A Phase 3 interventional study of osilodrostat and LCI699 matching placebo in Cushings Disease, sponsored by Novartis Pharmaceuticals. Completed at 60 sites in 19 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-01-06.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
The study aimed to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It was a pivotal trial which supported the registration of LCI699 for the treatment of patients with Cushing's disease in the US and the EU.
This is a phase lll, multi-center, double-blind, randomized withdrawal study of LCI699 following a 24 week, single-arm, open-label dose titration and treatment period which evaluated the safety and efficacy of LCI699 for the treatment of patients with Cushing's disease.
The primary objective compared the complete response rate at the end of the 8-week period of randomized withdrawal (Week 34) between patients randomized to continued osilodrostat therapy vs.
placebo. The key secondary objective assessed the complete response rate at the end of individual dose titration and treatment with osilodrostat in the initial single-arm, open label period (Week 24).
Eligible patients were randomized in a double-blinded fashion at Week 26 at a 1:1 ratio either to continue treatment with osilodrostat at the same dose or to matching placebo. Randomization was stratified by osilodrostat dose at Week 24 (≤ 5mg bid vs. >5mg bid); and history of pituitary irradiation (yes/no).
The study had four periods combined in the Core Period (Study Period 1 to 4) and an optional Extension Period. The optional Extension Period starting at Week 48.
Study Period 1 consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients (Week 1 to Week 12). Dose adjustments were based on the mean of three 24-hour UFC (mUFC) values as measured by the central laboratory.
During study Period 2 (Week 13 to Week 24), osilodrostat efficacy and safety were assessed at the therapeutic dose determined during study Period 1. Patients whose mUFC became elevated during this period had their osilodrostat dose increased further, if it was tolerated, up to 30 mg bid. Such patients were followed for long-term safety and efficacy and were not considered responders for the key secondary endpoint, hence were not randomized in Study Period 3.
Study Period 3 was a double-blind, placebo-controlled randomized withdrawal (RW) Period (Week 26 to Week 34). In order to be eligible for randomization in study Period 3, patients had to have completed dose titration during study Period 1, and had to be classified as complete responders at Week 24 of study Period 2. Patients not eligible for randomization received open-label osilodrostat until the end of the Core Period (Week 48), unless there was a reason to discontinue from the study prematurely.
During study Period 3, mUFC was measured at scheduled visits every 2 weeks. However, patients were also allowed to have unscheduled visits at any time during the RW if they reported symptoms of hypercortisolism or hypocortisolism.
The dose of study drug remained unchanged for patients who maintained a normal mUFC and did not develop adverse events (AEs) related to study drug during RW. The Investigator could reduce or temporally withhold a dose of study drug for safety reasons at any time during the study, including the RW Period.
During this study period, a patient was discontinued from the RW Period and declared a nonresponder, if the mUFC increased to >1.5×ULN. After discontinuation from RW treatment, or at the end of the RW Period (Week 34), whichever came first, the patient resumed open-label osilodrostat at a dose selected by the Investigator.
Patients who discontinued from the study during the RW Period were no longer in the study, and consequently were not permitted to receive open-label osilodrostat and could not move to study Period 4.
Patients who discontinued from RW treatment due to lack of efficacy resumed open-label osilodrostat at the time of discontinuation, which could occur before Week 34. Patients who were not discontinued during RW resumed open-label osilodrostat at the end of RW (Week 34) and continued osilodrostat thereafter (study Period 4).
The Novartis study team, the patient, the Investigator, and all other site staff remained blinded to treatment assignment from the time of randomization to the time of database lock at the end of the Core Period. Novartis Drug Supply Management department members were unblinded in order to prepare the study drug supplies.
Study Period 4 was a single-arm, open-label therapy (end of Week 34 to Week 48). At the end of Week 34, all patients received open-label osilodrostat treatment. The Investigator had the discretion to select the dose during this period.
