Diabetes Mellitus, Type 2Phase 2NCT04556760

Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes

A Phase 2 study testing AZD9567 and Prednisolone in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 3 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The study is intended to assess the effect on glycaemic control of AZD9567, as measured by the glucose AUC(0-4) versus baseline following a standardised mixed meal tolerance test (MMTT), compared to prednisolone in adults with type 2 diabetes mellitus (T2DM). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: AZD9567 and Prednisolone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 46 participants
Where: 3 sitesGermany
Study dates: 26 Nov 2020to 9 Jun 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participants with diagnosis of T2DM for 6 months prior to screening: HbA1c in the diabetes range or fasting plasma glucose 126 -220 mg/dL.
On stable metformin therapy for at least 4 weeks, where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred prior to screening and HbA1c 6% - 9.5%, or on dual therapy with metformin in combination with SGLT2i or DPP4i and HbA1c 6% - 8%. Participants on dual therapy will require 2 weeks wash-out of SGLT2i or DPP4i.
Venous access suitable for multiple cannulations
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female participants must be not lactating and not of childbearing potential.
If sexually active, nonsterilized males who have a female partner of childbearing potential must practice effective contraceptive measures.
Capable of giving signed informed consent.
Provision of informed consent prior to any study specific procedures.

Who cannot join

History or presence of type 1 diabetes.
History of severe hypoglycaemia or hypoglycaemia unawareness within the last 6 months.
History or presence of diabetic foot ulcers
Participants with advanced diabetic complications.
History of clinically significant lactic acidosis or ketoacidosis following diagnosis with T2DM.
History of, or known significant infection or positivity at Visit 1, including hepatitis A, B, or C, HIV, tuberculosis that may put the participant at risk during participation in the study.

Show all 27Show fewer

History and / or presence of COVID-19.
Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1.
History of or current alcohol or drug abuse (including marijuana), as judged by the investigator.
Previous psychiatric disorders.
Any latent, acute, or chronic infections or at risk of infection, or history of skin abscesses within 90 days prior to the first administration of investigational medicinal product (IMP) at the discretion of the investigator.
History of adrenal insufficiency.
History or current inflammatory disorder.
Any other condition that, in the opinion of the investigator, would interfere with evaluations of the IMP or interpretation of participant safety or study results.
History of severe allergy/hypersensitivity to AZD9567 or any of the excipients of the product, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
Oral or parenteral steroids 8 weeks prior to randomisation and during the study. Topical and inhaled steroids 4 weeks prior to randomisation are acceptable.
Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to.
Receipt of live or live attenuated vaccine within 4 weeks prior to the first administration of IMP.
Planned in-patient surgery, major dental procedure, or hospitalisation during the study.
Previous participation or participation in any other research study within 1 month prior to Visit 1.
Patient treated with any investigational drug within 30 days (or 5 half-lives, whichever is longer) prior to Visit 1.
Uncontrolled hypertension (BP > 160 mmHg systolic or > 95 mmHg diastolic).
Diagnosis of heart failure and current symptoms regardless of definition, ie, HfpEF, HfrEF.
Acute coronary syndrome / unstable angina, coronary intervention procedures (percutaneous coronary intervention or coronary artery bypass graft) within the past 6 months.
Stroke within the past 3 months.
QTcF > 470 ms or family history of long QT-syndrome.
AV-block II-III or sinus node dysfunction with significant pause, not treated with pacemaker.

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

Research Site
Mainz, 55116
Research Site
Mannheim, 68167
Research Site
Neuss, 41460

Other trials in Germany

About this study

Official title: A Phase 2a Randomised, Double Blind, Multi-centre Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes

Read the detailed description

This is a randomised, double blind, multi-centre, double dummy, and two-way cross-over study.

There will be a total of three cohorts. Each cohort will be treated for two 72-hour periods in a cross-over design, with a 3-week washout period between treatment periods. The total length of participant engagement (from screening to follow-up) is 79 days.

