing's Disease by Photography
Hide Description Improvement from baseline to Weeks 48, 72 and End of Treatment (Extension period) in each of the following clinical signs of Cushing's disease by photography: facial rubor, hirsutism, striae, supraclavicular fat pad, dorsal fat pad, proximal muscle wasting (atrophy), central (abdominal) obesity, and ecchymoses (bruises).
Time Frame Week 48, Week 72, Last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
W48: Facial rubor Number Analyzed 30 participants 30 participants 37 participants
50.0
(31.3 to 68.7)
46.7
(28.3 to 65.7)
43.2
(27.1 to 60.5)
W48: Striae Number Analyzed 30 participants 30 participants 37 participants
30.0
(14.7 to 49.4)
23.3
(9.9 to 42.3)
40.5
(24.8 to 57.9)
W48:Supraclavicular fat pad Number Analyzed 30 participants 30 participants 37 participants
56.7
(37.4 to 74.5)
43.3
(25.5 to 62.6)
54.1
(36.9 to 70.5)
W48: Dorsal fat pad Number Analyzed 30 participants 30 participants 37 participants
60.0
(40.6 to 77.3)
40.0
(22.7 to 59.4)
56.8
(39.5 to 72.9)
W48: Proximal muscle atrophy Number Analyzed 30 participants 30 participants 37 participants
40.0
(22.7 to 59.4)
26.7
(12.3 to 45.9)
45.9
(29.5 to 63.1)
W48: Central obesity Number Analyzed 30 participants 30 participants 37 participants
43.3
(25.5 to 62.6)
30.0
(14.7 to 49.4)
51.4
(34.4 to 68.1)
W48: Ecchymoses Number Analyzed 30 participants 30 participants 37 participants
33.3
(17.3 to 52.8)
26.7
(12.3 to 45.9)
43.2
(27.1 to 60.5)
W72: Facial rubor Number Analyzed 29 participants 27 participants 30 participants
48.3
(29.4 to 67.5)
55.6
(35.3 to 74.5)
53.3
(34.3 to 71.7)
W72: Striae Number Analyzed 29 participants 27 participants 30 participants
27.6
(12.7 to 47.2)
25.9
(11.1 to 46.3)
36.7
(19.9 to 56.1)
W72:Supraclavicular fat pad Number Analyzed 29 participants 27 participants 30 participants
55.2
(35.7 to 73.6)
51.9
(31.9 to 71.3)
53.3
(34.3 to 71.1)
W72: Dorsal fat pad Number Analyzed 29 participants 27 participants 30 participants
69.0
(49.2 to 84.7)
48.1
(28.7 to 68.1)
53.3
(34.3 to 71.7)
W72: Proximal muscle atrophy Number Analyzed 29 participants 27 participants 30 participants
31.0
(15.3 to 50.8)
25.9
(11.1 to 46.3)
46.7
(28.3 to 65.7)
W72: Central obesity Number Analyzed 29 participants 27 participants 30 participants
37.9
(20.7 to 57.7)
37.0
(19.4 to 57.6)
43.3
(25.5 to 62.6)
W72: Ecchymoses Number Analyzed 29 participants 27 participants 30 participants
27.6
(12.7 to 47.2)
29.6
(13.8 to 50.2)
36.7
(19.9 to 56.1)
End of Trial (EOT):Facial rubor Number Analyzed 25 participants 23 participants 26 participants
60.0
(38.7 to 78.9)
56.5
(34.5 to 76.8)
53.8
(33.4 to 73.4)
EOT: Striae Number Analyzed 25 participants 23 participants 26 participants
32.0
(14.9 to 53.5)
34.8
(16.4 to 57.3)
30.8
(14.3 to 51.8)
EOT:Supraclavicular fat pad Number Analyzed 25 participants 23 participants 26 participants
52.0
(31.3 to 72.2)
43.5
(23.2 to 65.5)
42.3
(23.4 to 63.1)
EOT: Dorsal fat pad Number Analyzed 25 participants 23 participants 26 participants
56.0
(34.9 to 75.6)
52.2
(30.6 to 73.2)
46.2
(26.6 to 66.6)
EOT: Proximal muscle atrophy Number Analyzed 25 participants 23 participants 26 participants
36.0
(18.0 to 57.5)
21.7
(7.5 to 43.7)
50.0
(29.9 to 70.1)
EOT: Central obesity Number Analyzed 25 participants 23 participants 26 participants
40.0
(21.1 to 61.3)
39.1
(19.7 to 61.5)
38.5
(20.0 to 59.4)
EOT: Ecchymoses Number Analyzed 25 participants 23 participants 26 participants
28.0
(12.1 to 49.4)
39.1
(19.7 to 61.5)
38.5
(20.2 to 59.4)
18.Secondary Outcome
Title Change From Baseline in Bone Mineral Density - All Participants
Hide Description Actual change from baseline to Week 48 and the LOV in bone mineral density as measured by DXA scan at the lumbar spine and total hip. An increase in bone mineral density is indicative of an improvement..
