An Open-Label Extension Study of Levoketoconazole (2S,4R-ketoconazole) in the Treatment of Endogenous Cushing*s Syndrome

Phase 3

Recruiting

• Conditions: Endogenous Cushings syndrome; 10001353

• Registration Number: NL-OMON49258
• Lead Sponsor: Cortendo AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 2

Inclusion Criteria

To be eligible for participation in this study, subjects for whom the
investigator believes long-term use of levoketoconazole may be beneficial must
meet ONE of the following 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: Subjects meeting criteria 1 or 2 above who have had a break in therapy
may be eligible
only after discussion with the Medical Monitor. If eligible, such subjects may
require re-establishment of the Therapeutic Dose via titration. All subjects
who have had a break in therapy should be discussed with the Medical Monitor to
determine the starting dose of levoketoconazole.
Prior to resuming treatment with levoketoconazole, other therapies for
Cushing*s syndrome
must undergo an appropriate washout period, with minimum washout durations as
follows:
* Ketoconazole or metyrapone: 2 weeks;
* Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks);
* Octreotide acetate LAR, lanreotide Autogel®, pasireotide LAR: 12 weeks;
* Lanreotide SR: 8 weeks;
* Octreotide acetate (immediate release) or short-acting pasireotide: 1 week;
* Mifepristone (RU 486, KORLYM®): 4 weeks;
* Megestrol acetate or medroxyprogesterone acetate (and selected other synthetic
progestins): 6 weeks.
3. Currently in a named patient program or other Expanded Access Program
receiving
levoketoconazole.
4. Were levoketoconazole-naïve prior to entry and received early rescue therapy
with open-label
levoketoconazole in Study COR-2017-01.
5. Achieved a clinically meaningful partial response (with reduction in UFC) in
Study COR-2017-01 at dose level 7 or at a maximally tolerated dose of
levoketoconazole but did not meet the randomization criteria for Study
COR-2017-01 at the end of the Dose Titration and Maintenance Phase when
randomization was open.
6. Were levoketoconazole-naïve prior to entry and were enrolled in Study
COR-2017-01 in the Dose
Titration and Maintenance Phase when randomization was closed. (NOTE: Such
subjects must receive at least 1 dose levoketoconazole before transitioning to
this study.), In addition, subjects must meet ALL the following criteria:
1. Willing to participate and able to provide written informed consent prior to
any study procedures
being performed; eligible subjects must be able to understand the informed
consent form prior to
inclusion into the study.
2. A female is eligible to enter and participate in the study if she is:
3. Postmenopausal, defined as age 50 years or older with amenorrhea for more
than 1 year or any age with serum follicle stimulating hormone (FSH) at least
23 mIU/mL and estradiol no more
than 40 pg/mL (140 pmol/L) (NOTE: laboratory values obtained during COR-2012-01
or COR-
2017-01 protocol will be utilized).
OR
4. Surgically sterile*documented hysterectomy and/or bilateral oophorectomy or
tubal ligation.
OR
5. Of child-bearing potential and agrees to use a highly effective method of
birth control while
participating in the study and for 30 days after the last dose of
levoketoconazole. Abstinence is
considered acceptable birth control if routinely practiced.
Cortendo AB Protocol COR-2017-OLE
Amendment 1 19 July 2018 Page 10 of 95 CONFIDENTIAL
Fertile men must also agree to use a hig

Exclusion Criteria

Subjects will not be eligible for participation in the study if ANY of the
following criteria are met:
1. Discontinued levoketoconazole while participating in Study COR-2012-01 or
Study COR-2017-01
or a named patient program or other Expanded Access program, due to safety or
tolerability
concerns or lack of efficacy.
2. Pregnant, lactating or intend to conceive while receiving levoketoconazole.
3. Have a medical condition or other circumstances that, in the opinion of the
Investigator, might
interfere with the subject*s participation or pose unacceptable risk to the
subject.
4. Scheduled for surgical treatment of CS or received surgical treatment of CS
within the 6 weeks
prior to Screening.
5. Had non-CS major surgery within the 4 weeks prior to Screening.
6. Treated with mitotane within 6 months prior to enrollment.
7. History of malignancy, including adrenal or pituitary carcinomas (other than
low-risk, welldifferentiated
carcinomas of thyroid, breast or prostate that are very unlikely to require
further
treatment in the opinion of the treating physician, or squamous cell or basal
cell carcinoma of the
skin).
8. QTc interval greater than 470 msec via central-reader interpretation during
Screening.
9. Clinically significant abnormality in 12-lead electrocardiogram (ECG) during
Screening requiring
medical intervention (may be eligible once stable, to be determined case by
case).
10. Clinical or radiological signs of compression of the optic chiasm newly
apparent since enrolling in
a parent study.
11. Liver safety tests during the Screening Phase as follows:
* ALT and/or AST above 3X ULN (NOTE: transaminase values up to 5X ULN may be
allowed
on an exceptional basis for subjects who have exhibited stable values for at
least 3 months)
* AP or TBN above 2X ULN.
o Subjects with isolated indirect TBN up to 3X ULN that are presumed to have
Gilbert*s
syndrome may be enrolled if all other liver safety tests are within normal
levels.
12. Decreased renal function as defined by eGFR below 40 mL/min/1.73 m2, using
MDRD equation
for eGFR.
13. Serum potassium below 3.9 mEq/L (may be supplemented to achieve 3.9 mEq/L
or above).
14. Abnormal free thyroxine (FT4), unless subsequently corrected and stable for
at least 4 weeks.
Subjects with thyroid stimulating hormone (TSH) less than the lower limit of
normal (LLN) and
normal FT4 are potentially eligible without intervention.
15. Abused alcohol or drugs since enrolling in a parent study (in the
Investigator*s opinion).
16. Currently participating in another study or has received any
investigational treatment (drug,
biological agent or device) other than levoketoconazole, within prior 30 days
of the Screening visit
or five half-lives of treatment, whichever is longer.
17. Current use of any H2-receptor antagonists, proton-pump inhibitors, or
sucralfate (all inhibit
absorption of levoketoconazole; subjects may be allowed to enroll after
washout). [NOTE: A list
of acceptable oral antacids will be provided; if used, antacids must be
ingested at least 2 hours after
dosing of levoketoconazole.]
18. Current use of any prohibited concomitant medication that cannot be
discontinued safely and
washed out completely prior to the Baseline Visit, including but not limited to
the fo

Study & Design

• Study Type: Interventional
• Study Design: Not specified