Conditions: Diabetes Mellitus, Type 2
Being tested: AZD9567, Prednisolone, Placebo
Keywords: Type 2 Diabetes Mellitus, Glucose Homeostasis, Pharmacodynamic, AZD9567, Prednisolone
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD9567Drug
Participants will receive 72 mg/day (oral suspension) of AZD9567 for 3 consecutive days of each treatment period in Cohort 1 and 40 mg/day for 3 consecutive days of each treatment period in Cohort 2.
PrednisoloneDrug
Participants will receive 40 mg/day of prednisolone for 3 consecutive days of each treatment period in Cohort 1, 20 mg/day of prednisolone for 3 consecutive days of each treatment period in Cohort 2, and 5 mg/day prednisolone for 3 consecutive days of each treatment period in Cohort 3.
PlaceboOther
Participants will receive placebo for 3 consecutive days of each treatment period in Cohort 3.

Study groups in NCT04556760
Study group	Role	What they receive
Cohort 1	Experimental	Participants will be randomised in a ratio of 1:1 to receive AZD9567 and prednisolone over two 72 hour periods in a cross over design (72 mg AZD9567 followed by 40 mg prednisolone [AB sequence group] or 40 mg prednisolone followed by 72 mg AZD9567 [BA sequence group]). Receives: Drug: AZD9567; Drug: Prednisolone
Cohort 2	Experimental	Participants will be randomised in a ratio of 1:1 to receive AZD9567 and prednisolone over two 72 hour periods in a cross over design (40 mg AZD9567 followed by 20 mg prednisolone [AB sequence group] or 20 mg prednisolone followed by 40 mg AZD9567 [BA sequence group]). Receives: Drug: AZD9567; Drug: Prednisolone
Cohort 3	Active comparator	Participants will be randomised in a ratio of 1:1 to receive placebo and prednisolone over two 72 hour periods in a cross over design (placebo followed by 5 mg prednisolone [AB sequence group] or 5 mg prednisolone followed by placebo [BA sequence group]). Receives: Drug: Prednisolone; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4)
The change from baseline in glucose AUC(0-4) was analysed to determine the Pharmacodynamic (PD) effect of AZD9567 compared to Prednisolone following a standardised Mixed meal tolerance test (MMTT).
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Days -1 (baseline), and Days 4 (Treatment period 1 and 2)

Secondary outcomes (27)