Time Frame Baseline, Week 48, Last observed value (LOV)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Mean (Standard Error)
Unit of Measure: g/cm2
Baseline (L1-L4 Lumbar Spine) Number Analyzed 28 participants 27 participants 58 participants
1.0  (0.20) 1.0  (0.17) 1.0  (0.18)
W48 (L1-L4 Lumbar Spine) Number Analyzed 23 participants 23 participants 35 participants
1.0  (0.19) 1.0  (0.17) 1.0  (0.19)
LOV (L1-L4 Lumbar Spine) Number Analyzed 26 participants 24 participants 46 participants
1.0  (0.20) 1.0  (0.18) 1.0  (0.18)
Baseline (Total Hip) Number Analyzed 29 participants 26 participants 58 participants
0.9  (0.18) 0.8  (0.15) 0.9  (0.16)
W48 (Total Hip) Number Analyzed 24 participants 21 participants 35 participants
0.9  (0.17) 0.8  (0.14) 0.9  (0.16)
LOV (Total Hip) Number Analyzed 27 participants 22 participants 46 participants
0.9  (0.17) 0.8  (0.13) 0.9  (0.16)
19.Secondary Outcome
Title Time-to-escape
Hide Description Escape was defined as the time (in days) from the first mUFC ≤ ULN to the first mUFC results > 1.5 x ULN with at least 2 individual UFC results > 1.5 x ULN the loss happened beyond 12-week dose titration period. Participants randomized to placebo were not included in the analysis.
Time Frame From the first mUFC ≤ ULN to the first mUFC results > 1.5 x ULN with at least 2 individual UFC results > 1.5 x ULN
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat. This is a subset of the FAS participants who met all the criteria for Escape. The placebo patients + patients that did not reach mUFC <= ULN at some stage during the study are excluded from the denominator.
Arm/Group Title All Participants
Hide Arm/Group Description:
Consisted of all participants in the study under osilodrostat treatment
Overall Number of Participants Analyzed 97
Median (95% Confidence Interval)
Unit of Measure: days
546.0
(212.0 to 968.0)
20.Secondary Outcome
Title LCI699 Exposures
Hide Description To evaluate exposures of LCI699 in patients with Cushing's disease. Plasma concentrations (predose, 0.75 h, 1.5 h, and 4 h post-dose) of LCI699. These are the maximum number of PAS subjects analyzed for each incident dose.
Time Frame from week 2 to 10 at Predose, 0.75h, 1.5h, and 4h post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis set (PAS) consists of all enrolled patients who receive at least one dose of osilodrostat and have at least one evaluable post-dosing PK assessment.
Arm/Group Title Osilodrostat (LCI699) 2 mg Osilodrostat (LCI699) 3 mg Osilodrostat (LCI699) 5 mg Osilodrostat (LCI699) 7 mg
Hide Arm/Group Description:
Participants received 2mg of osilodrostat
Participants received 3mg of osilodrostat
Participants received 5 mg of osilodrostat
Participants received 7 mg of osilodrostat
Overall Number of Participants Analyzed 132 39 105 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Week (Wk) 2: Predose Number Analyzed 79 participants 0 participants 0 participants 0 participants
1.904
(110.4%)
Wk 2: 0.75h Number Analyzed 14 participants 0 participants 0 participants 0 participants
1.907
(132.5%)
Wk 2: 1.5h Number Analyzed 3 participants 0 participants 0 participants 0 participants
5.1
(62.7%)
Wk 2: 4h Number Analyzed 18 participants 0 participants 0 participants 0 participants
5.818
(66.3%)
Wk 4: Predose Number Analyzed 50 participants 2 participants 31 participants 0 participants
2.104
(108.0%)
2.898
(109.1%)
3.584
(126.3%)
Wk 4: 0.75h Number Analyzed 2 participants 0 participants 9 participants 0 participants
0.859
(254.3%)
7.091
(137.8%)
Wk 4: 1.5h Number Analyzed 2 participants 0 participants 1 participants 0 participants
8.737
(3.6%)
24.2 [1] 
(NA%)
Wk 4: 4h Number Analyzed 1 participants 0 participants 9 participants 0 participants
8.930 [1] 
(NA%)
15.985
(48.3%)
