A Study to Investigate Multiple Ascending Doses and Relative Bioavailability of AZD5004 in Healthy Participants

A Phase I, Two-Part Study in Healthy Volunteers Consisting of a Randomized, Single-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD5004 and a Randomized, Open-Label, Two-way Cross-over Study to Compare the Relative Bioavailability of Two Oral Tablet Strengths of AZD5004

The main purpose of this study is to assess the safety, tolerability, and pharmacokinetic (PK) of AZD5004 administered as multiple oral doses in healthy participants and to compare the relative bioavailability of two oral tablet strengths of AZD5004.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Placebo; Drug: AZD5004

Detailed Description

This study comprises of 2 parts - Part A and Part B.

Part A is a placebo-controlled study to assess the safety, efficacy, tolerability, and PK of 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.

Part A will comprise:

1. A Screening Period of maximum 28 days.
2. A Treatment Period of 106 days.
3. A final Follow-up Visit approximately 14 days after the last study intervention administration.

Part B is a two-way cross-over study to compare the relative bioavailability of 2 oral tablet strengths of Formulation 1 (F1) of AZD5004.

The purpose of this study is to expand product knowledge between the 2 oral tablet strengths on plasma exposure levels to guide Phase 3 drug product development. The participants will be split into 2 groups. Group 1 will be dosed with Treatment 1 of AZD5004 and then dosed with Treatment 2 of AZD5004. Group 2 will be dosed with Treatment 2 of AZD5004 and then dosed with Treatment 1 of AZD5004.

Part B of the study will comprise:

1. A Screening Period of maximum 28 days.
2. Two Treatment Periods, each consisting of 7 days.
3. A final Follow-up Visit approximately 6 days after the last dose of study intervention administration.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Must have suitable veins for cannulation or repeated venipuncture.
• Female(s) of Childbearing Potential must use adequate contraception (oral contraceptives are not permitted).
• Have a BMI ≥ 23 kg/m2 and not exceeding 35 kg/m2 inclusive and weigh at least 60 kg.
• No or off statin treatment for ≥ 4 weeks prior to the study treatment.

Exclusion Criteria:

• History of any clinically important disease or disorder.
• History of acute pancreatitis, chronic pancreatitis, gallstones, or elevation in serum lipase/pancreatic amylase.
• History or presence of gastrointestinal, hepatic, or renal disease.
• Clinically significant hepatic disease, inflammatory bowel disease, gastroparesis, severe disease, or surgery affecting the upper gastrointestinal tract.
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
• Any clinically important abnormalities in rhythm, blood pressure, heart rate, conduction or morphology of the resting electrocardiogram (ECG).
• Uncontrolled thyroid disease, defined as thyroid-stimulating hormone > 6.0 mIU/L or < 0.4 mIU/L at Screening.
• Current smokers or known history of alcohol or drug abuse.
• History of severe allergy/hypersensitivity or excessive intake of caffeine-containing drinks or food.
• Use of any prescribed or nonprescribed medication including antacids or analgesics.
• Participants who are on or are planning to undertake a weight loss program.
• History of psychosis, major depressive disorder, suicide attempt or suicidal ideation within the past year.
• Lactating, breastfeeding, or pregnant females or females who intend to become pregnant.
• Participants who are vegans or have medical dietary restrictions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Multiple Ascending dose (MAD) (AZD5004); Participants will receive repeated dosing of AZD5004 orally.	Drug: AZD5004; Participants will receive oral tablets of AZD5004 in Part A and Part B of the study as per arms they are assigned.; Other Names: ECC5004
Placebo Comparator: Part A: Placebo; Participants will receive matching Placebo orally.	Drug: Placebo; Placebo will be administered as an oral tablet once daily.
Experimental: Part B: Treatment 1 (AZD5004); Participants in Group 1 will receive Treatment 1 of AZD5004 and then Treatment 2 of AZD5004. Participants in Group 2 will receive Treatment 2 of AZD5004 and then Treatment 1 of AZD5004.	Drug: AZD5004; Participants will receive oral tablets of AZD5004 in Part A and Part B of the study as per arms they are assigned.; Other Names: ECC5004
Experimental: Part B: Treatment 2 (AZD5004); Participants in Group 1 will receive Treatment 1 of AZD5004 and then Treatment 2 of AZD5004. Participants in Group 2 will receive Treatment 2 of AZD5004 and then Treatment 1 of AZD5004.	Drug: AZD5004; Participants will receive oral tablets of AZD5004 in Part A and Part B of the study as per arms they are assigned.; Other Names: ECC5004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To assess the safety and tolerability of AZD5004 following oral multiple ascending doses in healthy participants.	From screening (Day -28) to last follow up visit (Day 120)
Part B: Maximum observed plasma (peak) drug concentration (Cmax) of AZD5004	To evaluate the Cmax of 2 treatments of AZD5004 in healthy participants.	From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
Part B: Area under the concentration-curve from time zero to the last quantifiable concentration (AUClast)	To evaluate the AUClast of 2 treatments of AZD5004 in healthy participants.	From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
Part B: Area under concentration-time curve from time 0 to infinity (AUCinf)	To evaluate the AUCinf of 2 treatments of AZD5004 in healthy participants.	From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
Part B: Time to reach maximum observed concentration (tmax)	To evaluate the tmax of 2 treatments of AZD5004 in healthy participants.	From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Maximum observed plasma (peak) drug concentration (Cmax) of AZD5004	To characterize the Cmax of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Area under the concentration-curve from time zero to the last quantifiable concentration (AUClast)	To characterize the AUClast of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Area under concentration time curve in the dosing interval (AUCtau)	To characterize the AUCtau of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Amount of unchanged drug excreted into urine from time t1 to time t2 (Ae[t1-t2])	To characterize the Ae(t1-t2) of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Percentage of dose excreted unchanged in urine from time t1 to time t2 (fe[t1-t2])	To characterize the fe(t1-t2) of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Renal clearance (CLR)	To characterize the CLR of multiple ascending doses of AZD5004 in healthy participants.	From Day 1 to last follow up visit (Day 120)
Part A: Percentage change from Baseline in body weight (kg)	To assess the effects of AZD5004 compared to placebo on body weight change from baseline.	Baseline (Day - 2) to Days 49, 91, and 106
Part A: Absolute change from Baseline in body weight (kg)	To assess the effects of AZD5004 compared to placebo on body weight change from baseline.	Baseline (Day - 2) to Days 49, 91, and 106
Part A: Percentage change from Baseline in Body Mass Index (BMI) (kg/m^2)	To assess the effects of AZD5004 compared to placebo on body weight change from baseline.	Baseline (Day - 2) to Days 49, 91, and 106
Part A: Absolute change from Baseline in BMI (kg/m^2)	To assess the effects of AZD5004 compared to placebo on body weight change from baseline.	Baseline (Day - 2) to Days 49, 91, and 106
Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To evaluate the safety and tolerability of 2 treatments of AZD5004 in healthy participants.	From screening (Day -28) to last follow up visit (Day 14)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Actual): March 6, 2025
• Study Completion (Actual): March 6, 2025

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Type 2 Diabetes
• Other Study ID Numbers: D7260C00004

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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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