Mean Glucose Level as Determined Via the Continuous Glucose Monitoring (CGM) System
The mean glucose levels in mmol/L at 48-72 h was analysed to determine the effect of AZD9567 on CGM compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: 48 to 72 hours
Rise in Mean Glucose Levels Over 24-hour Periods From Start of IMP Dosing
The mean glucose level in mmol/L was analysed to determine the effect of AZD9567 on CGM compared to prednisolone.
For the calculation of the rise in mean glucose levels, the baseline was the average of the values from -24 hours to first dosing on Day 1 of each period.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: Baseline and up to 72 hours (Treatment period 1 and 2)
Change From Baseline in Fasting Glucose
Pharmacodynamic effects (fasting glucose) of AZD9567 following a MMTT were evaluated as compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Insulin)
Effects of AZD9567 on insulin AUC(0-4) were assessed following MMTT compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucagon)
Effects of AZD9567 on glucagon AUC(0-4) were assessed following MMTT in comparison to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucagon-like Peptide-1 [GLP-1])
Effects of AZD9567 on GLP-1 AUC(0-4) were assessed following MMTT in comparison to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucose-dependent Insulin Releasing Polypeptide [GIP])
Effects of AZD9567 on GIP AUC(0-4) were assessed following MMTT in comparison to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in AUC(0-4) on C-peptide
Effects of AZD9567 on C-peptide AUC(0-4) were assessed through a MMTT in comparison to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of Insulin to Glucose Level Between 10 and 0 Minutes (ΔI10/ΔG10)
Effects of AZD9567 on ΔI10/ΔG10 of beta cell function from the MMTT compared to Prednisolone was evaluated.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of Insulin to Glucose Level Between 30 and 0 Minutes [ΔI30/ΔG30])
Effects of AZD9567 on ΔI30/ΔG30 of beta cell function from the MMTT compared to Prednisolone was evaluated.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of C-peptide to Glucose Level Between 10 and 0 Minutes (ΔC10/ΔG10)
Effects of AZD9567 on ΔC10/ΔG10 of beta cell function from the MMTT compared to Prednisolone was evaluated.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of C-peptide to Glucose Level Between 30 and 0 Minutes (ΔC30/ΔG30)
Effects of AZD9567 on ΔC30/ΔG30 of beta cell function from the MMTT compared to Prednisolone was evaluated.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in 24-hour Urinary Potassium Excretion
The concentration of potassium in urine was measured over 24 hours to determine the effect of AZD9567 on urinary potassium (U-K) excretion compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in 24-hour Urinary Sodium Excretion
The concentration of sodium in urine was measured over 24 hours to determine the effect of AZD9567 on urinary-sodium (U-Na) excretion compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Concentration (AUClast)
AUClast of AZD9567 following once daily dosing was evaluated.
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours Post-dose [AUC(0-24)]
AUC(0-24) of AZD9567 following once daily dosing was evaluated.
Measured: 24 hours post dose
Area Under the Plasma Concentration Versus Time Curve From Zero to 6 Hours Post-dose [AUC(0-6)]
AUC(0-6) of AZD9567 following once daily dosing was evaluated.
Measured: 6 hours post dose
Maximum Observed Drug Concentration (Cmax)
Cmax of AZD9567 following once daily dosing was evaluated.
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Time to Reach Maximum Observed Drug Concentration (Tmax)
Tmax of AZD9567 following once daily dosing was evaluated.
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Terminal Elimination Half-life (t½λz)
t½λz of AZD9567 following once daily dosing was evaluated.
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Apparent Total Body Clearance of Drug From Plasma After Extravascular (CL/F)
CL/F of AZD9567 following once daily dosing was evaluated.
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Apparent Volume of Distribution Following Extravascular Administration (Vz/F)
Vz/F of AZD9567 was derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).
Measured: Upto 30 hours post dose (Treatment period 1 and 2)
Tumour Necrosis Factor Alpha (TNFα) Concentrations
Relationship between AZD9567 exposure and inhibition of LPS-stimulated TNFα release for high and low dose comparison (Cohort 1 and Cohort 2) was assessed. LPS-stimulated TNFα concentration was measured.
Measured: On Days 3 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Free Fatty Acids)
Effects of AZD9567 on free fatty acids were evaluated following a MMTT compared to prednisolone.
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Homeostatic Model Assessment- Insulin Resistance (HOMA-IR)
The HOMA-IR was calculated based on glucose and insulin measured prior to MMTT.
HOMA-IR= Glucose(mmol/L) x Insulin (mU/L) / 22.5
HOMA-IR score estimates the degree of insulin resistance. Higher range indicates greater insulin resistance (i.e. high diabetes risk), while lower range indicates insulin sensitivity (i.e. low diabetes risk)
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in HOMA-insulin Sensitivity (HOMA-S)
Insulin sensitivity is a term used to indicate the responsiveness of the peripheral tissue cells to insulin, and their resultant capacity to uptake glucose out of the bloodstream.
HOMA-S score estimates the degree of insulin sensitivity. HOMA-S was calculated as the reciprocal of HOMA-IR.
Higher values indicates greater insulin sensitivity (i.e. low diabetes risk), while lower values indicates insulin resistance (i.e. high diabetes risk)
In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0.
In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.
Measured: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Number of Participants With Adverse Events
Safety and tolerability of AZD9567 was assessed.
Measured: From screening up to 79 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Nov 20209 Jun 2021

