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A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.

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ClinicalTrials.gov Identifier: NCT03277690
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Cortendo AB

Brief Summary:
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous CS previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.

Condition or disease Intervention/treatment Phase
Endogenous Cushing's Syndrome Drug: Levoketoconazole Drug: Placebo Phase 3

Detailed Description:

This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous CS that will assess efficacy, safety, tolerability, and PK of levoketoconazole. There are two populations (cohorts) of subjects: (1) subjects which were previous levoketoconazole study completers and (2) subjects that are levoketoconazole treatment naïve subjects.

Study methodology varies by cohort prior to randomization only. Following initial screening (washout as needed) and Dose Titration and Maintenance Periods, as applicable, this study will be conducted in two double-blind phases (a Withdrawal Phase and a Restoration Phase). The levoketoconazole-naïve cohort will need to go through the Dose Titration and Maintenance Phase. The longest anticipated total study participation duration is approximately 51 weeks.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-Controlled, Randomized Withdrawal Following Open Label Therapy Study to Assess the Safety and Efficacy of Levoketoconazole (2S, 4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome
Actual Study Start Date : September 26, 2017
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Levoketoconazole
Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo
Drug: Levoketoconazole

During the double-blind Withdrawal Phase, patients will receive up to 1200 mg levoketoconazole daily.

During the double-blind Restoration Phase, patients will receive levoketoconazole plus placebo.

Other Name: COR-003

Placebo Comparator: Placebo
Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole
Drug: Placebo

During the double-blind Withdrawal Phase, patients will receive placebo tablets.

During the double-blind Restoration Phase, patients will receive placebo plus levoketoconazole.





Primary Outcome Measures :
  1. Number of subjects with loss of therapeutic response to levoketoconazole upon withdrawing to placebo compared with the proportion of subjects with loss of therapeutic response upon continuing treatment with levoketoconazole. [ Time Frame: max. 9.5 weeks ]
    Urinary free cortisol (UFC) level measurement



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

SONICS STUDY COMPLETERS:

Completed the final SONICS visit (M12) and have demonstrated maintenance of clinical response on a stable Therapeutic Dose of levoketoconazole for at least 12 weeks prior to study entry.

ALL OTHERS:

  • Confirmed newly diagnosed, persistent or recurrent endogenous Cushing's syndrome of any etiology, except secondary to malignancy (including pituitary or adrenal carcinoma).
  • Elevated mean 24-hour UFC levels at least 1.5X upper limit of the normative range of the study's central laboratory assay and from a minimum of three measurements from adequately collected urine.
  • Presence of abnormal values from at least one of these two diagnostic tests:

    • Abnormal Dexamethasone Suppression Test (DST) OR
    • Elevated late night salivary cortisol concentrations (at least two measurements) each greater than the upper limit of the study's central laboratory normative range
  • Non-candidates for CS-specific surgery, refuse surgery or surgery will be delayed until after study completion and agree to complete this study prior to surgery.
  • If post-surgical for CS-specific surgery, then no significant post-operative sequelae remain and the risk of such sequelae is considered negligible.

EXCLUSION CRITERIA:

Subjects will be excluded from the study if ANY of the following criteria are met (NOTE: exclusion criteria apply to and must be assessed in both cohorts):

  • Enrolled in SONICS but have not completed SONICS through Visit M12.
  • Pseudo-Cushing's syndrome based on assessment of the Investigator.
  • Cyclic Cushing's syndrome with multi-week periods of apparent spontaneous CS remission.
  • Non-endogenous source of hypercortisolism, including pharmacological corticosteroids or ACTH.
  • Radiotherapy of any modality directed against the source of hypercortisolism within the last 5 years.
  • Treatment with mitotane within 6 months of enrollment.
  • 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).
  • Clinical or radiological signs of compression of the optic chiasm.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277690


Contacts
Contact: Cortendo AB 610-254-9200 LOGICS@cortendo.com
Contact: Cortendo AB Study Information 610-254-9200 LOGICS@cortendo.com

  Show 45 Study Locations
Sponsors and Collaborators
Cortendo AB
Investigators
Study Director: Steven Schoenfeld, MD Cortendo AB

Responsible Party: Cortendo AB
ClinicalTrials.gov Identifier: NCT03277690     History of Changes
Other Study ID Numbers: COR-2017-01
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cortendo AB:
Cushing Syndrome, Adrenocortical Hyperfunction

Additional relevant MeSH terms:
Syndrome
Cushing Syndrome
Disease
Pathologic Processes
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases