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

NCT04556760 | Completed Phase 2 Results

• 1 other identifier: D6470C00005
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief 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). The study will also evaluate the safety, tolerability, and pharmacokinetics (PK) of AZD9567.

Conditions

Diabetes Mellitus, Type 2

Keywords

Type 2 Diabetes Mellitus; Glucose Homeostasis; Pharmacodynamic; AZD9567; Prednisolone

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  48 to 72 hours

• Rise in Mean Glucose Levels Over 24-hour Periods From Start of IMP Dosing

  Baseline and up to 72 hours (Treatment period 1 and 2)

• Change From Baseline in Fasting Glucose

  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)

  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)

  On Day -1 (Baseline), and Day 4 (Treatment period 1 and 2)

Study Arms (3)

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 \[BA sequence group\]).

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 \[BA sequence group\]).

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 \[BA sequence group\]).

Drug: Prednisolone; Other: Placebo

Interventions

AZD9567 DRUG

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.

Cohort 1; Cohort 2

Prednisolone DRUG

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.

Cohort 1; Cohort 2; Cohort 3

Placebo OTHER

Participants will receive placebo for 3 consecutive days of each treatment period in Cohort 3.

Cohort 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (3)

Research Site

Mainz, 55116, Germany

Location

Research Site

Mannheim, 68167, Germany

Location

Research Site

Neuss, 41460, Germany

Location

Related Links

• Statistical Analysis Plan (SAP)
• Protocol
• CSR Synopsis

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

AZD9567; Prednisolone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-94 79

Study Officials

• Tim Heise

  Profil Institut fur Stoffwechselforschung GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both participants and investigators will be blinded. Investigators will remain blinded to each participant's assigned study intervention throughout the course of the study. In order to maintain this blind, a third party will be responsible for the reconstitution and dispensation of all study interventions.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 21, 2020
• Study Start: November 26, 2020
• Primary Completion: June 9, 2021
• Study Completion: June 9, 2021
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DE (3)