Patients continued open-label therapy until Week 48. At Week 48, patients had the option to enter an Extension Period, or discontinue osilodrostat at Week 48 to conclude with an end of Core Period visit 4 weeks off study drug (at Week 52).
Patients who continued to receive clinical benefit, as assessed by the study Investigator, and who wished to enter the Extension Period were re-consented at Week 48. Patients entered the Extension period without interruption of study drug or assessments. At the end of the study, patients who continued to benefit from treatment were offered to participate in a separate long-term safety follow-up study. The optional Extension Period ended after all patients completed Week 72 or discontinued early.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
Drug: osilodrostat
Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
Drug: LCI699 matching placebo
Osilodrostat comes in the form of film-coated tablets for oral administration, in the following strengths: 1 mg, 5 mg, 10 mg, and 20 mg. The maximum dose of osilodrostat was 30 mg bid.
Also known as: LCI699
Osilodrostat placebo comes in the form of film-coated tablets for oral administration, in the following strengths: 1 mg, 5 mg, 10 mg, and 20 mg. The maximum dose of osilodrostat placebo was 30 mg bid.
Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata
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)
Percentage of Secondary Efficacy Responder at Week 24 (Key Secondary Endpoint)
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
Time-to-loss of Control of Mean Urinary Free Cortisol (mUFC) by Randomized Treatment Group
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
Complete Response Rate (CRR)
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
Actual Change From Baseline in mUFC
Actual change in mUFC from baseline.
Time frame: Weeks 12, 24, 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Fasting Glucose
Actual change in fasting glucose from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Hemoglobin A1C (HbA1C)
Actual change in glycosylated hemoglobin (HbA1c) from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride
Actual change in Cholesterol, LDL Cholesterol, HDL Cholesterol \& Triglyceride from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Sitting Systolic Blood Pressure (SBP) & Sitting Diastolic Blood Pressure (DBP)
Actual change in sitting SBP \& DBP from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Weight
Actual change in weight from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Body Mass Index (BMI)
Actual change in BMI from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Waist Circumference
Actual change in waist circumference from baseline.
Time frame: Baseline, Weeks 48, 72, last available assessment
Actual Change From Baseline in Patient-Reported Outcomes (Cushing's Health-Related Quality of Life (QoL)) - Total Score
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
Actual Change From Baseline in Patient-Reported Outcomes: Beck Depression Inventory-II (BDI-II)
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
Actual Change in Patient-Reported Outcomes: EQ-5D-5L Utility Index
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
Actual Change in Patient-Reported Outcomes: EQ-5D-5L Vascular Analog Scale (VAS)
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
Change From Baseline in the Physical Features of Cushing's Disease by Photography
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
Change From Baseline in Bone Mineral Density - All Participants
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)
Time-to-escape
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
LCI699 Exposures
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
Percentage of Participants With Complete Response Rate (CRR)
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
Percentage of Participants With Partial Response Rate (PRR)
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
Percentage of Participants With Overall Response Rate (ORR)
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
132 patients were planned, 137 were enrolled and 137 were analyzed.
| Milestone | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| 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 | 24 | 27 | 28 |
| Not completed | 12 | 8 | 38 |
| Withdrew: Adverse event | 3 | 2 | 22 |
| Withdrew: Death | 1 | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 | 4 |
| Withdrew: Subject/guardian decision | 5 | 3 | 6 |
| Withdrew: Physician decision | 1 | 1 | 6 |
| Withdrew: Unsatisfactory therapeutic effect | 1 | 0 | 0 |
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
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo |
|---|---|---|
| Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata | 86.1 | 29.4 |
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.
| Percentage of participants | All Participants |
|---|---|
| Percentage of Secondary Efficacy Responder at Week 24 (Key Secondary Endpoint) | 52.6 (43.9 to 61.1) |
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.