Wk 6: Predose Number Analyzed 17 participants 3 participants 46 participants 2 participants
2.037
(63.5%)
2.392
(285.6%)
5.087
(122.9%)
8.065
(8.6%)
Wk 6: 0.75h Number Analyzed 1 participants 0 participants 5 participants 0 participants
3.110 [1] 
(NA%)
5.223
(229.4%)
Wk 6: 1.5h Number Analyzed 0 participants 1 participants 1 participants 0 participants
22.4 [1] 
(NA%)
21.4 [1] 
(NA%)
Wk 6: 4h Number Analyzed 1 participants 1 participants 5 participants 0 participants
8.380 [1] 
(NA%)
18.6 [1] 
(NA%)
18.373
(36.5%)
Wk 8: Predose Number Analyzed 13 participants 5 participants 35 participants 3 participants
2.198
(108.9%)
4.061
(67.4%)
4.487
(106.9%)
6.718
(34.2%)
Wk 8: 0.75h Number Analyzed 0 participants 0 participants 0 participants 0 participants
Wk 8: 1.5h Number Analyzed 1 participants 1 participants 0 participants 1 participants
10.8 [1] 
(NA%)
20.4 [1] 
(NA%)
32.1 [2] 
(NA%)
Wk 8: 4h Number Analyzed 1 participants 0 participants 0 participants 1 participants
6.65 [1] 
(NA%)
32 [2] 
(NA%)
Wk 10: Predose Number Analyzed 10 participants 9 participants 29 participants 6 participants
1.862
(128.9%)
3.007
(64.8%)
4.704
(106.8%)
5.451
(93.1%)
Wk 10: 0.75h Number Analyzed 0 participants 1 participants 0 participants 1 participants
6.7 [2] 
(NA%)
17.1 [2] 
(NA%)
Wk 10: 1.5h Number Analyzed 1 participants 1 participants 1 participants 0 participants
12.1 [1] 
(NA%)
18.3 [1] 
(NA%)
34.2 [1] 
(NA%)
Wk 10: 4h Number Analyzed 0 participants 1 participants 1 participants 1 participants
15.8 [1] 
(NA%)
27.2 [1] 
(NA%)
35.5 [1] 
(NA%)
[1]
NA: CV% geo-mean could not be calculated with just 1 patient
[2]
NA: CV% geo-mean could not be calculated with just 1 patient.
21.Secondary Outcome
Title Percentage of Participants With Complete Response Rate (CRR)
Hide Description Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN.
Time Frame Week 12, Week 24, Week 48, Week 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 Number Analyzed 36 participants 35 participants 66 participants
6.1 91.4 53.0
Week 24 Number Analyzed 36 participants 35 participants 66 participants
100 97.1 34.8
Week 48 Number Analyzed 36 participants 35 participants 66 participants
88.9 77.1 48.5
Week 72 Number Analyzed 35 participants 30 participants 41 participants
82.9 83.3 78.0
Last available assess. Number Analyzed 36 participants 35 participants 66 participants
69.4 74.3 53.0
22.Secondary Outcome
Title Percentage of Participants With Partial Response Rate (PRR)
Hide Description Partial response rate is defined as percentage of enrolled participants with ≥ 50% reduction from baseline in mUFC, but mUFC>ULN)
Time Frame Week 12, Week 24, Week 48, Week 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 Number Analyzed 36 participants 35 participants 66 participants
2.8 5.7 24.2
Week 24 Number Analyzed 36 participants 35 participants 66 participants
0.0 0.0 30.3
Week 48 Number Analyzed 36 participants 35 participants 66 participants
5.6 11.4 10.6
Week 72 Number Analyzed 35 participants 30 participants 41 participants
8.6 13.3 2.4
Last available assess. Number Analyzed 36 participants 35 participants 66 participants
22.2 11.4 22.7
23.Secondary Outcome
Title Percentage of Participants With Overall Response Rate (ORR)
Hide Description Overall response rate is defined as percentage of enrolled participants with mUFC ≤ ULN or at least 50% reduction from baseline.
Time Frame Week 12, Week 24, Week 48, Week 72, last available assessment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprised all enrolled patients who received at least one dose of osilodrostat.
Arm/Group Title Osilodrostat (LCI699) LCI699 Placebo Non-randomized
Hide Arm/Group Description:
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
All participants in this group took open label osilodrostat, before and after randomization.
Overall Number of Participants Analyzed 36 35 66
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 Number Analyzed 36 participants 35 participants 66 participants
88.9 97.1 77.3
Week 24 Number Analyzed 36 participants 35 participants 66 participants
100 97.1 65.2
Week 48 Number Analyzed 36 participants 35 participants 66 participants
94.4 88.6 59.1
Week 72 Number Analyzed 35 participants 30 participants 41 participants
91.4 96.7 80.5
Last available assess. Number Analyzed 36 participants 35 participants 66 participants
91.7 85.7 75.8
Time Frame Adverse Event (AE) timeframe: Adverse events were collected from first dose of study treatment until 30 days after the last dose administration, up to maximum duration of about 245.1 weeks.
Adverse Event Reporting Description Adverse Event: Any sign or symptom that occurs during the study treatment plus up to 30 days after the last dose administration.
 
Arm/Group Title Osilodrostat LCI699 Placebo Non-randomized All Participants
Hide Arm/Group Description Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period. Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period. All participants in this group took open label osilodrostat, before and after randomization. Consisted of all participants who were enrolled and treated with open label osilodrostat.
All-Cause Mortality
Osilodrostat LCI699 Placebo Non-randomized All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/36 (2.78%)   1/35 (2.86%)   0/66 (0.00%)   2/137 (1.46%) 
Hide Serious Adverse Events
Osilodrostat LCI699 Placebo Non-randomized All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/36 (36.11%)   10/35 (28.57%)   32/66 (48.48%)   55/137 (40.15%) 
Blood and lymphatic system disorders         
Anaemia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Autoimmune neutropenia  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Lymphadenopathy  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Neutropenia  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Cardiac disorders         
Cardiopulmonary failure  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Endocrine disorders         
Adrenal insufficiency  1  1/36 (2.78%)  1/35 (2.86%)  6/66 (9.09%)  8/137 (5.84%) 
Adrenocortical insufficiency acute  1  1/36 (2.78%)  0/35 (0.00%)  3/66 (4.55%)  4/137 (2.92%) 
Glucocorticoid deficiency  1  0/36 (0.00%)  0/35 (0.00%)  2/66 (3.03%)  2/137 (1.46%) 
Inappropriate antidiuretic hormone secretion  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pituitary infarction  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pituitary-dependent Cushing's syndrome  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Eye disorders         
Diplopia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Visual impairment  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Gastrointestinal disorders         
Abdominal pain  1  1/36 (2.78%)  1/35 (2.86%)  1/66 (1.52%)  3/137 (2.19%) 
Gastritis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Nausea  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pancreatitis acute  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Vomiting  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
General disorders         
Chills  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Influenza like illness  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Non-cardiac chest pain  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Pain  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Pyrexia  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Hepatobiliary disorders         
Cholecystitis  1  0/36 (0.00%)  1/35 (2.86%)  1/66 (1.52%)  2/137 (1.46%) 
Cholelithiasis  1  1/36 (2.78%)  0/35 (0.00%)  1/66 (1.52%)  2/137 (1.46%) 
Immune system disorders         
Anaphylactic shock  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Infections and infestations         
