Type2 DiabetesPhase 2NCT05160272
Effects of GABAA Receptor Modulation by AP-325 on Insulin Secretion in Patients with Type 2 Diabetes
A Phase 2 study testing AP-325 in people with Type2 Diabetes, run by The Deutsche Diabetes Forschungsgesellschaft e.V. at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Type2 Diabetes
- What is being tested?
- AP-325
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteGermany
- Study dates
- 7 Jan 2022to 17 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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 locations and contacts
1 site in 1 country.
Germany1 site
German Diabetes Center
Düsseldorf, North Rhine-Westphalia, 40225
About this study
Official title: 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.
- Conditions
- Type2 Diabetes
- Being tested
- AP-325, Placebo matching AP-325
- Keywords
- Type 2 Diabetes, Diabetes mellitus, GABAA receptor, β-cell function, glycemic control
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP-325Drug
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.
Placebo matching AP-325Drug
Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment.
| Study group | Role | What they receive |
|---|---|---|
| AP-325 Treatment | Experimental | AP-325, film-coated tablet, 50mg once daily Receives: Drug: AP-325 |
| Placebo Treatment | Placebo comparator | Placebo matching AP-325 film-coated tablet, once daily Receives: Drug: Placebo matching AP-325 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating C-peptide by iAUC of C-peptide during an IVGTT
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
Measured: 4 weeks
Secondary outcomes (17)
Basal insulin level
Change in basal insulin level from baseline to end of treatment
Measured: 4 weeks
C-peptide level
Change in C-peptide level from baseline to end of treatment
Measured: 4 weeks
Glucose level
Change in glucose level from baseline to end of treatment
Measured: 4 weeks
iAUC of circulating insulin (overall)
Change in iAUC of circulating insulin during an IVGTT from baseline to end of treatment
Measured: 4 weeks
iAUC of C-peptide level (overall)
Change in C-peptide level during an IVGTT from baseline to end of treatment
Measured: 4 weeks
iAUC of glucose level (overall)
Change in iAUC of glucose level during an IVGTT from baseline to end of treatment
Measured: 4 weeks
iAUC of circulating insulin (AIR) (first 10 min)
Change in iAUC of circulating insulin (AIR) during an IVGTT in the first 10 minutes from baseline to end of treatment
Measured: 4 weeks
iAUC of C-peptide (first 10 min)
Change in iAUC of C-peptide during an IVGTT in the first 10 minutes from baseline to end of treatment
Measured: 4 weeks
iAUC of glucose (first 10 min)
Change in iAUC of glucose during an IVGTT in the first 10 minutes from baseline to end of treatment
Measured: 4 weeks
disposition index (DI)
Change in the disposition index (DI) through Minimal Model during an IVGTT from baseline to end of treatment
Measured: 4 weeks
peak insulin response
Change in peak insulin response during an IVGTT from baseline to end of treatment
Measured: 4 weeks
insulin secretion rate (ISR)
Change in insulin secretion rate (ISR) during an IVGTT from baseline to end of treatment
Measured: 4 weeks
fructosamine levels
Change in 1.5-Anhydroglucitol glucose from baseline to end of treatment
Measured: 4 weeks
fructosamine levels II
Change in fructosamine level from baseline to end of treatment
Measured: 4 weeks
fructosamine levels III
Change in fasting blood glucose from baseline to end of treatment
Measured: 4 weeks
Plasma concentrations of AP-325
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
Measured: 4 weeks
Ctrough-ss (Day 28) and the change from baseline to Day 28
Change in relationship between Ctrough-ss (Day 28) and the change from baseline to Day 28 in primary and secondary endpoints
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2021
- Study start7 Jan 2022
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Deutsche Diabetes Forschungsgesellschaft e.V.
- Sponsor type
- University, hospital or other
- Collaborators
- Algiax Pharmaceuticals GmbH
- Responsible party
- Sponsor
- Investigators
- Michael Roden, MD, Principal investigator, Deutsches Diabetes-Zentrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05160272
- Sponsor's protocol ID
- GAP-325
- Status last verified
- Dec 2024
- First submitted
- 17 Nov 2021
- Last updated
- 10 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of GABAA Receptor Modulation by AP-325 on Insulin
- ClinicalTrials.gov ID
- NCT05160272
- Acronym / sponsor ID
- GAP-325
- Conditions
- Type2 Diabetes
- Keywords
- Type 2 Diabetes, Diabetes mellitus, GABAA receptor, β-cell function, glycemic control
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- The Deutsche Diabetes Forschungsgesellschaft e.V.University, hospital or other
- Collaborators
- Algiax Pharmaceuticals GmbH
- Study start
- 7 Jan 2022 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 16 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AP-325 Treatment | Experimental | Drug: AP-325AP-325, film-coated tablet, 50mg once daily |
| Placebo Treatment | Placebo comparator | Drug: Placebo matching AP-325Placebo matching AP-325 film-coated tablet, once daily |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (22 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AP-325Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment. | Drug | AP-325 Treatment |
| Placebo matching AP-325Measurement of the effect of AP-325 50mg/d compared to matching placebo after 4-week treatment. | Drug | Placebo Treatment |
Primary outcome
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
17 secondary outcomes
Basal insulin level
Time frame: 4 weeks
C-peptide level
Time frame: 4 weeks
Glucose level
Time frame: 4 weeks
iAUC of circulating insulin (overall)
Time frame: 4 weeks
iAUC of C-peptide level (overall)
Time frame: 4 weeks
iAUC of glucose level (overall)
Time frame: 4 weeks
iAUC of circulating insulin (AIR) (first 10 min)
Time frame: 4 weeks
iAUC of C-peptide (first 10 min)
Time frame: 4 weeks
iAUC of glucose (first 10 min)
Time frame: 4 weeks
disposition index (DI)
Time frame: 4 weeks
peak insulin response
Time frame: 4 weeks
insulin secretion rate (ISR)
Time frame: 4 weeks
fructosamine levels
Time frame: 4 weeks
fructosamine levels II
Time frame: 4 weeks
fructosamine levels III
Time frame: 4 weeks
Plasma concentrations of AP-325
Time frame: 4 weeks
Ctrough-ss (Day 28) and the change from baseline to Day 28
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Roden, MD principal investigator
Deutsches Diabetes-Zentrum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AP-325 in people with Type2 Diabetes, run by The Deutsche Diabetes Forschungsgesellschaft e.V. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Circulating C-peptide by iAUC of C-peptide during an IVGTT (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2025.