Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Levoketoconazole · 5 trials · 5 indications
Proportions of participants with mUFC: 1) Less or equal to the ULN of the reference range, 2) Above the ULN to 1.5x the ULN, and 3) Above 1.5x the ULN.
Urinary free cortisol (UFC) level measurement: Loss of therapeutic response is inferred based on mUFC from three 24-hour UFC measurements obtained at any visit from second through final Randomized Withdrawal Phase visits (RW1 through RW5 inclusive) when: (1) mUFC is above 1.5X the ULN of the central laboratory's reference range, OR (2) mUFC is more than 40% above the baseline (RW0) value, if the RW0 value is above the ULN (i.e. \>1.0X ULN)1, OR (3) an early rescue criterion is met.
The response to COR-003 is defined as mean UFC concentration ≤ULN following 6 months of maintenance phase therapy without a prior dose increase during that phase. The proportion of responders at the End of Maintenance Phase visit, following 6 months of treatment in the Maintenance Phase, for all dose groups combined was estimated using a generalized linear model with repeated measurements based on a binomial distribution with a logit link function and with region (US vs. non-US), concurrent CS medical conditions (diabetes \[Yes/No\], hypertension \[Yes/No\]), age (rounded median split based on the ITT population), sex, disease duration (years), prior CS medication (Yes/No), prior radiation therapy (Yes/No) as Baseline covariates and visit as an independent factor. The least squares mean (LSMEAN) estimate of the UFC response after 6 months of treatment in the Maintenance Phase alongside its 95% Wald CI is presented.
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
Point estimates and 90 percent (%) confidence intervals (CIs) for the dose-normalized ratios of geometric least squares means between Test (levoketoconazole) and Reference (ketoconazole)
Maximum observed plasma concentration (Cmax) of levoketoconazole for fed vs. fasted condition
Time to maximum concentration (Tmax) of levoketoconazole for fed vs. fasted condition
Apparent Terminal Elimination Phase Rate Constant (λz) of levoketoconazole for fed vs. fasted condition
Terminal phase half-life (t 1/2) of levoketoconazole for fed vs. fasted condition
Area under the plasma concentration-time curve (AUC) from time 0 to time of last measurable plasma concentration (AUClast) and from time 0 extrapolated to infinity (AUCinf) of levoketoconazole for fed vs. fasted condition
| Arm | Type | Description |
|---|---|---|
| Levoketoconazole | EXPERIMENTAL | Levoketoconazole taken twice daily up to 1200 mg daily |
| Placebo | PLACEBO_COMPARATOR | Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole |
| Levoketoconazole DL0 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 0 Once Daily |
| Levoketoconazole DL1 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 1 Twice Daily |
| Levoketoconazole DL2 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 1 Twice Daily |
| Levoketoconazole DL3 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 3 Twice Daily |
| Levoketoconazole DL4 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 4 Twice Daily |
| Levoketoconazole DL5 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 5 Twice Daily |
| Levoketoconazole DL6 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 6 Twice Daily |
| Levoketoconazole DL7 | EXPERIMENTAL | Levoketoconazole Tablets Dose Level 7 Twice Daily |
| Ketoconazole | ACTIVE_COMPARATOR | Ketoconazole 200 mg |
| Fasting State | OTHER | A single 600 mg dose of levoketoconazole administered in a fasting state. |
| Fed State | OTHER | A single 600 mg dose of levoketoconazole administered in a fed state. |
| Name | Type | Description |
|---|---|---|
| Levoketoconazole | DRUG | Levoketoconazole up to 1200 mg daily |
| Placebo | DRUG | During the double-blind Withdrawal Phase, patients will receive placebo tablets. During the double-blind Restoration Phase, patients will receive placebo plus levoketoconazole. |
| Ketoconazole | DRUG | Ketoconazole tablet |
Key Inclusion Criteria: 1. Completed the Extended Evaluation Phase of Study COR-2012-01 (i.e. M12) 2. Completed the Restoration Phase of Study COR-2017-01 (i.e. RES2) NOTE: Participants meeting criteria 1 or 2 above who have had a break in therapy may be eligible only after discussion with the ...
Levoketoconazole is an investigational small molecule being developed for the treatment of endogenous Cushing's syndrome, a condition caused by excess cortisol production. It is also being studied in healthy subjects for bioavailability purposes. The drug is currently in Phase 3 clinical development and has not been approved by regulatory authorities.
Levoketoconazole is being developed by Xeris Biopharma Holdings, Inc., a company traded on the stock exchange under the ticker symbol XERS. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with endogenous Cushing's syndrome.
Levoketoconazole is in Phase 3 clinical development for endogenous Cushing's syndrome. It remains an investigational drug and has not received FDA approval. Several Phase 3 trials have been completed, but the drug is still undergoing clinical evaluation to determine its safety and effectiveness.
Levoketoconazole has been studied in several completed clinical trials, including NCT01838551 and NCT03277690, both Phase 3 studies in endogenous Cushing's syndrome. An additional Phase 3 open-label trial, NCT03621280, and a Phase 1 bioavailability study, NCT04212000, have also been completed. These trials enrolled a total of 178 participants.
Levoketoconazole is a small molecule that targets cortisol production. It works by inhibiting enzymes involved in steroidogenesis, thereby reducing cortisol levels in the body. This mechanism is intended to address the underlying hormonal imbalance in endogenous Cushing's syndrome.
Levoketoconazole is a distinct drug from ketoconazole, though they are related compounds. A Phase 1 study (NCT04212000) compared the bioavailability of levoketoconazole and ketoconazole tablets in healthy subjects. Levoketoconazole is being developed specifically for endogenous Cushing's syndrome.