Type2 Diabetes
Conditions
Keywords
Type 2 Diabetes, Diabetes mellitus, GABAA receptor, β-cell function, glycemic control
Brief summary
The aim of this single-center, prospective, randomized, double-blind, placebo-controlled, 2-arm parallel-group interventional study is to investigate the effect of 4-week treatment with AP-325 on C-peptide release as measure of insulin secretion compared to placebo in type 2 diabetes (T2D) patients.
Interventions
DRUGAP-325
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.
DRUGPlacebo matching AP-325
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.
Sponsors
Algiax Pharmaceuticals GmbH
The Deutsche Diabetes Forschungsgesellschaft e.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of T2D * Age between 25 and 75 years * HbA1c ≥6.5 and ≤9.5 % * BMI ≤ 45 kg/m2 * Treatment-naive or stable antihyperglycemic therapy with metformin, α-glucosidase-inhibitor and/or SGLT2 inhibitor * Ability to give consent
Exclusion criteria
* Acute infections (hsCRP \> 5mg/dl, body temperature \>37.5°C) * Insulin therapy or treatment with sulfonylureas, glinides, GLP-1 receptor agonists, thiazolidinediones; current treatment with DPP-4 inhibitors or during the 4 weeks prior to baseline examination * Uncontrolled hyperglycemia, e.g. fasting blood glucose \>240 mg/dl * Heart rate \<50 or \>100 beats per minute; systolic blood pressure \<100 or \>160 mmHg; diastolic blood pressure \<50 or \>100 mmHg; uncontrolled hypertension * Creatinine clearance \<60 ml/min (eGFR by MDRD formula) * Severe chronic illnesses, such as congestive heart failure (NYHA III/IV), liver insufficiency (Child-Pugh Class B/C), history of acute coronary syndrome, stroke * Anemia (Hb \<12 g/l for men, Hb \<11 g/l for women) * Participation in another intervention study within 2 months before the examination * Hypersensitivity against AP-325, placebo or other ingredients of IMP * Immunocompromising diseases * Immunomodulatory drugs (e.g. oral cortisone preparations, biologicals) * Thyroid diseases with an unstable metabolic state (change in L-thyroxine dose within the past 6 weeks, TSH and fT4 outside the normal range) * Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method * Past (≤ 5 years) or current history of psychiatric disorders, including psychiatric depression * HIV, hepatitis B or C disease * Previous / current alcohol and / or drug abuse * Malignant cancer * BIA and MR-incompatible metal or magnetic implants, devices or objects inside of or on the body, claustrophobia * Treatment with the following drug groups or agents: Anticoagulant drugs (exception: acetylsalicylic acid 100 mg/day), dihydropyridines (e.g. nifedipine, amlodipine), azilsartan, losartan and irbesartan, celecoxib; if applicable, other drugs that are predominantly metabolized by CYP2C9 * Inhibitors or inducers of CYP2C9, CYP3A4, such as amiodarone, verapamil, rifampicin * Poor CYP2C9 metabolizer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating C-peptide by iAUC of C-peptide during an IVGTT | 4 weeks | Change in circulating C-peptide levels from baseline to end of intervention measured by iAUC of C-peptide during an IVGTT until 60th minute (second phase) with AP-325 compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| iAUC of C-peptide level (overall) | 4 weeks | Change in C-peptide level during an IVGTT from baseline to end of treatment |
| Basal insulin level | 4 weeks | Change in basal insulin level from baseline to end of treatment |
| C-peptide level | 4 weeks | Change in C-peptide level from baseline to end of treatment |
| Glucose level | 4 weeks | Change in glucose level from baseline to end of treatment |
| iAUC of circulating insulin (overall) | 4 weeks | Change in iAUC of circulating insulin during an IVGTT from baseline to end of treatment |
| iAUC of circulating insulin (AIR) (first 10 min) | 4 weeks | Change in iAUC of circulating insulin (AIR) during an IVGTT in the first 10 minutes from baseline to end of treatment |
| iAUC of C-peptide (first 10 min) | 4 weeks | Change in iAUC of C-peptide during an IVGTT in the first 10 minutes from baseline to end of treatment |
| iAUC of glucose (first 10 min) | 4 weeks | Change in iAUC of glucose during an IVGTT in the first 10 minutes from baseline to end of treatment |
| iAUC of glucose level (overall) | 4 weeks | Change in iAUC of glucose level during an IVGTT from baseline to end of treatment |
| peak insulin response | 4 weeks | Change in peak insulin response during an IVGTT from baseline to end of treatment |
| insulin secretion rate (ISR) | 4 weeks | Change in insulin secretion rate (ISR) during an IVGTT from baseline to end of treatment |
| fructosamine levels | 4 weeks | Change in 1.5-Anhydroglucitol glucose from baseline to end of treatment |
| fructosamine levels II | 4 weeks | Change in fructosamine level from baseline to end of treatment |
| fructosamine levels III | 4 weeks | Change in fasting blood glucose from baseline to end of treatment |
| Plasma concentrations of AP-325 | 4 weeks | Change in Plasma concentrations of AP-325 at 1 hour post-dose on Days 1 and 28; pre-dose on Days 4 and 28. Accumulation of Ctrough from Day 4 to Day 28 |
| Ctrough-ss (Day 28) and the change from baseline to Day 28 | 4 weeks | Change in relationship between Ctrough-ss (Day 28) and the change from baseline to Day 28 in primary and secondary endpoints |
| disposition index (DI) | 4 weeks | Change in the disposition index (DI) through Minimal Model during an IVGTT from baseline to end of treatment |
Countries
Germany
Outcome results
None listed