First posted21 Sep 2020
Study start26 Nov 2020
Primary completion9 Jun 2021
Study completion9 Jun 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
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: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04556760
Sponsor's protocol ID: D6470C00005
Status last verified: Feb 2024
First submitted: 15 Sep 2020
Last updated: 18 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2a Randomised, Double Blind, Multi-centre Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes
ClinicalTrials.gov ID: NCT04556760
Acronym / sponsor ID: D6470C00005
Conditions: Diabetes Mellitus, Type 2
Keywords: Type 2 Diabetes Mellitus, Glucose Homeostasis, Pharmacodynamic, AZD9567, Prednisolone
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 26 Nov 2020 (actual)
Primary completion: 9 Jun 2021 (actual)
Study completion: 9 Jun 2021 (actual)
First posted: 21 Sep 2020 (actual)
Results: Posted 18 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This is a randomised, double blind, multi-centre, double dummy, and two-way cross-over study.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Experimental	Drug: AZD9567, Drug: PrednisoloneParticipants will be randomised in a ratio of 1:1 to receive AZD9567 and prednisolone over two 72 hour periods in a cross over design (72 mg AZD9567 followed by 40 mg prednisolone [AB sequence group] or 40 mg prednisolone followed by 72 mg AZD9567 [BA sequence group]).
Cohort 2	Experimental	Drug: AZD9567, Drug: PrednisoloneParticipants will be randomised in a ratio of 1:1 to receive AZD9567 and prednisolone over two 72 hour periods in a cross over design (40 mg AZD9567 followed by 20 mg prednisolone [AB sequence group] or 20 mg prednisolone followed by 40 mg AZD9567 [BA sequence group]).
Cohort 3	Active comparator	Drug: Prednisolone, Other: PlaceboParticipants will be randomised in a ratio of 1:1 to receive placebo and prednisolone over two 72 hour periods in a cross over design (placebo followed by 5 mg prednisolone [AB sequence group] or 5 mg prednisolone followed by placebo [BA sequence group]).

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Participants with diagnosis of T2DM for 6 months prior to screening: HbA1c in the diabetes range or fasting plasma glucose 126 -220 mg/dL.
On stable metformin therapy for at least 4 weeks, where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred prior to screening and HbA1c 6% - 9.5%, or on dual therapy with metformin in combination with SGLT2i or DPP4i and HbA1c 6% - 8%. Participants on dual therapy will require 2 weeks wash-out of SGLT2i or DPP4i.
Venous access suitable for multiple cannulations
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female participants must be not lactating and not of childbearing potential.

Key exclusion criteria (27 listed)

History or presence of type 1 diabetes.
History of severe hypoglycaemia or hypoglycaemia unawareness within the last 6 months.
History or presence of diabetic foot ulcers
Participants with advanced diabetic complications.
History of clinically significant lactic acidosis or ketoacidosis following diagnosis with T2DM.

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
AZD9567Participants will receive 72 mg/day (oral suspension) of AZD9567 for 3 consecutive days of each treatment period in Cohort 1 and 40 mg/day for 3 consecutive days of each treatment period in Cohort 2.	Drug	Cohort 1, Cohort 2
PrednisoloneParticipants will receive 40 mg/day of prednisolone for 3 consecutive days of each treatment period in Cohort 1, 20 mg/day of prednisolone for 3 consecutive days of each treatment period in Cohort 2, and 5 mg/day prednisolone for 3 consecutive days of each treatment period in Cohort 3.	Drug	Cohort 1, Cohort 2, Cohort 3
PlaceboParticipants will receive placebo for 3 consecutive days of each treatment period in Cohort 3.	Other	Cohort 3

Primary outcome

Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4)
Time frame: On Days -1 (baseline), and Days 4 (Treatment period 1 and 2)
The change from baseline in glucose AUC(0-4) was analysed to determine the Pharmacodynamic (PD) effect of AZD9567 compared to Prednisolone following a standardised Mixed meal tolerance test (MMTT). In Cohort 1 and 2, Placebo was not administered, therefore in Placebo row the participants analyzed is kept as 0. In Cohort 3, AZD9567 was not administered, therefore in AZD9567 row the participants analyzed is kept 0.

