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Open-label Treatment in Cushing's Syndrome

Phase 3
Completed
Conditions
Cushing Syndrome
Cushing Disease
Interventions
Registration Number
NCT03621280
Lead Sponsor
Cortendo AB
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
51
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LevoketoconazoleLevoketoconazoleLevoketoconazole taken twice daily up to 1200 mg daily
Primary Outcome Measures
NameTimeMethod
Changes from Baseline in 24-h UFCFrom Baseline to final study visit or up to a maximum of 3 years, whichever comes first.

Changes or shifts from baseline in mUFC

Changes from Baseline in Late Night Salivary CortisolFrom Baseline to final study visit or up to a maximum of 3 years, whichever comes first.

Changes or shifts from baseline in late night salivary cortisol levels

Changes from Baseline in AEs/SAEs/AESI as assessed by CTCAE V4.03From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.

Changes from Baseline in the incidence and severity of AEs, SAEs, AESIs

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (30)

Columbia University Medical Center

🇺🇸

New York, New York, United States

APHM Hôpital de la Conception

🇫🇷

Marseille, France

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Clinica Endocrinologia malattie del Metabolismo

🇮🇹

Ancona, Italy

Sveti Georgy University Hospital Clinic of Endocrinology and Metabolic Diseases

🇧🇬

Plovdiv, Bulgaria

Alexandovska University Hospital

🇧🇬

Sofia, Bulgaria

Bnai Zion Medical Center Endocrinology Institute

🇮🇱

Haifa, Israel

Spitalul Clinic Judetean Mures

🇷🇴

Târgu-Mureş, Romania

Emory University

🇺🇸

Atlanta, Georgia, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

The Center for Diabetes and Endocrine Care

🇺🇸

Fort Lauderdale, Florida, United States

University of New Mexico HSC - HSC Sponsored Projects Office

🇺🇸

Albuquerque, New Mexico, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

University Specialized Hospital for Active Treatment in Endocrinology

🇧🇬

Sofia, Bulgaria

Policlinico Universitario Sant'Andrea

🇮🇹

Roma, Italy

General Hospital of Athens Evangelismos Department of Endocrinology and Diabete

🇬🇷

Athens, Greece

Tel Aviv-Sourasky Medical Center Institute Endocrinology Metabolism & Hypertension

🇮🇱

Tel Aviv, Israel

Hippokration General Hospital Endocrinology and Diabetes Department

🇬🇷

Thessaloníki, Greece

Semmelweis Egyetem II. Belgyógyászati Klinika

🇭🇺

Budapest, Hungary

Rabin Medical Center, Beilinson Campus

🇮🇱

Petah tikva, Israel

AOU Policlinico G. Martino Sezione di Endocrinologia

🇮🇹

Messina, Italy

Via Sergio Pansini 5 Uni Naples FedericoII Dept of Molecular&Clinical Endocrinology&Oncology

🇮🇹

Naples, Italy

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

University of Turin

🇮🇹

Turin, Italy

Institutul National de Endocrinologie C.I. Parhon

🇷🇴

Cluj-Napoca, Romania

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Łódź, Poland

Hospital Universidad De La Ribera

🇪🇸

Alzira, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Spain

Spitalul Clinic Judetean de Urgenta Cluj-Napoca

🇷🇴

Cluj-Napoca, Romania

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