Cellulitis  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Chronic sinusitis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Gastroenteritis  1  0/36 (0.00%)  1/35 (2.86%)  3/66 (4.55%)  4/137 (2.92%) 
Gastroenteritis viral  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Influenza  1  1/36 (2.78%)  0/35 (0.00%)  2/66 (3.03%)  3/137 (2.19%) 
Keratitis fungal  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pneumonia  1  0/36 (0.00%)  1/35 (2.86%)  1/66 (1.52%)  2/137 (1.46%) 
Urinary tract infection  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Injury, poisoning and procedural complications         
Head injury  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Overdose  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Procedural headache  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Investigations         
Haemoglobin decreased  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Transaminases increased  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Dehydration  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Hypercalcaemia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Hypokalaemia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Hyponatraemia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Musculoskeletal and connective tissue disorders         
Foot deformity  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Groin pain  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pain in extremity  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Malignant pituitary tumour  1  0/36 (0.00%)  0/35 (0.00%)  2/66 (3.03%)  2/137 (1.46%) 
Metastases to liver  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pituitary tumour  1  1/36 (2.78%)  1/35 (2.86%)  4/66 (6.06%)  6/137 (4.38%) 
Pituitary tumour benign  1  1/36 (2.78%)  0/35 (0.00%)  2/66 (3.03%)  3/137 (2.19%) 
Tumour invasion  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Nervous system disorders         
Cranial nerve disorder  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Headache  1  0/36 (0.00%)  1/35 (2.86%)  2/66 (3.03%)  3/137 (2.19%) 
Idiopathic intracranial hypertension  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Migraine  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Seizure  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Syncope  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
VIth nerve paralysis  1  0/36 (0.00%)  0/35 (0.00%)  3/66 (4.55%)  3/137 (2.19%) 
Pregnancy, puerperium and perinatal conditions         
Unintended pregnancy  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Psychiatric disorders         
Anxiety  1  1/36 (2.78%)  1/35 (2.86%)  0/66 (0.00%)  2/137 (1.46%) 
Completed suicide  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Depression  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Suicidal ideation  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Renal and urinary disorders         
Acute kidney injury  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Cystitis glandularis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Reproductive system and breast disorders         
Metrorrhagia  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Uterine polyp  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Vaginal haemorrhage  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Dyspnoea  1  0/36 (0.00%)  1/35 (2.86%)  0/66 (0.00%)  1/137 (0.73%) 
Epistaxis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Pulmonary oedema  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Respiratory disorder  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Respiratory failure  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Vocal cord polyp  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Skin and subcutaneous tissue disorders         
