A Study to Investigate the Effect of AZD5004 on Mitiglinide and Pioglitazone in Healthy Participants

An Open-label, Fixed-sequence, Two-part Study to Assess the Effect of AZD5004 on the Pharmacokinetics of Mitiglinide and Pioglitazone in Healthy Participants

The purpose of the study is to assess the effect of AZD5004 on the pharmacokinetics (PK) of mitiglinide and pioglitazone in healthy participants.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD5004; Drug: Mitiglinide; Drug: Pioglitazone

Detailed Description

This is an open-label, fixed-sequence, two-part study of mitiglinide (Part A) and pioglitazone (Part B) in healthy participants. Part A will assess the PK of mitiglinide when administered alone and in combination with AZD5004 while Part B will assess the PK of pioglitazone when administered alone and in combination of AZD5004.

Both parts are independent and non-sequential to each other.

Each study part will comprise of:

1. A screening period of maximum 28 days.
2. Four sequential treatment periods during which the participants will receive the study interventions.
3. A final follow-up visit

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 813-0017
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants with suitable veins for cannulation or repeated venipuncture.
• All females must have a negative serum pregnancy test at the Screening Visit and on admission to the study site.
• Females of childbearing potential must agree to use a highly effective contraception method from enrollment.
• Male Participants, if heterosexually active, must practice true abstinence or use condoms during the trial and their female partners of childbearing potential must use additional effective contraception during the trial.
• Body Mass Index (BMI) between 18 and 35 kg/m² and weigh at least 50 kg.

Exclusion Criteria:

• History of any clinically important disease or disorder which may put the participant at risk or influence the results, including:

  1. Clinically significant inflammatory bowel disease, gastroparesis, severe disease, or surgery affecting the upper gastrointestinal (GI) tract
  2. Cardiovascular disease
  3. Neuromuscular or neurogenic disease
  4. Type 1 or type 2 diabetes mellitus
• History of acute pancreatitis, chronic pancreatitis, gallstones, or elevation in serum lipase/pancreatic amylase.
• History of clinically significant cardiovascular, dermatological, respiratory, neurological, psychiatric or GI disease disorder.
• History of malignant neoplastic disease.
• History or presence of GI disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma.
• Any clinically important abnormalities in clinical chemistry, hematology, coagulation, or urinalysis results.
• Basal calcitonin level ≥ 35 ng/L or history/family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN2).
• Uncontrolled thyroid disease.
• Any positive result on screening for serum human immunodeficiency virus (HIV).
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class to AZD5004, or to mitiglinide and/or pioglitazone.
• Participants who have previously received AZD5004.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Mitiglinide + AZD5004; In Period 1, participants receive a single dose of mitiglinide on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 3-9, then single doses of AZD5004 Dose B once daily from Days 10-16. In Period 2, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose B on Day 17, followed by a single dose of AZD5004 Dose B on Day 18, then single doses of AZD5004 Dose C once daily from Days 19-25, followed by single doses of AZD5004 Dose D once daily from Days 26-32. In Period 3, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose D on Day 33, followed by a single dose of AZD5004 Dose D on Day 34, then single doses of AZD5004 Dose E once daily from Days 35-41. In Period 4, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose E on Day 42, followed by a single dose of AZD5004 Dose E on Day 43.	Drug: AZD5004; AZD5004 will be administered orally.; Drug: Mitiglinide; Mitiglinide will be administered orally.
Experimental: Part B: Pioglitazone + AZD5004; In Period 1, participants receive a single dose of pioglitazone on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 8-14, then single doses of AZD5004 Dose B once daily from Days 15-21. In Period 2, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose B on Day 22, followed by single doses of AZD5004 Dose B once daily from Days 23-28, then single doses of AZD5004 Dose C once daily from Days 29-35, followed by single doses of AZD5004 Dose D once daily from Days 36-42. In Period 3, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose D on Day 43, followed by single doses of AZD5004 Dose D once daily from Days 44-49, then single doses of AZD5004 Dose E once daily from Days 50-56. In Period 4, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose E on Day 57, followed by single doses of AZD5004 Dose E once daily from Days 58-63.	Drug: AZD5004; AZD5004 will be administered orally.; Drug: Pioglitazone; Pioglitazone will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under concentration-time curve from time 0 to infinity (AUCinf)	To assess the effect of AZD5004 on the PK (AUCinf) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To assess the effect of AZD5004 on the PK (AUClast) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
Maximum observed drug concentration (Cmax)	To assess the effect of AZD5004 on the PK (Cmax) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) and AE of special interest (AESI)	To examine the safety and tolerability of AZD5004 alone and in combination with mitiglinide and pioglitazone in healthy participants	Part A: Up to follow-up visit [Day 54 (± 3 days)]; Part B: Up to follow-up visit [Day 74 (± 3 days)]
Terminal elimination half-life (t½λz)	To assess the effect of AZD5004 on the PK (t½λz) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
Terminal rate constant (λz)	To assess the effect of AZD5004 on the PK (λz) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
Time to reach maximum observed concentration (tmax)	To assess the effect of AZD5004 on the PK (tmax) of mitiglinide and pioglitazone in healthy participants	Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on AUCinf (RAUCinf)	To assess the effect of AZD5004 on the PK (RAUCinf) of mitiglinide in healthy participants	From Day 1 to Day 50
Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on AUClast (RAUClast)	To assess the effect of AZD5004 on the PK (RAUClast) of mitiglinide in healthy participants	From Day 1 to Day 50
Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on Cmax (RCmax)	To assess the effect of AZD5004 on the PK (RCmax) of mitiglinide in healthy participants	From Day 1 to Day 50
Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on AUCinf (RAUCinf)	To assess the effect of AZD5004 on the PK (RAUCinf) of pioglitazone in healthy participants	From Day 1 to Day 70
Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on AUClast (RAUClast)	To assess the effect of AZD5004 on the PK (RAUClast) of pioglitazone in healthy participants	From Day 1 to Day 70
Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on Cmax (RCmax)	To assess the effect of AZD5004 on the PK (RCmax) of pioglitazone in healthy participants	From Day 1 to Day 70

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2026
• Primary Completion (Estimated): July 2, 2026
• Study Completion (Estimated): July 2, 2026

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Pharmacokinetics; Type 2 Diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Thiazolidinediones; Pioglitazone; mitiglinide
• Other Study ID Numbers: D7260C00024

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 shared.

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