Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as osilodrastat, osilodrostat
LCI699 · 10 trials · 14 indications
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.
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 from baseline in the mUFC at the individual patient level
A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 10 was ≤ Upper Limit of Normal (ULN), as defined by the local laboratories, or represented a ≥50% decrease from baseline. Patients who discontinued for a disease or treatment related reason (e.g. death, adverse event, clinical disease progression etc.), or whose mean Week 10 24-hour UFC levels were higher than the normal limit and experienced \<50% decrease in UFC were classified as non-responders.
As per the protocol, MTD is the dose at which 4 participants exhibited ACTH-stimulated cortisol results \<400 nanomoles per liter (nmol/L). The change in the distribution across the treatments were analyzed using 1- way analysis of variance (ANOVA) for continuous variables.
Arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and country as factors and Baseline MSSBP as a covariate.
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| osilodrostat Group | EXPERIMENTAL | Participants 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 Group | PLACEBO_COMPARATOR | Participants 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) | EXPERIMENTAL | Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period. |
| LCI699 Placebo | PLACEBO_COMPARATOR | Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period. |
| Osilodrostat | EXPERIMENTAL | Patients in this arm took the study drug, osilodrostat. |
| Part l: Core cohort | EXPERIMENTAL | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part I of this study. 4 patients in this cohort moved to Part II of the study |
| Part II Core: Expansion cohort | EXPERIMENTAL | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Expansion of this study. These patients were all newly enrolled into the phase II part of the study |
| Part II Core: Follow-up cohort | EXPERIMENTAL | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Follow-up of this study. These patients were patients who transferred from Part I Core phase of the study |
| Cohort A: LCI699 0.5 mg QD | EXPERIMENTAL | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. |
| Cohort A: LCI699 1.0 mg QD | EXPERIMENTAL | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Cohort B1: LCI699 1.0 mg BID | EXPERIMENTAL | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. |
| Cohort B1: LCI699 2.0 mg QD | EXPERIMENTAL | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. |
| LCI699 0.25 mg BID | EXPERIMENTAL | Following a 2-week placebo run-in period, participants received LCI699 0.25 mg, capsules, orally, twice daily (BID), with or without food for up to 8 weeks. |
| LCI699 1 mg QD | EXPERIMENTAL | Following a 2-week placebo run-in period, participants received LCI699 1 mg, capsules, orally, once daily (QD), with or without food for up to 8 weeks. |
| LCI699 0.5 mg followed by LCI699 1 mg BID | EXPERIMENTAL | Following a 2-week placebo run-in period, participants received LCI699 0.5 mg, capsules, orally, BID, with or without food for up to 4 weeks, followed by LCI699 1 mg, capsules, orally, BID with or without food for up to 4 weeks. |
| Eplerenone 50 mg BID | ACTIVE_COMPARATOR | Following a 2-week placebo run-in period, participants received eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. |
| Core Period: LCI699 0.25 mg QD | EXPERIMENTAL | Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks. |
| Core Period: LCI699 0.5 mg QD | EXPERIMENTAL | Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks. |
| Core Period: LCI699 1.0 mg QD | EXPERIMENTAL | Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks. |
| Core Period: LCI699 0.5 mg BID | EXPERIMENTAL | Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks. |
| Core Period: Eplerenone 50 mg BID | ACTIVE_COMPARATOR | Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks. |
| Core Period: Placebo | PLACEBO_COMPARATOR | Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks. |
| Withdrawal Period: LCI699 0.25 mg QD | EXPERIMENTAL | Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 0.25 mg QD Placebo | PLACEBO_COMPARATOR | Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 0.5 mg QD | EXPERIMENTAL | Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 0.5 mg QD Placebo | PLACEBO_COMPARATOR | Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 1.0 mg QD | EXPERIMENTAL | Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 1.0 mg QD Placebo | PLACEBO_COMPARATOR | Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 0.5 mg BID | EXPERIMENTAL | Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: LCI699 0.5 mg BID Placebo | PLACEBO_COMPARATOR | Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: Eplerenone 50 mg BID | ACTIVE_COMPARATOR | Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: Eplerenone 50 mg BID Placebo | PLACEBO_COMPARATOR | Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9). |
| Withdrawal Period: Placebo | PLACEBO_COMPARATOR | Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9). |
| LCI696 1mg bid | EXPERIMENTAL | - |
| osilodrostat ( LCI699) | EXPERIMENTAL | Each 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 |
| Name | Type | Description |
|---|---|---|
| osilodrostat | DRUG | In the form of filmcoated tablets for oral administration, in the following dose strengths: 1 mg, 5 mg, 10 mg, and 20 mg. |
| osilodrostat Placebo | DRUG | Matching Placebo in the form of filmcoated tablets for oral administration |
| LCI699 matching placebo | DRUG | 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. |
| LCI699 | DRUG | Osilodrostat 1 mg and 5 mg capsules, was prepared by Novartis and supplied to the Investigator. The capsule formulation of osilodrostat was later changed to tablets and this change was implemented in the study with Protocol amendment 6. Osilodrostat was open labeled 1 mg, 5 mg, 10 mg and 20 mg tablets. |
| LCI699-matching placebo | DRUG | LCI699-matching placebo oral capsules |
| Eplerenone | DRUG | Eplerenone oral capsules |
| Eplerenone-matching Placebo | DRUG | Eplerenone-matching placebo oral capsules |
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...
LCI699 is an investigational small molecule being studied for hypertension, Cushing's disease, essential hypertension, and primary hyperaldosteronism. It is in Phase 2 clinical development and is not yet approved by regulatory authorities.
LCI699 is an aldosterone synthase inhibitor. It works by blocking the enzyme aldosterone synthase, which is involved in the production of aldosterone, a hormone that regulates blood pressure and fluid balance.
LCI699 is being developed by Novartis AG, a multinational pharmaceutical company. Novartis is listed on the New York Stock Exchange under the ticker symbol NVS.
LCI699 is in Phase 2 clinical development. All four clinical trials listed for LCI699 are Phase 2 studies and have been completed. The drug remains investigational and has not received FDA approval.
LCI699 has completed four Phase 2 trials: NCT00732771 in primary hyperaldosteronism, NCT00758524 in essential hypertension, NCT00817635 in resistant hypertension, and NCT01331239 in Cushing's disease. These studies enrolled a total of 826 participants across multiple countries.
LCI699 is also known as osilodrostat. The drug has been studied under the code name LCI699 in clinical trials for hypertension and Cushing's disease, and is referred to as osilodrostat in some contexts.