Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LCI699 · 5 trials · 5 indications
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.
| Arm | Type | Description |
|---|---|---|
| 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 | - |
| Name | Type | Description |
|---|---|---|
| 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 |
Inclusion Criteria: * Patients with a confirmed diagnosis of Cushing's Disease (persistent or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH. * Patients with de novo C...
LCI699 is an investigational small molecule being studied for Cushing's Disease, Essential Hypertension, Primary Hyperaldosteronism, and Hypertension. It is in Phase 2 clinical development and is not approved for any use.
LCI699 is an aldosterone synthase inhibitor. It works by inhibiting 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 stock exchange under the ticker symbol NVS.
LCI699 is in Phase 2 clinical development. It has completed four Phase 2 trials, and all trials are completed. It is not FDA approved and remains an investigational drug.
LCI699 has completed four Phase 2 trials. These include NCT00732771 in Primary Hyperaldosteronism, NCT00817414 and NCT00817635 in Hypertension, and NCT01331239 in Cushing's Disease. All trials are completed.
LCI699 is also known as osilodrostat. It is the same compound, and both names refer to the drug being developed by Novartis for endocrine conditions.