Hidradenitis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
Urticaria  1  1/36 (2.78%)  0/35 (0.00%)  0/66 (0.00%)  1/137 (0.73%) 
Vascular disorders         
Venous thrombosis  1  0/36 (0.00%)  0/35 (0.00%)  1/66 (1.52%)  1/137 (0.73%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Osilodrostat LCI699 Placebo Non-randomized All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/36 (94.44%)   35/35 (100.00%)   65/66 (98.48%)   134/137 (97.81%) 
Blood and lymphatic system disorders         
Anaemia  1  4/36 (11.11%)  5/35 (14.29%)  6/66 (9.09%)  15/137 (10.95%) 
Cardiac disorders         
Bundle branch block right  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Tachycardia  1  2/36 (5.56%)  3/35 (8.57%)  3/66 (4.55%)  8/137 (5.84%) 
Ear and labyrinth disorders         
Ear pain  1  2/36 (5.56%)  0/35 (0.00%)  1/66 (1.52%)  3/137 (2.19%) 
Endocrine disorders         
Adrenal insufficiency  1  7/36 (19.44%)  10/35 (28.57%)  17/66 (25.76%)  34/137 (24.82%) 
Glucocorticoid deficiency  1  10/36 (27.78%)  9/35 (25.71%)  8/66 (12.12%)  27/137 (19.71%) 
Eye disorders         
Dry eye  1  2/36 (5.56%)  0/35 (0.00%)  2/66 (3.03%)  4/137 (2.92%) 
Eye pruritus  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Photophobia  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Vision blurred  1  0/36 (0.00%)  0/35 (0.00%)  4/66 (6.06%)  4/137 (2.92%) 
Gastrointestinal disorders         
Abdominal distension  1  2/36 (5.56%)  1/35 (2.86%)  3/66 (4.55%)  6/137 (4.38%) 
Abdominal pain  1  5/36 (13.89%)  2/35 (5.71%)  8/66 (12.12%)  15/137 (10.95%) 
Abdominal pain upper  1  3/36 (8.33%)  3/35 (8.57%)  3/66 (4.55%)  9/137 (6.57%) 
Constipation  1  4/36 (11.11%)  1/35 (2.86%)  5/66 (7.58%)  10/137 (7.30%) 
Dental caries  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Diarrhoea  1  5/36 (13.89%)  8/35 (22.86%)  14/66 (21.21%)  27/137 (19.71%) 
Dry mouth  1  0/36 (0.00%)  0/35 (0.00%)  4/66 (6.06%)  4/137 (2.92%) 
Dyspepsia  1  2/36 (5.56%)  5/35 (14.29%)  8/66 (12.12%)  15/137 (10.95%) 
Gastrooesophageal reflux disease  1  1/36 (2.78%)  2/35 (5.71%)  1/66 (1.52%)  4/137 (2.92%) 
Nausea  1  17/36 (47.22%)  11/35 (31.43%)  34/66 (51.52%)  62/137 (45.26%) 
Toothache  1  2/36 (5.56%)  0/35 (0.00%)  3/66 (4.55%)  5/137 (3.65%) 
Vomiting  1  7/36 (19.44%)  5/35 (14.29%)  21/66 (31.82%)  33/137 (24.09%) 
General disorders         
Application site rash  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Asthenia  1  11/36 (30.56%)  5/35 (14.29%)  11/66 (16.67%)  27/137 (19.71%) 
Chest discomfort  1  1/36 (2.78%)  0/35 (0.00%)  4/66 (6.06%)  5/137 (3.65%) 
Chills  1  1/36 (2.78%)  3/35 (8.57%)  2/66 (3.03%)  6/137 (4.38%) 
Fatigue  1  8/36 (22.22%)  13/35 (37.14%)  24/66 (36.36%)  45/137 (32.85%) 
Gait disturbance  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Influenza like illness  1  0/36 (0.00%)  2/35 (5.71%)  1/66 (1.52%)  3/137 (2.19%) 
Malaise  1  1/36 (2.78%)  2/35 (5.71%)  7/66 (10.61%)  10/137 (7.30%) 
Oedema  1  1/36 (2.78%)  3/35 (8.57%)  5/66 (7.58%)  9/137 (6.57%) 
Oedema peripheral  1  8/36 (22.22%)  5/35 (14.29%)  9/66 (13.64%)  22/137 (16.06%) 
Pain  1  2/36 (5.56%)  3/35 (8.57%)  1/66 (1.52%)  6/137 (4.38%) 
Pyrexia  1  4/36 (11.11%)  3/35 (8.57%)  13/66 (19.70%)  20/137 (14.60%) 
Immune system disorders         
Seasonal allergy  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Infections and infestations         
Bronchitis  1  1/36 (2.78%)  1/35 (2.86%)  6/66 (9.09%)  8/137 (5.84%) 
Cystitis  1  3/36 (8.33%)  2/35 (5.71%)  1/66 (1.52%)  6/137 (4.38%) 
Folliculitis  1  1/36 (2.78%)  2/35 (5.71%)  0/66 (0.00%)  3/137 (2.19%) 
Fungal skin infection  1  1/36 (2.78%)  2/35 (5.71%)  0/66 (0.00%)  3/137 (2.19%) 
Gastroenteritis  1  4/36 (11.11%)  3/35 (8.57%)  5/66 (7.58%)  12/137 (8.76%) 