| Percentage | Osilodrostat (LCI699) | LCI699 Placebo |
|---|---|---|
| Time-to-loss of Control of Mean Urinary Free Cortisol (mUFC) by Randomized Treatment Group | 5.6 (1.4 to 20.4) | 61.1 (45.0 to 77.5) |
Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Week 12 | 86.1 | 91.4 | 53.0 |
| Week 24 | 100.0 | 97.1 | 34.8 |
| Week 48 | 88.9 | 77.1 | 48.5 |
| Week 72 | 82.9 | 83.3 | 78.0 |
| Last observed value | 69.4 | 74.3 | 53.0 |
Actual change in mUFC from baseline.
| nmol/24h | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Actual Baseline (BL) | 890.0 ± 1275.66 | 560.0 ± 548.84 | 1305.8 ± 2012.21 |
| Wk 12: Act. change from BL | -848.4 ± 1335.66 | -510.3 ± 556.84 | -1021.3 ± 1825.55 |
| Wk 24: Act. change from BL | -821.2 ± 1283.03 | -485.5 ± 558.99 | -930.3 ± 1778.04 |
| Wk 48: Act. change from BL | -708.2 ± 983.14 | -477.1 ± 529.04 | -1189.9 ± 2042.48 |
| Wk 72: Act. change from BL | -680.7 ± 1003.63 | -536.7 ± 585.78 | -826.7 ± 1684.92 |
| Last avail. assess.: Act. change from BL | -795.2 ± 1286.22 | -387.3 ± 605.63 | -893.4 ± 1969.56 |
Actual change in fasting glucose from baseline.
| mg/dL | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 102.7 ± 35.23 | 90.5 ± 18.53 | 101.8 ± 31.00 |
| Wk 48 | -7.9 ± 32.24 | -5.5 ± 12.13 | -14.1 ± 22.66 |
| Wk 72 | -0.5 ± 16.84 | -4.4 ± 15.13 | -10.8 ± 24.02 |
| Last avail. assessment | -8.6 ± 37.05 | -0.6 ± 21.00 | -15.6 ± 26.62 |
Actual change in glycosylated hemoglobin (HbA1c) from baseline.
| percentage | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 6.1 ± 0.98 | 5.8 ± 0.93 | 6.0 ± 0.97 |
| Wk 48 | -0.3 ± 0.86 | -0.4 ± 0.56 | -0.4 ± 0.65 |
| Wk 72 | -0.4 ± 0.66 | -0.4 ± 0.47 | -0.4 ± 0.64 |
| Last avail. assessment | -0.3 ± 0.78 | -0.2 ± 0.47 | -0.3 ± 0.68 |
Actual change in Cholesterol, LDL Cholesterol, HDL Cholesterol \& Triglyceride from baseline.
| mmol/L | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Cholesterol: BL | 5.5 ± 1.22 | 5.3 ± 0.90 | 5.1 ± 1.24 |
| Cholesterol: Wk 48 | -0.7 ± 0.87 | -0.4 ± 0.89 | -0.5 ± 0.90 |
| Cholesterol: Wk 72 | -0.4 ± 0.96 | -0.3 ± 0.75 | -0.4 ± 0.98 |
| Cholesterol: Last avail. assessment | -0.3 ± 1.16 | -0.3 ± 1.03 | -0.4 ± 1.15 |
| LDL Cholesterol: BL | 3.2 ± 1.09 | 3.1 ± 0.77 | 2.9 ± 0.94 |
| LDL Cholesterol: Wk 48 | -0.3 ± 0.75 | -0.2 ± 0.74 | -0.1 ± 0.82 |
| LDL Cholesterol: Wk 72 | -0.2 ± 0.77 | -0.2 ± 0.66 | -0.1 ± 0.86 |
| LDL Cholesterol: Last avail asses | -0.1 ± 0.98 | -0.2 ± 0.88 | -0.1 ± 0.99 |
| HDL Cholesterol: BL | 1.7 ± 0.55 | 1.5 ± 0.36 | 1.6 ± 0.42 |
| HDL Cholesterol: Wk 48 | -0.3 ± 0.39 | -0.2 ± 0.17 | -0.3 ± 0.28 |
| HDL Cholesterol: Wk 72 | -0.2 ± 0.39 | -0.2 ± 0.27 | -0.3 ± 0.28 |
| HDL Cholesterol: Last avail assess | -0.2 ± 0.40 | -0.1 ± 0.27 | -0.2 ± 0.34 |
| Triglyceride: BL | 1.5 ± 0.78 | 1.4 ± 0.62 | 1.6 ± 1.74 |
| Triglyceride: Wk 48 | -0.1 ± 0.49 | 0.0 ± 0.54 | 0.0 ± 1.22 |
| Triglyceride: Wk 72 | 0.0 ± 0.57 | -0.1 ± 0.67 | 0.0 ± 0.60 |
| Triglyceride: Last avail. assess | 0.0 ± 0.64 | -0.1 ± 0.75 | 0.1 ± 1.48 |
Actual change in sitting SBP \& DBP from baseline.
