Levoketoconazole

Overview

Cushing's syndrome (CS) is underpinned by chronic hypercortisolism leading to multisystem morbidity, including effects on the cardiovascular and endocrine systems, metabolic syndrome with accompanying changes in body composition, neuropsychiatric effects, changes in blood pressure and chemistry, and opportunistic infections. Ketoconazole has been used both on- and off-label to treat CS due to its ability to inhibit cortisol production. Still, toxicity has limited its use, notably hepatic toxicity and a tendency to prolong the QT interval. Levoketoconazole is one of two enantiomers present in racemic ketoconazole. It possesses most of the inhibitory effect towards steroidogenic enzymes, making it an attractive candidate for CS treatment with a potentially lower toxicity profile than its racemate. Levoketoconazole was approved by the FDA on December 30, 2021, and is currently marketed under the registered trademark RECORLEV by Xeris Pharmaceuticals, Inc.

Indication

Levoketoconazole 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. Levoketoconazole is not indicated for the treatment of fungal infections.

Associated Conditions

Endogenous Cushing's Syndrome

Clinical Trials

Title	Posted	Study ID	Phase	Status	Sponsor
Bioavailability of Levoketoconazole and Ketoconazole Tablets	2019/12/26	NCT04212000	Phase 1	Completed	Cortendo AB
Drug Interaction Study of Levoketoconazole and Metformin	2019/03/19	NCT03880825	Phase 1	Completed	Cortendo AB
Levoketoconazole Food Effect Study in Healthy Subjects	2018/12/07	NCT03768388	Phase 1	Completed	Cortendo AB
Open-label Treatment in Cushing's Syndrome	2018/08/08	NCT03621280	Phase 3	Completed	Cortendo AB
A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.	2017/09/11	NCT03277690	Phase 3	Completed	Cortendo AB
Treatment for Endogenous Cushing's Syndrome	2013/04/24	NCT01838551	Phase 3	Completed	Cortendo AB
Open Label Safety & Pharmacodynamic Study 24Wk w/DIO-902 Combo w/Metformin & Atorvastatin in T2DM Patients	2008/02/22	NCT00622089	Phase 2	Terminated	DiObex
A Phase 2b Study of DIO-902 or DIO-902 Placebo in Addition to Metformin and Atorvastatin or Atorvastatin Placebo for Type 2 Diabetes	2007/07/02	NCT00494663	Phase 2	Terminated	DiObex

FDA Drug Approvals

Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
Recorlev	Xeris Pharmaceuticals, Inc.	72065-003	ORAL	150 mg in 1 1	12/7/2021

EMA Drug Approvals

Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

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