Gastroenteritis viral  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Hordeolum  1  0/36 (0.00%)  3/35 (8.57%)  2/66 (3.03%)  5/137 (3.65%) 
Influenza  1  5/36 (13.89%)  8/35 (22.86%)  10/66 (15.15%)  23/137 (16.79%) 
Nasopharyngitis  1  9/36 (25.00%)  11/35 (31.43%)  13/66 (19.70%)  33/137 (24.09%) 
Sinusitis  1  3/36 (8.33%)  1/35 (2.86%)  4/66 (6.06%)  8/137 (5.84%) 
Tooth abscess  1  2/36 (5.56%)  1/35 (2.86%)  0/66 (0.00%)  3/137 (2.19%) 
Upper respiratory tract infection  1  2/36 (5.56%)  5/35 (14.29%)  7/66 (10.61%)  14/137 (10.22%) 
Urinary tract infection  1  6/36 (16.67%)  4/35 (11.43%)  14/66 (21.21%)  24/137 (17.52%) 
Injury, poisoning and procedural complications         
Contusion  1  1/36 (2.78%)  2/35 (5.71%)  4/66 (6.06%)  7/137 (5.11%) 
Ligament sprain  1  3/36 (8.33%)  1/35 (2.86%)  1/66 (1.52%)  5/137 (3.65%) 
Investigations         
11-deoxycortisol increased  1  3/36 (8.33%)  1/35 (2.86%)  2/66 (3.03%)  6/137 (4.38%) 
Activated partial thromboplastin time prolonged  1  3/36 (8.33%)  1/35 (2.86%)  1/66 (1.52%)  5/137 (3.65%) 
Alanine aminotransferase increased  1  0/36 (0.00%)  0/35 (0.00%)  4/66 (6.06%)  4/137 (2.92%) 
Aspartate aminotransferase increased  1  0/36 (0.00%)  0/35 (0.00%)  4/66 (6.06%)  4/137 (2.92%) 
Blood cholesterol increased  1  2/36 (5.56%)  0/35 (0.00%)  1/66 (1.52%)  3/137 (2.19%) 
Blood corticotrophin increased  1  8/36 (22.22%)  6/35 (17.14%)  14/66 (21.21%)  28/137 (20.44%) 
Blood testosterone increased  1  2/36 (5.56%)  1/35 (2.86%)  13/66 (19.70%)  16/137 (11.68%) 
Cortisol decreased  1  3/36 (8.33%)  0/35 (0.00%)  1/66 (1.52%)  4/137 (2.92%) 
Cortisol free urine decreased  1  8/36 (22.22%)  2/35 (5.71%)  1/66 (1.52%)  11/137 (8.03%) 
Cortisol free urine increased  1  6/36 (16.67%)  1/35 (2.86%)  1/66 (1.52%)  8/137 (5.84%) 
Haemoglobin decreased  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Hormone level abnormal  1  5/36 (13.89%)  1/35 (2.86%)  12/66 (18.18%)  18/137 (13.14%) 
Lipase increased  1  1/36 (2.78%)  2/35 (5.71%)  1/66 (1.52%)  4/137 (2.92%) 
Low density lipoprotein increased  1  2/36 (5.56%)  0/35 (0.00%)  1/66 (1.52%)  3/137 (2.19%) 
Renin increased  1  3/36 (8.33%)  0/35 (0.00%)  3/66 (4.55%)  6/137 (4.38%) 
Weight decreased  1  2/36 (5.56%)  2/35 (5.71%)  5/66 (7.58%)  9/137 (6.57%) 
Weight increased  1  1/36 (2.78%)  2/35 (5.71%)  2/66 (3.03%)  5/137 (3.65%) 
Metabolism and nutrition disorders         
Decreased appetite  1  3/36 (8.33%)  7/35 (20.00%)  11/66 (16.67%)  21/137 (15.33%) 
Hypercholesterolaemia  1  1/36 (2.78%)  2/35 (5.71%)  1/66 (1.52%)  4/137 (2.92%) 
Hyperglycaemia  1  2/36 (5.56%)  0/35 (0.00%)  1/66 (1.52%)  3/137 (2.19%) 
Hypertriglyceridaemia  1  2/36 (5.56%)  0/35 (0.00%)  2/66 (3.03%)  4/137 (2.92%) 
Hypokalaemia  1  3/36 (8.33%)  3/35 (8.57%)  11/66 (16.67%)  17/137 (12.41%) 
Iron deficiency  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Vitamin D deficiency  1  3/36 (8.33%)  1/35 (2.86%)  2/66 (3.03%)  6/137 (4.38%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  7/36 (19.44%)  10/35 (28.57%)  12/66 (18.18%)  29/137 (21.17%) 
Back pain  1  9/36 (25.00%)  13/35 (37.14%)  7/66 (10.61%)  29/137 (21.17%) 
Limb discomfort  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Muscle spasms  1  0/36 (0.00%)  2/35 (5.71%)  6/66 (9.09%)  8/137 (5.84%) 
Musculoskeletal pain  1  2/36 (5.56%)  1/35 (2.86%)  3/66 (4.55%)  6/137 (4.38%) 
Myalgia  1  2/36 (5.56%)  7/35 (20.00%)  11/66 (16.67%)  20/137 (14.60%) 
Neck pain  1  2/36 (5.56%)  2/35 (5.71%)  3/66 (4.55%)  7/137 (5.11%) 
Osteoarthritis  1  3/36 (8.33%)  0/35 (0.00%)  1/66 (1.52%)  4/137 (2.92%) 
Osteopenia  1  2/36 (5.56%)  2/35 (5.71%)  1/66 (1.52%)  5/137 (3.65%) 
Osteoporosis  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Pain in extremity  1  2/36 (5.56%)  5/35 (14.29%)  6/66 (9.09%)  13/137 (9.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Pituitary tumour benign  1  2/36 (5.56%)  1/35 (2.86%)  6/66 (9.09%)  9/137 (6.57%) 
