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

The Deutsche Diabetes Forschungsgesellschaft e.V.

Status and phase: Completed; Phase 2

Conditions: Type2 Diabetes

Treatments: Drug: Placebo matching AP-325; Drug: AP-325

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05160272

GAP-325

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 25 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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38 participants in 2 patient groups, including a placebo group

AP-325 Treatment

Experimental group

Description:

AP-325, film-coated tablet, 50mg once daily

Treatment:

Drug: AP-325

Placebo Treatment

Placebo Comparator group

Description:

Placebo matching AP-325 film-coated tablet, once daily

Treatment:

Drug: Placebo matching AP-325