Clinical trial NCT03621280: Open-label Treatment in Cushing's Syndrome
Official title: An Open-label Extension Study of Levoketoconazole (2S,4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cushing Syndrome
Cushing Disease
Lead sponsor: Cortendo AB
Sponsor class: INDUSTRY
First posted: 2018-08-08
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-Label Extension Study
Primary purpose: TREATMENT

Brief summary: This is a long-term, open-label extension study of levoketoconazole in subjects with endogenous Cushing's Syndrome.

Detailed description: This is a long-term, OLE study of levoketoconazole in subjects with endogenous CS who have completed one or both parent studies or otherwise potentially qualify for this study, as defined in the eligibility criteria.

Eligibility criteria: Inclusion 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 of 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 of levoketoconazole before transitioning to this study.)

Exclusion Criteria:

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. Scheduled for surgery for treatment of CS or received surgery for treatment of CS within the 6 weeks prior to Screening.
3. Treated with mitotane within 6 months prior to enrollment.
4. 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).

Primary outcomes:
measure: Changes from Baseline in 24-h UFC
timeFrame: From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
measure: Changes from Baseline in Late Night Salivary Cortisol
timeFrame: From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
measure: Changes from Baseline in AEs/SAEs/AESI as assessed by CTCAE V4.03
timeFrame: From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico HSC - HSC Sponsored Projects Office
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Plovdiv
country: Bulgaria
facility: Sveti Georgy University Hospital Clinic of Endocrinology and Metabolic Diseases
city: Sofia
country: Bulgaria
facility: Alexandovska University Hospital
city: Sofia
country: Bulgaria
facility: University Specialized Hospital for Active Treatment in Endocrinology
city: Marseille
country: France
facility: APHM Hôpital de la Conception
city: Athens
country: Greece
facility: General Hospital of Athens Evangelismos Department of Endocrinology and Diabete
city: Thessaloníki
country: Greece
facility: Hippokration General Hospital Endocrinology and Diabetes Department
city: Budapest
country: Hungary
facility: Semmelweis Egyetem II. Belgyógyászati Klinika
city: Haifa
country: Israel
facility: Bnai Zion Medical Center Endocrinology Institute
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Beilinson Campus
city: Tel Aviv
country: Israel
facility: Tel Aviv-Sourasky Medical Center Institute Endocrinology Metabolism & Hypertension
city: Ancona
country: Italy
facility: Clinica Endocrinologia malattie del Metabolismo
city: Messina
country: Italy
facility: AOU Policlinico G. Martino Sezione di Endocrinologia
city: Naples
country: Italy
facility: Via Sergio Pansini 5 Uni Naples FedericoII Dept of Molecular&Clinical Endocrinology&Oncology
city: Roma
country: Italy
facility: Policlinico Universitario Sant'Andrea
city: Turin
country: Italy
facility: University of Turin
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Cluj-Napoca
country: Romania
facility: Institutul National de Endocrinologie C.I. Parhon
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca
city: Târgu-Mureş
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Alzira
country: Spain
facility: Hospital Universidad De La Ribera
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: Cortendo AB
name: Fredric Cohen, MD
role: STUDY_CHAIR
References: