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Label indication RECORLEV is indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Limitations of Use RECORLEV is not approved for the treatment of fungal infections. The safety and effectiveness of RECORLEV for the treatment of fungal infections have not been established. FDA label
Also known as COR-003
levoketoconazole · 3 trials · 3 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.
| 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 |
| 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. |
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 Cushing syndrome, including endogenous Cushing's syndrome. It is intended for adults 18 years and older. It is not yet approved and remains in clinical development.
Levoketoconazole is an inhibitor of the CYP11B2, CYP17A1, CYP11A1, and CYP11B1 enzymes. By inhibiting these cytochrome P450 enzymes involved in steroid synthesis, it is designed to reduce cortisol production, which is the goal of treating endogenous Cushing's syndrome.
Levoketoconazole is being developed by Xeris Biopharma Holdings, Inc., which trades on the Nasdaq under the ticker XERS. The company is the sponsor of the clinical program evaluating the drug in Cushing syndrome and endogenous Cushing's syndrome.
Levoketoconazole is in Phase 3 development. It is investigational and has not been approved by the FDA. The Phase 3 program in Cushing syndrome and endogenous Cushing's syndrome has been completed, with no trials currently active.
Three completed Phase 3 trials have evaluated levoketoconazole: NCT03621280 in Cushing syndrome and Cushing disease, NCT03277690 in endogenous Cushing's syndrome, and NCT01838551 in endogenous Cushing's syndrome. Together they enrolled 229 adults across sites in the United States, Europe, Canada, Israel, and Turkey.
Levoketoconazole is the levorotatory enantiomer of ketoconazole, meaning it is a single enantiomer rather than the racemic mixture found in ketoconazole. It is being developed as a distinct small molecule product for endogenous Cushing's syndrome.