Clinical trial NCT06555822: A Study to Investigate Multiple Ascending Doses and Relative Bioavailability of AZD5004 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Obesity
Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-08-15
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From screening (Day -28) to last follow up visit (Day 120)
measure: Part B: Maximum observed plasma (peak) drug concentration (Cmax) of AZD5004
timeFrame: From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
measure: Part B: Area under the concentration-curve from time zero to the last quantifiable concentration (AUClast)
timeFrame: From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
measure: Part B: Area under concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
measure: Part B: Time to reach maximum observed concentration (tmax)
timeFrame: From Day 1 (Treatment Period 1) to Day 13 (end of Treatment Period 2)
Secondary outcomes:
measure: Part A: Maximum observed plasma (peak) drug concentration (Cmax) of AZD5004
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Area under the concentration-curve from time zero to the last quantifiable concentration (AUClast)
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Area under concentration time curve in the dosing interval (AUCtau)
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Amount of unchanged drug excreted into urine from time t1 to time t2 (Ae[t1-t2])
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Percentage of dose excreted unchanged in urine from time t1 to time t2 (fe[t1-t2])
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Renal clearance (CLR)
timeFrame: From Day 1 to last follow up visit (Day 120)
measure: Part A: Percentage change from Baseline in body weight (kg)
timeFrame: Baseline (Day - 2) to Days 49, 91, and 106
measure: Part A: Absolute change from Baseline in body weight (kg)
timeFrame: Baseline (Day - 2) to Days 49, 91, and 106
measure: Part A: Percentage change from Baseline in Body Mass Index (BMI) (kg/m^2)
timeFrame: Baseline (Day - 2) to Days 49, 91, and 106
measure: Part A: Absolute change from Baseline in BMI (kg/m^2)
timeFrame: Baseline (Day - 2) to Days 49, 91, and 106
measure: Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From screening (Day -28) to last follow up visit (Day 14)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: