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 |
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Recruitment Status :
Completed
First Posted : September 11, 2017
Results First Posted : November 8, 2022
Last Update Posted : November 8, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Endogenous Cushing's Syndrome | Drug: Levoketoconazole Drug: Placebo | Phase 3 |
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 Pharmacokinetics (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) |
| Actual Enrollment : | 84 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 |
| Actual Primary Completion Date : | June 30, 2020 |
| Actual Study Completion Date : | August 31, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Levoketoconazole
Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo
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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 |
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Placebo Comparator: Placebo
Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole
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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. |
- 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: Loss of therapeutic response is inferred based on mUFC from three 24-hour UFC measurements obtained at any visit from second through final Randomized Withdrawal Phase visits (RW1 through RW5 inclusive) when: (1) mUFC is above 1.5X the ULN of the central laboratory's reference range, OR (2) mUFC is more than 40% above the baseline (RW0) value, if the RW0 value is above the ULN (i.e. >1.0X ULN)1, OR (3) an early rescue criterion is met.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 Urinary Free Cortisol (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.
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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.
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
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| Study Director: | Xavier Valencia, MD | Cortendo AB |
Documents provided by Cortendo AB:
| Responsible Party: | Cortendo AB |
| ClinicalTrials.gov Identifier: | NCT03277690 |
| Other Study ID Numbers: |
COR-2017-01 |
| First Posted: | September 11, 2017 Key Record Dates |
| Results First Posted: | November 8, 2022 |
| Last Update Posted: | November 8, 2022 |
| Last Verified: | October 2022 |
| 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 |
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Cushing Syndrome, Adrenocortical Hyperfunction |
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Cushing Syndrome Syndrome Disease Pathologic Processes |
Adrenocortical Hyperfunction Adrenal Gland Diseases Endocrine System Diseases |