Type 2 diabetes MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: AZD4017
Pharmaceutical Form: Tablet
Other descriptive name: AZD4017
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 800-
Pharmaceutical form of the pl
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Able and willing to provide informed consent 2) Clinical diagnosis of T2DM with HbA1c below or equal to 11% (below or equal to 97 mmol/mol) at screening while taking standard therapy at a stable dose for =10 weeks 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1) Women of child-bearing potential (WOCBP). Note: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >/= 12 consecutive months or women on hormone replacement therapy with documented serum follicle stimulating hormone level >35 mIU/mL]. Additionally, male study participants who are sexually active with a female partner of childbearing potential must be surgically sterilized or agree, along with their partner, to use a highly effective method of birth control (as defined below) from the time of screening until 3 weeks after final dose of study drug (5 drug elimination half-lives plus 2 weeks). Male study participants must also not donate sperm from the time of screening until 3 weeks after final dose of study drug (5 drug elimination half-lives plus 2 weeks). 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 [such as Cerazette™], injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence. 2) Active leg/foot ulceration 3) Acute electrocardiogram (ECG) anomalies deemed to be clinically relevant by the CI 4) Systemic hypertension (BP >150/90) on 3 successive measurements at the screening visit (patients with controlled hypertension can be included in the trial) 5) Any endocrine disorder (other than T2DM), including type 1 or secondary diabetes, except treated hypothyroidism with normal thyroid function tests for at least 3 months 6) Suspicion of or known Gilbert's disease 7) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or alkaline phosphatase (ALP) > 1.5x upper limit of normal (ULN) 8) Bilirubin (total) > 1.5x ULN 9) An eGFR calculated by the Modification of Diet in Renal Disease equation of 2 x ULN 11) Participant is, at the time of signing the informed consent, a user of recreational or illicit drugs (including marijuana) or has had a recent history (within the last year) of drug or alcohol abuse or dependence on questioning or clinical history 12) Receiving any topical, systemic (including vaginal/rectal) or inhaled GC treatment at the time of or within 3 months prior to the screening visit 13) Taking any anticoagulant medication (blood thinning e.g. warfarin) 14) Taking probenicid or similar (for gout) at the time of inquiry 15) Any medical/surgical procedure (excluding skin biopsies) or trauma during IMP administration or within one week following the last administration of the IMP as judged by the CI 16) Involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 17) Participated in any other clinical study within 1 calendar month prior to the screening visit (except registry-only participation) 18) Deemed otherwise inappropriate to participate by the trial team
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We will determine if the treatment is able to achieve it's intended effect (decrease target enzyme activity) in skin of patients with type 2 diabetes;Secondary Objective: 1) Compare the ability of the new treatment to decrease target enzyme activity in skin and at the whole body level 2) Obtain data on the ability of the treatment to reach the skin 3) Asses treatment safety in patient with type 2 diabetes 4) Determine effects of the new treatment on measures of skin function including the role of skin as a barrier against water loss, the ability of skin to retain water (hydration), the ability of nerves in the skin to work correctly, effects on skin thickness and wound healing. We will also examine the underlying causes of these effects by analyzing the levels of all genes in skin. 5) Obtain data on the number of participants that are able to take part, how many participants are recruited and how long it takes to complete recruitment, how many participants that are able to take part agree to taking part, how participants are allocated the treatment or placebo, the ability of participants to take the treatment as instructed, the number of participant;Primary end point(s): 24 hour 11ß-HSD1 activity in skin (efficacy) ;Timepoint(s) of evaluation of this end point: Baseline Visit 1 (day 0) and Visit 4 (day 28). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 24 hour urinary cortisol to cortisone metabolite ratio (days 0 and 35), AZD4017 detection in skin and plasma (day 28), adverse event reporting (days 2, 7, 28, 30 and 35), body mass index, waist-hip ratio and blood pressure (days, 0 and 35) safety blood tests (days 0, 7, 28 and 35), number of patients discontinuing study therapy due to safety (end of trial), sudomotor function and skin hydration (days 0 and 35), epidermal water loss (days 0, 2, 7, 28, 30 and 35), integrity (days 0 and 28, 3 hour, 2 day and 7 day), skin thickness (days 0 and 35), wound healing (days 0 and 28, 2 day and 7 day), RNA-seq gene expression profiling (days 0 and 28), 24 hour urinary free cortisol (days 0 and 35) and feasibility (end of trial).;Secondary end point(s): Additional AZD4017 efficacy variables (24 hour urinary cortisol to cortisone metabolite ratio for systemic 11ß-HSD1 activity and AZD4017 detection in skin and plasma). Safety measures (adverse event reporting, body mass index, waist-hip ratio, blood pressure, blood HbA1c, blood lipids, full blood count, liver function, estimated glomerular filtration rate, kidney function, adrenal function, thyroid function and number of patients discontinuing study therapy due to safety). Skin function measures (sudomotor function and skin hydration, epidermal barrier function, recovery and integrity, skin thickness, wound healing and RNA-seq gene expression profiling). Other measures (24 hour urinary free cortisol for systemic cortisol exposure evaluation). Feasibility (eligibility, recruitment rate, consent rate, assessment of randomization, adherence rate, retention rate, completeness of outcome measure reporting and overall protocol assessment). | — |
Countries
United Kingdom
Contacts
Public ContactAna Tiganescu
University of Leeds
Outcome results
None listed