Endogenous Cushing's SyndromePhase 3NCT03277690
A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.
A Phase 3 study testing Levoketoconazole in people with Endogenous Cushing's Syndrome, run by Cortendo AB at 45 sites in 12 countries.
Trial summary
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous Cushing's Syndrome (CS) previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endogenous Cushing's Syndrome
- What is being tested?
- Levoketoconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 45 sitesin 12 countries
- Study dates
- 26 Sep 2017to 31 Aug 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Presence of abnormal values from at least one of these two diagnostic tests:
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
45 sites in 12 countries.
45 sites in 12 countries
United States13 sites
University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND
Ann Arbor, Michigan, 48109
Emory University, Neurosurgery
Atlanta, Georgia, 30322
Johns Hopkins University, Endocrinology Department
Baltimore, Maryland, 21287
Northwestern University, Medicine - Endocrinology
Chicago, Illinois, 60611
The Center for Diabetes and Endocrine Care
Fort Lauderdale, Florida, 33312
Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital
Los Angeles, California, 90033
Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center
Los Angeles, California, 90048
UCLA School of Medicine, Medicine/Endocrinology Department
Los Angeles, California, 90095
Columbia University, College of P&S Medicine/Neuro-endocrine Unit
New York, New York, 10032
Memorial Sloan Kettering Cancer Center, Endocrinology
New York, New York, 10065
Allegheny Neuroendocrinology Center, West Penn Allegheny Health System
Pittsburgh, Pennsylvania, 15212
Oregon Health & Science University, Neurological Surgery
Portland, Oregon, 97239
Washington University School of Medicine, Endocrinology
St Louis, Missouri, 63110
Italy7 sites
Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche
Ancona, 60126
University of Genova, Department of Internal Medicine & Medical Specialties (DiMI)
Genova, 16132
AOU Policlinico G. Martino Sezione di Endocrinologia
Messina, 98125
AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano)
Naples, 8031
Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology
Roma, 00168
Policlinico Universitario Sant'Andrea, Scienze Mediche
Roma, 00189
AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo
Torino, 10126
Greece5 sites
Evangelismos Athens General Hospital, Department of Endocrinology
Athens, 10676
General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre
Athens, 11527
General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology"
Athens, 11527
University General Hospital of Ioannina, Department of Endocrinology
Ioannina, 45110
Hippokration General Hospital, "Endocrinology and Diabetes Department
Thessaloniki, 54642
Romania4 sites
Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie
Bucharest, 011863
Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie
Cluj-Napoca, 400349
Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie
Târgu Mureş, Mureș County, 540072
Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie
Timișoara, Timiș County, 300723
Bulgaria3 sites
Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases
Sofia, 1431
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases
Sofia, 1431
University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika
Sofia, 1431
Israel3 sites
Bnai Zion Medical Center, Institute of Endocrinology
Haifa, 34802
Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus"
Petah Tikva, 49100
Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension
Tel Aviv, 642-3906
Poland3 sites
Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department
Gliwice, 44-101
Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych
Lodz, 93-338
Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych
Warsaw, 04-141
Netherlands2 sites
Leiden University, Leiden University Medical Center, Department of Endocrinology
Leiden, 2333ZA
Erasmus Medical Center, Department of Internal Medicine
Rotterdam, 3015CE
Spain2 sites
Hospital Universidad De La Ribera, Endocrinologia
Alzira, Valencia, 46600
Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition
Madrid, 28034
Denmark1 site
Rigshospitalet, Copenhagen University Hospital, Endocrinology Department
Copenhagen, 2100
France1 site
APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques
Marseille, Cedex 5, 13385
Hungary1 site
Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor
Budapest, 1088
About this study
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
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous Cushing's Syndrome (CS) previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.
Read the 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 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.
- Conditions
- Endogenous Cushing's Syndrome
- Being tested
- Levoketoconazole, Placebo
- Keywords
- Cushing Syndrome, Adrenocortical Hyperfunction
- Medical subject headings
- Cushing Syndrome, Adrenocortical Hyperfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevoketoconazoleDrug
Also called COR-003
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.
PlaceboDrug
During the double-blind Withdrawal Phase, patients will receive placebo tablets.
During the double-blind Restoration Phase, patients will receive placebo plus levoketoconazole.
| Study group | Role | What they receive |
|---|---|---|
| Levoketoconazole | Experimental | Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo Receives: Drug: Levoketoconazole |
| Placebo | Placebo comparator | Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: max. 9.5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start26 Sep 2017
- Primary completion30 Jun 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endogenous Cushing's SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cortendo AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xavier Valencia, MD, Study director, Cortendo AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03277690
- Sponsor's protocol ID
- COR-2017-01
- Status last verified
- Oct 2022
- First submitted
- 7 Sep 2017
- Last updated
- 8 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03277690
- Acronym / sponsor ID
- COR-2017-01
- Conditions
- Endogenous Cushing's Syndrome
- Keywords
- Cushing Syndrome, Adrenocortical Hyperfunction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Cortendo ABIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2017 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 11 Sep 2017 (actual)
- Results
- Posted 8 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous Cushing's Syndrome (CS) previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levoketoconazole | Experimental | Drug: LevoketoconazoleDouble blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo |
| Placebo | Placebo comparator | Drug: PlaceboDouble blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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.
- Presence of abnormal values from at least one of these two diagnostic tests:
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevoketoconazoleAlso: COR-003During 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. | Drug | Levoketoconazole |
| PlaceboDuring the double-blind Withdrawal Phase, patients will receive placebo tablets. During the double-blind Restoration Phase, patients will receive placebo plus levoketoconazole. | Drug | Placebo |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Valencia, MD study director
Cortendo AB
45 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levoketoconazole in people with Endogenous Cushing's Syndrome, run by Cortendo AB at 45 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Italy, Greece, Romania, Bulgaria and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.