A Study to Investigate Multiple Ascending Doses of AZD5004 in Healthy Japanese Participants and Participants With Type 2 Diabetes Mellitus

A Phase I, Randomised, Single-blind, Placebo-controlled, Single and Repeated Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5004 in Healthy Japanese Participants and With Type 2 Diabetes Mellitus

This Phase I study will gather important information on the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5004 in both healthy Japanese participants and Japanese participants with T2DM.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Healthy Participants
• Intervention / Treatment: Drug: AZD5004(Part A); Drug: Placebo(Part A); Drug: AZD5004(Part B); Drug: Placebo(Part B)

Detailed Description

This is a placebo-controlled study to assess the safety, efficacy, tolerability, and PK of single and repeated dosing of AZD5004 compared with placebo.

Participants who are eligible according to the inclusion/exclusion criteria will be randomized to receive AZD5004 or matching placebo.

The study will comprise:

1. A Screening Period of maximum 28 days.
2. A Treatment Period of 1 day(Part A) or 105 days (Part B).
3. A final Follow-up Visit approximately 7 days(Part A) or 14 days(Part B) after the last study intervention administration.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka-shi, Japan, 532-0003
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Japanese men or women, and 18-65 years of age inclusive, at the time of signing the informed consent.

Inclusion Criteria for Part A:

• HbA1c ≤ 6.0%.
• Body weight ≥ 50.0 kg and BMI within the range 18.0-32.0 kg/m2.

Inclusion Criteria for Part B:

• HbA1c ≥ 6.5% and ≤ 10.5%.
• Not on any other diabetic medications.
• Body weight ≥ 60.0 kg and BMI within the range 24.0-35.0 kg/m2

Exclusion Criteria:

• Has a clinically relevant acute or chronic medical condition or disease.
• History of acute pancreatitis and chronic pancreatitis, gallstones.
• Abnormal renal function.
• Known clinically significant gastric emptying abnormality
• Significant hepatic disease.
• Uncontrolled thyroid disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A-AZD5004; Participants will receive AZD5004 orally.	Drug: AZD5004(Part A); Single dose of AZD5004 oral on Day1
Placebo Comparator: Part A-Placebo; Participants will receive matching Placebo orally.	Drug: Placebo(Part A); Single dose of placebo oral on Day1
Experimental: Part B-AZD5004; Participants will receive AZD5004 orally.	Drug: AZD5004(Part B); AZD5004 will be administered as an oral tablet once daily.
Placebo Comparator: Part B-Placebo; Participants will receive matching Placebo orally.	Drug: Placebo(Part B); Placebo will be administered as an oral tablet once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To assess the safety and tolerability of AZD5004 following single oral doses in healthy participants.	From screening (Day -28) to last follow up visit (Day 8)
PartB: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To assess the safety and tolerability of AZD5004 following multiple oral ascending doses in participants with T2DM.	From screening (Day -28) to last follow up visit (Day 119 )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PartB: AUC0-4 for glucose, insulin and C-peptide for MMTT	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 105
PartB: Absolute change from baseline to Day 105 in fasting plasma glucose	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 105
PartB: % change from baseline to Day 105 in HOMA-IR	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 105
PartB: The proportion of time in hyperglycaemia /hypoglycaemia over the last 7-day intervals at each dose level in CGM	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 106
PartB: % change from baseline to Day 105 in body weight (kg)	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 105
PartB: % change from baseline to Day 105 in waist circumference (cm)	To describe the PD of AZD5004 following repeated daily administration in participants with T2DM in MAD	From Day 1 to Day 105
PartA: Area under the Plasma Concentration vs. Time Curve(AUC0-24)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Area under the Plasma Concentration vs. Time Curve from Zero until the Time of the Last Concentration above the Limit of Quantification(AUC0-tlast)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Area under the Plasma Concentration vs. Time Curve from Zero to Infinity(AUC0-inf)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Maximum Observed Plasma Concentration(Cmax)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Plasma Concentration at 24 Hours Post-Dose(C24h)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Time of Occurrence of Maximum Plasma Concentration(tmax)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Half-Life(t1/2)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Last measurable Non-Zero Concentration(Clast)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Last measurable Non-Zero ConcentrationTime to Last Detectable Concentration(tlast)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Apparent Oral Clearance(CL/F)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Cumulative Urinary Excretion(Ae)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartA: Clearance(CLR)	To describe the PK (plasma and urine) of AZD5004 following a single administration in healthy participants in SAD	From Day 1 to Day 6
PartB: Area under the Plasma Concentration vs. Time Curve(AUC0-24)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 1
PartB: Maximum Observed Plasma Concentration(Cmax)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 1, Day 49, Day 63, Day 77, Day91, Day105
PartB: Plasma Concentration at 24 Hours Post-Dose(C24h)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 1
PartB: Time of Occurrence of Maximum Plasma Concentration(tmax)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 1, Day 49, Day 63, Day 77, Day91, Day105
PartB: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 1
PartB: Area under the Plasma Concentration vs. Time Curve over the Dosing Interval(AUC0-τ)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Observed Concentration at the End of the Dosing Interval(Cτ)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Half-Life(t1/2)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Apparent Oral Clearance(CL/F)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 49, Day 63, Day 77, Day 91, Day 105
PartB: Cumulative Urinary Excretion(Ae)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 105
PartB: Clearance(CLR)	To describe the PK (plasma and urine) of AZD5004 following repeated daily administration in participants with T2DM in MAD	Day 105

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2024
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: November 21, 2024
• First Posted (Actual): November 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Type 2 Diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: D7260C00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests 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 approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No