| mmHg | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| SBP: Baseline | 132.2 ± 15.44 | 128.8 ± 11.93 | 134.0 ± 16.34 |
| SBP: Wk 48 | -15.2 ± 17.00 | -4.8 ± 12.28 | -9.2 ± 15.48 |
| SBP: Wk 72 | -12.2 ± 15.90 | -8.2 ± 19.41 | -9.4 ± 19.08 |
| SBP: Last avail. assessment | -8.2 ± 15.25 | -4.6 ± 15.20 | -10.8 ± 15.31 |
| DBP: Baseline | 85.3 ± 11.38 | 85.0 ± 10.03 | 85.4 ± 10.53 |
| DBP: Wk 48 | -7.8 ± 11.63 | -5.1 ± 9.66 | -6.0 ± 11.79 |
| DBP: Wk 72 | -5.9 ± 11.17 | -7.0 ± 10.33 | -4.8 ± 12.26 |
| DBP: Last avail. assessment | -3.4 ± 11.79 | -3.5 ± 11.50 | -5.0 ± 10.45 |
Actual change in weight from baseline.
| kg | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 78.2 ± 19.02 | 83.4 ± 24.73 | 80.7 ± 23.06 |
| Wk 48 | -3.4 ± 5.64 | -3.9 ± 5.77 | -4.0 ± 5.82 |
| Wk 72 | -3.7 ± 6.93 | -5.0 ± 6.03 | -5.6 ± 6.75 |
| Last avail. assessment | -2.9 ± 8.28 | -3.7 ± 11.13 | -4.2 ± 6.35 |
Actual change in BMI from baseline.
| kg/m^2 | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 29.6 ± 7.36 | 30.9 ± 8.38 | 30.4 ± 7.74 |
| Wk 48 | -1.3 ± 2.22 | -1.5 ± 2.12 | -1.5 ± 2.17 |
| Wk 72 | -1.4 ± 2.79 | -1.8 ± 2.14 | -2.0 ± 2.55 |
| Last avail. assessment | -1.2 ± 3.34 | -1.5 ± 3.94 | -1.6 ± 2.41 |
Actual change in waist circumference from baseline.
| cm | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 100.5 ± 16.81 | 103.7 ± 18.26 | 105.0 ± 21.15 |
| Wk 48 | -5.1 ± 6.26 | -4.2 ± 10.12 | -4.7 ± 7.07 |
| Wk 72 | -5.1 ± 7.18 | -6.1 ± 9.86 | -7.4 ± 8.53 |
| Last avail. assessment | -4.7 ± 10.05 | -5.2 ± 12.24 | -6.2 ± 9.96 |
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.
| scores on a scale | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 44.4 ± 18.33 | 43.2 ± 22.45 | 40.5 ± 17.61 |
| Week 48 | 16.1 ± 15.15 | 10.2 ± 16.57 | 13.2 ± 17.79 |
| Week 72 | 15.8 ± 16.08 | 12.6 ± 20.68 | 16.3 ± 21.31 |
| Last available assess. | 16.1 ± 15.99 | 11.8 ± 20.51 | 12.9 ± 18.91 |
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.