Nervous system disorders         
Amnesia  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Carpal tunnel syndrome  1  2/36 (5.56%)  1/35 (2.86%)  0/66 (0.00%)  3/137 (2.19%) 
Dizziness  1  5/36 (13.89%)  4/35 (11.43%)  17/66 (25.76%)  26/137 (18.98%) 
Headache  1  11/36 (30.56%)  7/35 (20.00%)  32/66 (48.48%)  50/137 (36.50%) 
Hypoaesthesia  1  1/36 (2.78%)  4/35 (11.43%)  4/66 (6.06%)  9/137 (6.57%) 
Memory impairment  1  2/36 (5.56%)  1/35 (2.86%)  2/66 (3.03%)  5/137 (3.65%) 
Migraine  1  0/36 (0.00%)  1/35 (2.86%)  4/66 (6.06%)  5/137 (3.65%) 
Paraesthesia  1  1/36 (2.78%)  4/35 (11.43%)  0/66 (0.00%)  5/137 (3.65%) 
Somnolence  1  2/36 (5.56%)  0/35 (0.00%)  3/66 (4.55%)  5/137 (3.65%) 
Psychiatric disorders         
Anxiety  1  3/36 (8.33%)  2/35 (5.71%)  7/66 (10.61%)  12/137 (8.76%) 
Depression  1  3/36 (8.33%)  3/35 (8.57%)  7/66 (10.61%)  13/137 (9.49%) 
Insomnia  1  4/36 (11.11%)  2/35 (5.71%)  7/66 (10.61%)  13/137 (9.49%) 
Irritability  1  1/36 (2.78%)  1/35 (2.86%)  4/66 (6.06%)  6/137 (4.38%) 
Panic attack  1  0/36 (0.00%)  2/35 (5.71%)  0/66 (0.00%)  2/137 (1.46%) 
Sleep disorder  1  2/36 (5.56%)  0/35 (0.00%)  5/66 (7.58%)  7/137 (5.11%) 
Renal and urinary disorders         
Nephrolithiasis  1  1/36 (2.78%)  2/35 (5.71%)  0/66 (0.00%)  3/137 (2.19%) 
Reproductive system and breast disorders         
Menstruation irregular  1  0/36 (0.00%)  2/35 (5.71%)  2/66 (3.03%)  4/137 (2.92%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  5/36 (13.89%)  4/35 (11.43%)  10/66 (15.15%)  19/137 (13.87%) 
Dyspnoea  1  1/36 (2.78%)  1/35 (2.86%)  4/66 (6.06%)  6/137 (4.38%) 
Nasal congestion  1  3/36 (8.33%)  0/35 (0.00%)  3/66 (4.55%)  6/137 (4.38%) 
Oropharyngeal pain  1  3/36 (8.33%)  4/35 (11.43%)  7/66 (10.61%)  14/137 (10.22%) 
Rhinitis allergic  1  0/36 (0.00%)  0/35 (0.00%)  4/66 (6.06%)  4/137 (2.92%) 
Rhinorrhoea  1  2/36 (5.56%)  1/35 (2.86%)  4/66 (6.06%)  7/137 (5.11%) 
Skin and subcutaneous tissue disorders         
Acne  1  2/36 (5.56%)  2/35 (5.71%)  9/66 (13.64%)  13/137 (9.49%) 
Alopecia  1  0/36 (0.00%)  3/35 (8.57%)  7/66 (10.61%)  10/137 (7.30%) 
Dermatitis  1  0/36 (0.00%)  2/35 (5.71%)  2/66 (3.03%)  4/137 (2.92%) 
Dermatitis contact  1  2/36 (5.56%)  1/35 (2.86%)  2/66 (3.03%)  5/137 (3.65%) 
Dry skin  1  0/36 (0.00%)  3/35 (8.57%)  7/66 (10.61%)  10/137 (7.30%) 
Eczema  1  1/36 (2.78%)  2/35 (5.71%)  2/66 (3.03%)  5/137 (3.65%) 
Hirsutism  1  4/36 (11.11%)  3/35 (8.57%)  5/66 (7.58%)  12/137 (8.76%) 
Hyperhidrosis  1  3/36 (8.33%)  3/35 (8.57%)  3/66 (4.55%)  9/137 (6.57%) 
Onychoclasis  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
Pruritus  1  5/36 (13.89%)  1/35 (2.86%)  7/66 (10.61%)  13/137 (9.49%) 
Rash  1  8/36 (22.22%)  3/35 (8.57%)  10/66 (15.15%)  21/137 (15.33%) 
Skin hyperpigmentation  1  1/36 (2.78%)  1/35 (2.86%)  4/66 (6.06%)  6/137 (4.38%) 
Skin lesion  1  3/36 (8.33%)  0/35 (0.00%)  1/66 (1.52%)  4/137 (2.92%) 
Urticaria  1  2/36 (5.56%)  0/35 (0.00%)  2/66 (3.03%)  4/137 (2.92%) 
Vascular disorders         
Hypertension  1  5/36 (13.89%)  5/35 (14.29%)  14/66 (21.21%)  24/137 (17.52%) 
Hypotension  1  7/36 (19.44%)  3/35 (8.57%)  3/66 (4.55%)  13/137 (9.49%) 
Varicose vein  1  2/36 (5.56%)  0/35 (0.00%)  0/66 (0.00%)  2/137 (1.46%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
The first 12 weeks of the study consisted of an individual dose-titration period.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e. data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02180217    
Other Study ID Numbers: CLCI699C2301
2013-004766-34 ( EudraCT Number )
First Submitted: June 17, 2014
First Posted: July 2, 2014
Results First Submitted: April 3, 2020
Results First Posted: June 16, 2020
Last Update Posted: January 6, 2021