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

January 9, 2025 updated by: The Deutsche Diabetes Forschungsgesellschaft e.V.

Effects of GABAA Receptor Modulation by AP-325 on Insulin

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
    • NRW
      • Duesseldorf, NRW, Germany, 40225
        • German Diabetes Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AP-325 Treatment
AP-325, film-coated tablet, 50mg once daily
Drug: AP-325
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.
Placebo Comparator: Placebo Treatment
Placebo matching AP-325 film-coated tablet, once daily
Drug: Placebo matching AP-325
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Circulating C-peptide by iAUC of C-peptide during an IVGTT
Time Frame: 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
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Basal insulin level
Time Frame: 4 weeks
Change in basal insulin level from baseline to end of treatment
4 weeks
C-peptide level
Time Frame: 4 weeks
Change in C-peptide level from baseline to end of treatment
4 weeks
Glucose level
Time Frame: 4 weeks
Change in glucose level from baseline to end of treatment
4 weeks
iAUC of circulating insulin (overall)
Time Frame: 4 weeks
Change in iAUC of circulating insulin during an IVGTT from baseline to end of treatment
4 weeks
iAUC of C-peptide level (overall)
Time Frame: 4 weeks
Change in C-peptide level during an IVGTT from baseline to end of treatment
4 weeks
iAUC of glucose level (overall)
Time Frame: 4 weeks
Change in iAUC of glucose level during an IVGTT from baseline to end of treatment
4 weeks
iAUC of circulating insulin (AIR) (first 10 min)
Time Frame: 4 weeks
Change in iAUC of circulating insulin (AIR) during an IVGTT in the first 10 minutes from baseline to end of treatment
4 weeks
iAUC of C-peptide (first 10 min)
Time Frame: 4 weeks
Change in iAUC of C-peptide during an IVGTT in the first 10 minutes from baseline to end of treatment
4 weeks
iAUC of glucose (first 10 min)
Time Frame: 4 weeks
Change in iAUC of glucose during an IVGTT in the first 10 minutes from baseline to end of treatment
4 weeks
disposition index (DI)
Time Frame: 4 weeks
Change in the disposition index (DI) through Minimal Model during an IVGTT from baseline to end of treatment
4 weeks
peak insulin response
Time Frame: 4 weeks
Change in peak insulin response during an IVGTT from baseline to end of treatment
4 weeks
insulin secretion rate (ISR)
Time Frame: 4 weeks
Change in insulin secretion rate (ISR) during an IVGTT from baseline to end of treatment
4 weeks
fructosamine levels
Time Frame: 4 weeks
Change in 1.5-Anhydroglucitol glucose from baseline to end of treatment
4 weeks
fructosamine levels II
Time Frame: 4 weeks
Change in fructosamine level from baseline to end of treatment
4 weeks
fructosamine levels III
Time Frame: 4 weeks
Change in fasting blood glucose from baseline to end of treatment
4 weeks
Plasma concentrations of AP-325
Time Frame: 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
4 weeks
Ctrough-ss (Day 28) and the change from baseline to Day 28
Time Frame: 4 weeks
Change in relationship between Ctrough-ss (Day 28) and the change from baseline to Day 28 in primary and secondary endpoints
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Deutsche Diabetes Forschungsgesellschaft e.V.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Algiax Pharmaceuticals GmbH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Roden, MD, Deutsches Diabetes-Zentrum

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 7, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 17, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 17, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 16, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GAP-325

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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