Adverse effects of prescribed glucocorticoid therapy MedDRA version: 19.0 Level: LLT Classification code 10068501 Term: Cushing's syndrome, steroid-induced System Organ Class: 100000004860
Conditions
Interventions
Product Name: AZD4017
Product Code: AZD4017
Pharmaceutical Form: Tablet
INN or Proposed INN: no INN available
CAS Number: 1024033-43-9
Current Sponsor code: TICSI
Other descriptive name: AZD4017
Conce
Sponsors
University of Oxford, Clinical Trials and Research Governance
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Male volunteers without diabetes (HbA1C 3months • Stable lipid lowering therapy for >3 months • No contraindications to AZD4017 or prednisolone treatment • Study participants who are sexually active with a female partner of childbearing potential must be surgically sterilised, practicing abstinence, or agree, along with their partners, to use two forms of highly effective methods of birth control (i.e. condom plus another highly effective method defined below), and not rely on barrier methods and spermicide alone, from the time of screening until 1 week after final dose of study drug. Male study participants must also not donate sperm from the time of screening until 1 week after final dose of study drug. Highly effective methods of contraception are defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (either oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (either oral [specifically Cerazette], injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Age 60years • Body mass index 30kg/m2 • A diagnosis of diabetes (type 1 or type 2) • A blood haemoglobin ULN • Glucocorticoid therapy (including inhaled, topical or oral) within the last 6 months • Concomitant anti-inflammatory medication including NSAIDs, disease modifying anti-rheumatic drugs (DMARDs) / steroid-sparing medications (e.g. methotrexate, sulphasalzine, hydroxychloroquine, azathioprine, leflunamide, biologics [anti-TNFa, IL-1ra]) • Any medical condition in the opinion of the investigator that might impact upon safety or validity of the results – recent (within 2 weeks) or active infection, known liver disease, known thyroid disease, active malignancy, existing inflammatory condition (e.g. inflammatory athropathy, inflammatory bowel disease, autoimmune disease, connective tissue disease) • Participation in another IMP trial / study within the past 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our main research objectives is… 1. To demonstrate the beneficial effect of the selective 11ß-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in glucose uptake into skeletal muscle and glucose production by the liver. ;Secondary Objective: Our secondary research objectives are... 1. To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone. 2. To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017.;Primary end point(s): The change in glucose disposal as measured during a hyperinsulinaemic euglycaemic clamp. ;Timepoint(s) of evaluation of this end point: Investigations will be performed at baseline and after 7 days of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determine if AZD4017 can limit the detrimental effect of prednisolone (20mg) on hepatic insulin sensitivity as measured across a 2-step hyperinsulinaemic euglycaemic clamp. Define the changes in blood pressure associated with prednisolone and AZD4017 administration Define the changes in adipose tissue and skeletal muscle gene expression profile associated with prednisolone and AZD4017 administration Define the change in whole body oxidation associated with prednisolone and AZD4017 administration. Define the changes in circulating inflammatory cytokines and inflammatory response in circulating inflammatory cells associated with prednisolone and AZD4017 administration. Define the changes in urinary steroid metabolite profile associated with prednisolone and AZD4017 administration. Define the changes in body composition (total and regional lean and fat mass) associated with prednisolone and AZD4017 administration using DXA.;Timepoint(s) of evaluation of this end point: Investigations will be performed at baseline and after 6 or 7 days of treatment | — |
Countries
United Kingdom
Contacts
Public ContactCTRG (via Heather House)
University of Oxford, Clinical Trials and Research Governance
Outcome results
None listed