27 secondary outcomes

Mean Glucose Level as Determined Via the Continuous Glucose Monitoring (CGM) System
Time frame: 48 to 72 hours
Rise in Mean Glucose Levels Over 24-hour Periods From Start of IMP Dosing
Time frame: Baseline and up to 72 hours (Treatment period 1 and 2)
Change From Baseline in Fasting Glucose
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Insulin)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucagon)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucagon-like Peptide-1 [GLP-1])
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Glucose-dependent Insulin Releasing Polypeptide [GIP])
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in AUC(0-4) on C-peptide
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of Insulin to Glucose Level Between 10 and 0 Minutes (ΔI10/ΔG10)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of Insulin to Glucose Level Between 30 and 0 Minutes [ΔI30/ΔG30])
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of C-peptide to Glucose Level Between 10 and 0 Minutes (ΔC10/ΔG10)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Ratio of C-peptide to Glucose Level Between 30 and 0 Minutes (ΔC30/ΔG30)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in 24-hour Urinary Potassium Excretion
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in 24-hour Urinary Sodium Excretion
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Concentration (AUClast)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours Post-dose [AUC(0-24)]
Time frame: 24 hours post dose
Area Under the Plasma Concentration Versus Time Curve From Zero to 6 Hours Post-dose [AUC(0-6)]
Time frame: 6 hours post dose
Maximum Observed Drug Concentration (Cmax)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Time to Reach Maximum Observed Drug Concentration (Tmax)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Terminal Elimination Half-life (t½λz)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Apparent Total Body Clearance of Drug From Plasma After Extravascular (CL/F)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Apparent Volume of Distribution Following Extravascular Administration (Vz/F)
Time frame: Upto 30 hours post dose (Treatment period 1 and 2)
Tumour Necrosis Factor Alpha (TNFα) Concentrations
Time frame: On Days 3 (Treatment period 1 and 2)
Change From Baseline AUC(0-4) on Hormones Related to Glucose Homeostasis (Free Fatty Acids)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in Homeostatic Model Assessment- Insulin Resistance (HOMA-IR)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Change From Baseline in HOMA-insulin Sensitivity (HOMA-S)
Time frame: On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)
Number of Participants With Adverse Events
Time frame: From screening up to 79 days

Results and safety

Results posted to the registry on 18 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: 72 mg AZD9567 First, Then 40 mg Prednisolone	14	14
Cohort 1:40 mg Prednisolone First, Then 72 mg AZD9567	14	13
Cohort 2: 40 mg AZD9567 First, Then 20 mg Prednisolone	5	5
Cohort 2: 20mg Prednisolone First, Then 40 mg AZD9567	4	3
Cohort 3: Placebo First, Then 5 mg Prednisolone	4	4
Cohort 3: 5 mg Prednisolone First, Then Placebo	5	5

Primary outcome: Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4)

Time frame: On Days -1 (baseline), and Days 4 (Treatment period 1 and 2). Least squares mean (Standard Error). Unit: minute*millimole/liter (min*mmol/L)

Measure	Cohort 1 n = 27	Cohort 2 n = 8	Cohort 3 n = 9
AZD9567	-190.0296 (63.8805)	-182.7172 (149.8600)	–
Prednisolone	-57.0768 (63.8762)	-40.6842 (141.7154)	-184.9677 (88.9807)
Placebo	–	–	-311.8506 (88.5443)

Cohort 1: Mean Difference (Final Values): -132.9528 (95% CI -256.5082 to -9.3973), p = 0.036, Mixed Models Analysis
Cohort 2: Mean Difference (Final Values): -142.0330 (95% CI -554.8722 to 270.8061), p = 0.432, Mixed Models Analysis
Cohort 3: Mean Difference (Final Values): -126.8829 (95% CI -236.0426 to -17.7233), p = 0.030, Mixed Models Analysis

Population analysed: Full Analysis Set (FAS) consisted of all randomised patients who received at least 1 dose of study treatment.

27 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Screening up to Final/ end of treatment visit (Day 79).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: AZD9567 72mg	0 of 27 (0%)	4 of 27 (14.8%)	0 of 27
Cohort 1: Prednisolone 40mg	0 of 27 (0%)	7 of 27 (25.9%)	0 of 27
Cohort 2: AZD9567 40mg	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Cohort 2: Prednisolone 20mg	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Cohort 3: Placebo	0 of 9 (0%)	1 of 9 (11.1%)	0 of 9
Cohort 3: Prednisolone 5mg	0 of 9 (0%)	0 of 9 (0%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Statistical Analysis Plan (SAP)Link provided by the sponsor.
ProtocolLink provided by the sponsor.
CSR SynopsisLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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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.

Tim Heise principal investigator

Profil Institut fur Stoffwechselforschung GmbH

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD9567 and Prednisolone in people with Diabetes Mellitus, Type 2, run by AstraZeneca at 3 sites 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 8 inclusion and 27 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 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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. 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?

Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change From Baseline in Glucose Area Under the Plasma Concentration Versus Time Curve From Zero to 4 Hours Post-dose AUC(0-4) (time frame: On Days -1 (baseline), and Days 4 (Treatment period 1 and 2)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04556760.

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 18 Jul 2024.