Effects of GABAA Receptor Modulation by AP-325 on Insulin Secretion in Patients With Type 2 Diabetes

• Status: Not yet recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Deutsche Diabetes Forschungsgesellschaft e.V.
• Collaborator: komIT - Center of Competence for Innovative Diabetes Therapy

Criteria

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