Clinical Trial Results:
An Open-label Extension Study of Levoketoconazole (2S,4R-ketoconazole) in the Treatment of Endogenous Cushing’s Syndrome
|
Summary
|
|
EudraCT number |
2017-004647-20 |
Trial protocol |
HU BG ES IT NL GR RO |
Global end of trial date |
30 Dec 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
08 Aug 2025
|
First version publication date |
08 Aug 2025
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
COR-2017-OLE
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03621280 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Cortendo AB subsidiary of Xeris Biopharma Holdings
|
||
Sponsor organisation address |
1375 West Fulton Street, Suite 1300, Chicago, Illinois, United States, 60607
|
||
Public contact |
Clinical Trial Information, Valentina Conoscenti, +1 877-937-4737, clinicaltrials@xerispharma.com
|
||
Scientific contact |
Clinical Trial Information, Valentina Conoscenti, +1 877-937-4737, clinicaltrials@xerispharma.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
02 Mar 2023
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
30 Dec 2022
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
30 Dec 2022
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To assess long-term safety and efficacy durability of levoketoconazole as chronic treatment for endogenous Cushing’s Syndrome (CS).
|
||
Protection of trial subjects |
The study was designed, conducted, and monitored in accordance with the ethical principles set forth in the Declaration of Helsinki and the Guideline for ICH GCP (ICH E6). It also complied with the obligations and requirements of clinical investigators and all other requirements listed in 21 Code of Federal Regulations (CFR) 312. The Investigators conducted all aspects of this study in accordance with all national, state, and local laws of the pertinent regulatory authorities as well as the study procedures provided by Cortendo AB.
|
||
Background therapy |
There were no required or specified background therapies for this study. | ||
Evidence for comparator |
The study was an open-label extension where all participants received levoketoconazole. | ||
Actual start date of recruitment |
07 Jan 2019
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 4
|
||
Country: Number of subjects enrolled |
Poland: 2
|
||
Country: Number of subjects enrolled |
Romania: 3
|
||
Country: Number of subjects enrolled |
Spain: 2
|
||
Country: Number of subjects enrolled |
Bulgaria: 9
|
||
Country: Number of subjects enrolled |
France: 2
|
||
Country: Number of subjects enrolled |
Greece: 5
|
||
Country: Number of subjects enrolled |
Hungary: 2
|
||
Country: Number of subjects enrolled |
Italy: 6
|
||
Country: Number of subjects enrolled |
United States: 10
|
||
Country: Number of subjects enrolled |
Israel: 6
|
||
Worldwide total number of subjects |
51
|
||
EEA total number of subjects |
35
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
47
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||
Recruitment details |
The study was conducted in the United States, Israel, and Europe. Participants were recruited starting on 07Jan2019 through 03Dec2020 based on prior participation in COR-2012-01 and/or COR-2017-01. Participant eligibility was assessed prior to enrollment. 52 potential participants were screened and 51 participants were enrolled. | ||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||
Screening details |
The study was a long-term open-label extension study of levoketoconazole in participants with endogenous Cushing's Syndrome who had completed one or both parent studies (COR-2012-01 and/or COR-2017-01) or participated in one of the parent studies and met specified inclusion criteria. | ||||||||||||||||||
|
Period 1
|
|||||||||||||||||||
Period 1 title |
Treatment (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
|
Arm title
|
Levoketoconazole | ||||||||||||||||||
Arm description |
Establishment and treatment with a therapeutic dose of levoketoconazole (up to a dose of 1200 mg daily) based on normalization of mean urinary free cortisol (mUFC). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Levoketoconazole
|
||||||||||||||||||
Investigational medicinal product code |
COR-003
|
||||||||||||||||||
Other name |
Recorlev
|
||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
A single strength levoketoconazole tablet, 150 mg, was provided for oral administration. Individualized dosing for participants was established with dosing administered once or twice daily to achieve one of the following total daily doses: 150 mg, 300 mg, 450 mg, 600 mg, 750 mg, 900 mg, 1050 mg, 1200 mg.
|
||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Levoketoconazole
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Establishment and treatment with a therapeutic dose of levoketoconazole (up to a dose of 1200 mg daily) based on normalization of mean urinary free cortisol (mUFC). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Levoketoconazole
|
||
Reporting group description |
Establishment and treatment with a therapeutic dose of levoketoconazole (up to a dose of 1200 mg daily) based on normalization of mean urinary free cortisol (mUFC). | ||
Subject analysis set title |
Original Baseline
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The Original Baseline is the baseline value of mUFC relative to the ULN for the very first parent study (COR-2012-01 or COR-2017-01) that the participant was enrolled into.
|
||
Subject analysis set title |
OLE Baseline
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The OLE Baseline is the data from the participants that had an evaluable baseline mUFC at the start of COR-2017-OLE.
|
||
Subject analysis set title |
Month 6
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 6 is the data from participants that had an evaluable mUFC at the Month 6 analysis timepoint in COR-2017-OLE.
|
||
Subject analysis set title |
Month 12
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 12 is the data from participants that had an evaluable mUFC at the Month 12 analysis timepoint in COR-2017-OLE.
|
||
Subject analysis set title |
Month 18
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 18 is the data from participants that had an evaluable mUFC at the Month 18 analysis timepoint in COR-2017-OLE.
|
||
Subject analysis set title |
Month 24
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 24 is the data from participants that had an evaluable mUFC at the Month 24 analysis timepoint in COR-2017-OLE.
|
||
Subject analysis set title |
Month 30
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 30 is the data from participants that had an evaluable mUFC at the Month 30 analysis timepoint in COR-2017-OLE.
|
||
Subject analysis set title |
Month 36
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Month 36 is the data from participants that had an evaluable mUFC at the Month 36 analysis timepoint in COR-2017-OLE.
|
||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Proportion of Participants with Mean Urinary Free Cortisol (mUFC) Categorization Based on Upper Limit of Normal (ULN) [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From parent study Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The key exploratory endpoint (identified as the primary endpoint for this study) was an mUFC categorization based on ULN at specified visits. At each visit the number of subjects in the following categories were summarized for mUFC: 1) mUFC less than or equal to the ULN, 2) mUFC above the ULN to 1.5x ULN, and 3) mUFC above 1.5x ULN. No formal analysis was performed. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 3 years; from start of treatment through end of study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All participants
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Jul 2018 |
Key changes included the removal of the Data Monitoring Committee requirement for the study, updated inclusion of participants who completed COR-2012-01 or COR-2017-01 but had a break in therapy (this included adding information about the washout periods for drugs taken for Cushing's Syndrome and updating the timing of screening and baseline assessments for these participants), updating the language for the management of QTc interval prolongation. |
||
23 Sep 2019 |
Key changes to the protocol included the addition of information to allow the enrollment of participants from COR-2017-01 that were enrolled in the dose titration phase of that study at the time entry into it's randomized-withdrawal phase was closed, additional clarification was also included for participants that had a gap in treatment prior to participating in COR-2017-OLE, and inclusion of an allowance (with Medical Monitor agreement) for a break in therapy while participating in the study. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The protocol defined all efficacy endpoints as exploratory; however, the endpoint presented in this summary of results was the endpoint identified as the key exploratory endpoint. | |||
