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osilodrostat

Phase 3

Cushing's Disease | Small molecule | Endocrine |Novartis AG|Last Updated: Nov 1, 2021

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment73

FDA Designations

No designations recorded

Clinical trial landscape

osilodrostat · 5 trials · 10 indications

Phase 3 2Phase 2 1Phase 1 2
NCT02697734Efficacy and Safety Evaluation of Osilodrostat in Cushing's DiseaseCushing's Disease
COMPLETED73 Analytics
NCT02180217Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's DiseaseCushings Disease
COMPLETED137 Analytics
PHASE3COMPLETED
Efficacy and Safety Evaluation of Osilodrostat in Cushing's Disease
Cushing's DiseaseUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease
Cushings DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Randomized Participants With a Complete Response
at Week 12

A complete responder at week 12 is defined as a participant who had a mean urine free cortisol ≤ upper limit of normal (mUFC ≤ ULN) at Week 12. Participants who had a missing mUFC assessment at Week 12 were counted as non-responders for the primary endpoint.

Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata
Week 34 (8 weeks)

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

Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12
Baseline, 12 weeks

Percent change from baseline in the mUFC at the individual patient level

Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: AUClast
Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose

To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function.

Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: AUCinf
Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose

To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function.

Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: Cmax
Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose

To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function.

Pharmacokinetics (PK in urine) of a single dose of 30 mg osilodrostat: CL/F
Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose

To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function.

Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

PK of a single dose of 30 mg osilodrostat: AUCinf
Predose (Day 0) , and at imepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

PK of a single dose of 30 mg osilodrostat: Cmax
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

PK of a single dose of 30 mg osilodrostat: T1/2
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

PK of a single dose of 30 mg osilodrostat: CL/F
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

PK of a single dose of 30 mg osilodrostat: Vz/F
Predose (Day 0) , and timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.

To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

Secondary Endpoints

Percentage of Participants With mUFC ≤ ULN at Week 36
At Week 36
Change From Baseline in mUFC
Baseline, weeks 2,5,8,12,14,17,20,23,26,29,32,36,40,48,60,72,84,96
Time-to-first Control of mUFC - Number (%) of Participants With mUFC <=ULN
up to 12 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
osilodrostat GroupEXPERIMENTALParticipants in this arm were randomized to receive the study drug, osilodrostat followed after Week 12 by open-label osilodrostat at the starting dose (with a second dose titration)
osilodrostat Placebo GroupPLACEBO_COMPARATORParticipants in this arm were randomized to receive osilodrostat placebo followed after Week 12 by open-label osilodrostat at the starting dose (with a dose titration)
osilodrostat (LCI699)EXPERIMENTALConsisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.
LCI699 PlaceboPLACEBO_COMPARATORConsisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.
OsilodrostatEXPERIMENTALPatients in this arm took the study drug, osilodrostat.
osilodrostat ( LCI699)EXPERIMENTALEach participant will undergo a 28 day screening /baseline period (day-28 to Day -1), followed by a 4 day treatment period ( a single 30 mg dose of LCI699 (Day 1) with 4 days of PK smple collection

Interventions

NameTypeDescription
osilodrostatDRUGIn the form of filmcoated tablets for oral administration, in the following dose strengths: 1 mg, 5 mg, 10 mg, and 20 mg.
osilodrostat PlaceboDRUGMatching Placebo in the form of filmcoated tablets for oral administration
LCI699 matching placeboDRUGOsilodrostat 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.
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Eligibility Criteria

Age Range18 Years to 75 Years
SexALL
Healthy VolunteersNo
Study Sites36

Key inclusion criteria: * Confirmed Cushing's Disease (CD) that is persistent or recurrent as evidenced by all of the following criteria being met (i.e., a, b and c): 1. mUFC \> 1.3 x ULN (Mean of three 24-hour urine samples collected preferably on 3 consecutive days, during screening after wash...

Countries:United StatesBelgiumBrazilCanadaChinaCosta RicaGreecePolandPortugalRussiaSpainSwitzerlandThailandTurkey (Türkiye)ArgentinaAustriaBulgariaColombiaFranceGermanyIndiaItalyJapanNetherlandsSouth KoreaUnited Kingdom
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Frequently asked questions about osilodrostat

What is Osilodrostat used for?

Osilodrostat is an investigational small molecule being developed for Cushing's Disease, Cushing's Syndrome, and related conditions such as ectopic corticotropin syndrome, adrenal adenoma, adrenal carcinoma, AIMAH, and PPNAD. It has also been studied in subjects with hepatic or renal impairment.

Who makes Osilodrostat?

Osilodrostat is being developed by Novartis AG, which trades on the New York Stock Exchange under the ticker symbol NVS. The company has conducted clinical trials of the drug across multiple countries including the United States, Japan, and various European nations.

What phase is Osilodrostat in?

Osilodrostat is in Phase 2 clinical development for Cushing's Syndrome, based on a completed Phase 2 trial. It has also completed Phase 1 studies in healthy volunteers with hepatic or renal impairment, and a Phase 3 trial in Cushing's Disease has been completed.

What clinical trials is Osilodrostat in?

Osilodrostat has completed four clinical trials: NCT02372084 (Phase 1, hepatic impairment), NCT02399202 (Phase 1, renal impairment), NCT02468193 (Phase 2, Cushing's Syndrome), and NCT02697734 (Phase 3, Cushing's Disease). All trials are completed with no active trials currently listed.

Is Osilodrostat FDA approved?

Osilodrostat is an investigational drug and is not FDA approved. It remains in clinical development, with completed trials including a Phase 3 study in Cushing's Disease. No approval status has been reported for this drug.

How does Osilodrostat work?

Osilodrostat works by inhibiting cortisol synthesis, though the specific molecular target has not been disclosed. It is being studied to reduce cortisol levels in conditions like Cushing's Disease and Cushing's Syndrome, where excess cortisol causes symptoms.