A Study to Assess Levoketoconazole in the Treatment of Endogenous Cushing’s Syndrome
- Conditions
- Endogenous Cushing´s syndrome (CS)MedDRA version: 20.0Level: LLTClassification code 10011657Term: Cushings syndromeSystem Organ Class: 100000004860Therapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2017-004647-20-NL
- Lead Sponsor
- Cortendo AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 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:
- 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
- Surgically sterile with documented hysterectomy and/or bilateral oophorectomy or tubal ligation.
OR
- 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.
Fertile men must also agree to use a highly effective method of birth control while participating in the study and for 90 days after the last dose of levoketoconazole. Abstinence is considered acceptable birth control if routinely practiced.
3. Able to comprehend and comply with procedures.
Are the trial subjects under 18
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 for treatment of CS or received surgical treatment of CS within the 6 weeks prior to Screening.
5. Had non-CS major surgery within 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, well-differentiated 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 the Screening requiring medical intervention (may be eligible once stable, to be determine 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.
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 following:
- Drugs used to treat Cushing’s Syndrome;
- Weight loss medications (prescription or over the counter);
- Acetaminophen (paracetamol) above 2 g total daily dose;
- Strong inducers or inhibitors of CYP3A4
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method