UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Investigator-initiated phase I/IIa clinical trial to assess the safety and efficacy of 11beta-HSD1 inhibitor in patients with the refractory Cushing syndrome and subclinical Cushing syndrome.
Title of the study (Brief title)	Investigator-initiated clinical trial for 11beta-HSD1 inhibitor.
Region	Japan

Condition
Condition	The refractory Cushing syndrome and subclinical Cushing syndrome.
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Evaluation of efficacy of 11beta-HSD1 inhibitor on glucose tolerance.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	To assess the response rate in AUCglucose during oral glucose tolerance test at Week 24.
Key secondary outcomes	To assess the percent change from baseline in AUCglucose during oral glucose tolerance test at Week 24. To assess the response rate and percent change from baseline in AUCglucose during oral glucose tolerance test at Week 12. To assess the absolute and percent change from baseline in the following values. Blood cortisol concentration, Urine cortisol, Salivary cortisol concentration, HbA1c, HOMA-IR, Diastolic and systolic blood pressure

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification	NO
Dynamic allocation	NO
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Oral administration of 200mg of 11beta-HSD1 inhibitor after dinner once a day for 12 weeks. After confirming the safety of the study, oral administration continues further 12 weeks. In case of the subjects with insufficient effect, administration dose will be increased to 400mg b.i.d for further 12 week.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Include the patients who match the following 8 criteria. 1) The patients with the age of 18 y ears old or more. 2) The patients diagnosed with the refractory Cushing syndrome or the subclinical Cushing syndrome. 3) The patients with impaired glucose tolerance or type 2 diabetes who are treated with alpha glucosidase inhibitor or diet exercise therapy. 4) The patients with HbA1c in the screening test less than 8.0 percent and with no change in the diabetes drug for at least 2 M prior to the study. 5) The patient who are capable of oral administration of the drug. 6) In case of men, the patients who agree to contraception or diagnosed with azoospermia. 7) In case of women, the patients who agree to contraception or diagnosed with infertility. 8) The patients who written consent has been obtained.
Key exclusion criteria	Exclude the patients who correspond to any of the following 12 criteria. 1) Patients with sever heart or blood diseases. 2) Patient with a high degree of renal dysfunction (eGFR<30mL/min/1.73 m2) 3) Patients with liver dysfunction (AST or ALT> 3x Upper limit ) 4) Patients with acute or chronic infection that require treatment. 5) Patients with autoimmune or allergy diseases that require treatment. 6) Patients with present or a history of less than 5 years of malignancy with exception of ectopic ACTH syndrome. 7) Patients receiving metyrapone or trilostane within 1 week or mitotane within 3 months before first dose of 11beta-HSD1 inhibitor. 8) Patients with a history of drug allergies that interfere with participation in the clinical trial. 9) Patients with mental illness or its history that interfere with participation in the clinical trial. 10) Pregnant women, nursing mothers, or patients who do not agree to contraception during study period. 11) Patients participating in other clinical trial or clinical research and receiving the drug within 30 days before obtaining informed consent. 12) Patients who are deemed to be inappropriate by investigator or sharing physician from a medical point of view.
Target sample size	16

Research contact person
Name of lead principal investigator	Masatoshi Nomura
Organization	Kyushu University Hospital
Division name	Department of endocrine, metabolism and diabetes
Address	Maidashi 3-1-1, Higashi-ku, Fukuoka
TEL	092-642-5293
Email	nomura@med.kyushu-u.ac.jp

Public contact
Name of contact person	Kenji Ashida
Organization	Kyushu University Hospital
Division name	Department of endocrine, metabolism and diabetes
Address	Maidashi 3-1-1, Higashi-ku, Fukuoka
TEL	092-642-5293
Homepage URL
Email	ashida@med.kyushu-u.ac.jp

Sponsor
Institute	Kyushu University Hospital
Institute
Department

Funding Source
Organization	Japan Agency of Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	九州大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 12 Day

Progress
Recruitment status	Preinitiation
Date of protocol fixation	2016 Year 09 Month 07 Day
Anticipated trial start date	2016 Year 11 Month 15 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 10 Month 19 Day
Last modified on	2016 Year 10 Month 19 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028177