| scores on a a scale | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 15.1 ± 11.14 | 17.8 ± 9.93 | 17.3 ± 10.67 |
| W48 | -4.8 ± 9.84 | -5.3 ± 7.99 | -7.0 ± 10.17 |
| W72 | -6.0 ± 9.55 | -4.6 ± 9.41 | -9.0 ± 12.34 |
| Last avail. assess. | -6.2 ± 9.93 | -5.0 ± 9.49 | -4.9 ± 10.66 |
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.
| Scores on a scale | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 0.7 ± 0.24 | 0.7 ± 0.24 | 0.7 ± 0.28 |
| Week 48 | 0.1 ± 0.18 | 0 ± 0.25 | 0.1 ± 0.18 |
| Week 72 | 0.1 ± 0.18 | 0.1 ± 0.26 | 0.1 ± 0.19 |
| Last avail. assess. | 0.1 ± 0.22 | 0 ± 0.28 | 0.1 ± 0.23 |
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.
| Scores on a scale | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline | 61.3 ± 18.97 | 64.2 ± 16.37 | 60.8 ± 21.09 |
| Week 48 | 12.6 ± 20.64 | 6.9 ± 12.56 | 9.7 ± 17.16 |
| Week 72 | 11.2 ± 18.98 | 6.6 ± 15.47 | 10.1 ± 19.80 |
| Last avail. assess. | 12.1 ± 19.71 | 6.4 ± 18.65 | 6.2 ± 20.42 |
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).
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| W48: Facial rubor | 50.0 (31.3 to 68.7) | 46.7 (28.3 to 65.7) | 43.2 (27.1 to 60.5) |
| W48: Striae | 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 | 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 | 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 | 40.0 (22.7 to 59.4) | 26.7 (12.3 to 45.9) | 45.9 (29.5 to 63.1) |
| W48: Central obesity | 43.3 (25.5 to 62.6) | 30.0 (14.7 to 49.4) | 51.4 (34.4 to 68.1) |
| W48: Ecchymoses | 33.3 (17.3 to 52.8) | 26.7 (12.3 to 45.9) | 43.2 (27.1 to 60.5) |
| W72: Facial rubor | 48.3 (29.4 to 67.5) | 55.6 (35.3 to 74.5) | 53.3 (34.3 to 71.7) |
| W72: Striae | 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 | 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 | 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 | 31.0 (15.3 to 50.8) | 25.9 (11.1 to 46.3) | 46.7 (28.3 to 65.7) |
| W72: Central obesity | 37.9 (20.7 to 57.7) | 37.0 (19.4 to 57.6) | 43.3 (25.5 to 62.6) |
| W72: Ecchymoses | 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 | 60.0 (38.7 to 78.9) | 56.5 (34.5 to 76.8) | 53.8 (33.4 to 73.4) |
| EOT: Striae | 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 | 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 | 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 | 36.0 (18.0 to 57.5) | 21.7 (7.5 to 43.7) | 50.0 (29.9 to 70.1) |
| EOT: Central obesity | 40.0 (21.1 to 61.3) | 39.1 (19.7 to 61.5) | 38.5 (20.0 to 59.4) |
| EOT: Ecchymoses | 28.0 (12.1 to 49.4) | 39.1 (19.7 to 61.5) | 38.5 (20.2 to 59.4) |
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..
| g/cm2 | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Baseline (L1-L4 Lumbar Spine) | 1.0 ± 0.20 | 1.0 ± 0.17 | 1.0 ± 0.18 |
| W48 (L1-L4 Lumbar Spine) | 1.0 ± 0.19 | 1.0 ± 0.17 | 1.0 ± 0.19 |
| LOV (L1-L4 Lumbar Spine) | 1.0 ± 0.20 | 1.0 ± 0.18 | 1.0 ± 0.18 |
| Baseline (Total Hip) | 0.9 ± 0.18 | 0.8 ± 0.15 | 0.9 ± 0.16 |
| W48 (Total Hip) | 0.9 ± 0.17 | 0.8 ± 0.14 | 0.9 ± 0.16 |
| LOV (Total Hip) | 0.9 ± 0.17 | 0.8 ± 0.13 | 0.9 ± 0.16 |
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.
| days | All Participants |
|---|---|
| Time-to-escape | 546.0 (212.0 to 968.0) |
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.
| ng/ml | Osilodrostat (LCI699) 2 mg | Osilodrostat (LCI699) 3 mg | Osilodrostat (LCI699) 5 mg | Osilodrostat (LCI699) 7 mg |
|---|---|---|---|---|
| Week (Wk) 2: Predose | 1.904 ± 110.4 | — | — | — |
| Wk 2: 0.75h | 1.907 ± 132.5 | — | — | — |
| Wk 2: 1.5h | 5.1 ± 62.7 | — | — | — |
| Wk 2: 4h | 5.818 ± 66.3 | — | — | — |
| Wk 4: Predose | 2.104 ± 108.0 | 2.898 ± 109.1 | 3.584 ± 126.3 | — |
| Wk 4: 0.75h | 0.859 ± 254.3 | — | 7.091 ± 137.8 | — |
| Wk 4: 1.5h | 8.737 ± 3.6 | — | 24.2 ± NA | — |
| Wk 4: 4h | 8.930 ± NA | — | 15.985 ± 48.3 | — |
| Wk 6: Predose | 2.037 ± 63.5 | 2.392 ± 285.6 | 5.087 ± 122.9 | 8.065 ± 8.6 |
| Wk 6: 0.75h | 3.110 ± NA | — | 5.223 ± 229.4 | — |
| Wk 6: 1.5h | — | 22.4 ± NA | 21.4 ± NA | — |
| Wk 6: 4h | 8.380 ± NA | 18.6 ± NA | 18.373 ± 36.5 | — |
| Wk 8: Predose | 2.198 ± 108.9 | 4.061 ± 67.4 | 4.487 ± 106.9 | 6.718 ± 34.2 |
| Wk 8: 1.5h | 10.8 ± NA | 20.4 ± NA | — | 32.1 ± NA |
| Wk 8: 4h | 6.65 ± NA | — | — | 32 ± NA |
| Wk 10: Predose | 1.862 ± 128.9 | 3.007 ± 64.8 | 4.704 ± 106.8 | 5.451 ± 93.1 |
| Wk 10: 0.75h | — | 6.7 ± NA | — | 17.1 ± NA |
| Wk 10: 1.5h | 12.1 ± NA | 18.3 ± NA | 34.2 ± NA | — |
| Wk 10: 4h | — | 15.8 ± NA | 27.2 ± NA | 35.5 ± NA |
Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN.
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Week 12 | 6.1 | 91.4 | 53.0 |
| Week 24 | 100 | 97.1 | 34.8 |
| Week 48 | 88.9 | 77.1 | 48.5 |
| Week 72 | 82.9 | 83.3 | 78.0 |
| Last available assess. | 69.4 | 74.3 | 53.0 |
Partial response rate is defined as percentage of enrolled participants with ≥ 50% reduction from baseline in mUFC, but mUFC\>ULN)
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Week 12 | 2.8 | 5.7 | 24.2 |
| Week 24 | 0.0 | 0.0 | 30.3 |
| Week 48 | 5.6 | 11.4 | 10.6 |
| Week 72 | 8.6 | 13.3 | 2.4 |
| Last available assess. | 22.2 | 11.4 | 22.7 |
Overall response rate is defined as percentage of enrolled participants with mUFC ≤ ULN or at least 50% reduction from baseline.
| Percentage of participants | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized |
|---|---|---|---|
| Week 12 | 88.9 | 97.1 | 77.3 |
| Week 24 | 100 | 97.1 | 65.2 |
| Week 48 | 94.4 | 88.6 | 59.1 |
| Week 72 | 91.4 | 96.7 | 80.5 |
| Last available assess. | 91.7 | 85.7 | 75.8 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Osilodrostat | 1/36 (2.8%) | 13/36 (36.1%) | 34/36 (94.4%) |
| LCI699 Placebo | 1/35 (2.9%) | 10/35 (28.6%) | 35/35 (100%) |
| Non-randomized | 0/66 (0%) | 32/66 (48.5%) | 65/66 (98.5%) |
| All Participants | 2/137 (1.5%) | 55/137 (40.1%) | 134/137 (97.8%) |
| Event | Osilodrostat | LCI699 Placebo | Non-randomized | All Participants |
|---|---|---|---|---|
| Adrenal insufficiencyEndocrine disorders | 1/36 | 1/35 | 6/66 | 8/137 |
| Pituitary tumourNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/36 | 1/35 | 4/66 | 6/137 |
| Adrenocortical insufficiency acuteEndocrine disorders | 1/36 | 0/35 | 3/66 | 4/137 |
| GastroenteritisInfections and infestations | 0/36 | 1/35 | 3/66 | 4/137 |
| VIth nerve paralysisNervous system disorders | 0/36 | 0/35 | 3/66 | 3/137 |
| Glucocorticoid deficiencyEndocrine disorders | 0/36 | 0/35 | 2/66 | 2/137 |
| InfluenzaInfections and infestations | 1/36 | 0/35 | 2/66 | 3/137 |
| Malignant pituitary tumourNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/36 | 0/35 | 2/66 | 2/137 |
| Pituitary tumour benignNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/36 | 0/35 | 2/66 | 3/137 |
| HeadacheNervous system disorders | 0/36 | 1/35 | 2/66 | 3/137 |
| Event | Osilodrostat | LCI699 Placebo | Non-randomized | All Participants |
|---|---|---|---|---|
| NauseaGastrointestinal disorders | 17/36 | 11/35 | 34/66 | 62/137 |
| HeadacheNervous system disorders | 11/36 | 7/35 | 32/66 | 50/137 |
| FatigueGeneral disorders | 8/36 | 13/35 | 24/66 | 45/137 |
| Back painMusculoskeletal and connective tissue disorders | 9/36 | 13/35 | 7/66 | 29/137 |
| VomitingGastrointestinal disorders | 7/36 | 5/35 | 21/66 | 33/137 |
| NasopharyngitisInfections and infestations | 9/36 | 11/35 | 13/66 | 33/137 |
| AstheniaGeneral disorders | 11/36 | 5/35 | 11/66 | 27/137 |
| Adrenal insufficiencyEndocrine disorders | 7/36 | 10/35 | 17/66 | 34/137 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 7/36 | 10/35 | 12/66 | 29/137 |
| Glucocorticoid deficiencyEndocrine disorders | 10/36 | 9/35 | 8/66 | 27/137 |
Full analysis set (FAS): comprises all enrolled patients who received at least one dose of osilodrostat.
| Age, Continuous(years) | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized | Total |
|---|---|---|---|---|
| Mean | 44.3 ± 11.27 | 42.0 ± 13.47 | 39.0 ± 13.38 | 41.2 ± 12.98 |
| Sex: Female, Male(Participants) | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized | Total |
|---|---|---|---|---|
| Female | 30 | 22 | 54 | 106 |
| Male | 6 | 13 | 12 | 31 |
| Race/Ethnicity, Customized(Participants) | Osilodrostat (LCI699) | LCI699 Placebo | Non-randomized | Total |
|---|---|---|---|---|
| Caucasian | 27 | 23 | 39 | 89 |
| Black | 0 | 3 | 1 | 4 |
| Asian | 7 | 7 | 25 | 39 |
| Other | 2 | 2 | 1 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Data sharing details ↗ · www.clinicalstudydatarequest.com
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Studies of the drug tested here: Osilodrostat
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