A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 Following Single and Multiple Ascending Doses Via Oral Administration to Healthy Participants

NCT06122714 | Completed Phase 1 FDA Drug

• 1 other identifier: D9440C00001
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of AZD4144 administered orally in healthy participants.

Conditions

Healthy Participants

Keywords

Single ascending dose (SAD); Multiple ascending dose (MAD)

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events (AEs)

  To assess the safety and tolerability of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B)

  Part A: From screening (Day -28 to Day -2) to Day 10; Part B: From screening (Day -28 to Day-2) to Day 20

Secondary Outcomes (5)

• Maximum observed plasma (peak) drug concentration (Cmax)

  Part A: Day 1 to Day 4. and Day 10; Part B: Day 1 to Day 15 and Day 20

• Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)

  Part A: Day 1 to Day 4. and Day 10; Part B: Day 1 to Day 15 and Day 20

• Area under plasma concentration-time curve from zero to infinity (AUC0-inf)

  Part A: Day 1 to Day 4. and Day 10; Part B: Day 1 to Day 15 and Day 20

• Renal clearance of drug from plasma (CLR)

  Part A: Day 1 to Day 4. and Day 10; Part B: Day 1 to Day 15 and Day 20

• PD analysis: Levels of disease-specific biomarkers

  Part A: Day 1 to Day 4 and Day 10; Part B: Day -1, Day 1 to Day 4, Day 12 to Day 15 and Day 20

Study Arms (18)

Part A1 (healthy participants) Cohort 1

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 2

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 3

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 4

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 5

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 6

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A1 (healthy participants) placebo

PLACEBO COMPARATOR

Participants will receive matching Placebo.

Drug: Placebo Part A

Part A2 (healthy Japanese participants) Cohort 1

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A2 (healthy Japanese participants) Cohort 2

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A2 (healthy Japanese participants) placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo Part A

Part A3 (healthy Chinese participants) Cohort 1

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144 Part A

Part A3 (healthy Chinese participants) placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo Part A

Part B1 (healthy participants) Cohort 1

EXPERIMENTAL

Participants will receive one multiple ascending dose of AZD4144.

Drug: AZD4144 Part B

Part B1 (healthy participants) Cohort 2

EXPERIMENTAL

Participants will receive one multiple ascending dose of AZD4144.

Drug: AZD4144 Part B

Part B1 (healthy participants) Cohort 3

EXPERIMENTAL

Participants will receive one multiple ascending dose of AZD4144.

Drug: AZD4144 Part B

Part B1 (healthy participants) placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo Part B

Part B2 (healthy Japanese participants) Cohort 1

EXPERIMENTAL

Participants will receive one multiple ascending dose of AZD4144.

Drug: AZD4144 Part B

Part B2 (healthy Japanese participants) placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo Part B

Interventions

AZD4144 Part A DRUG

Part A: Participants will be administered a single oral dose on Day 1.

Part A1 (healthy participants) Cohort 1; Part A1 (healthy participants) Cohort 2; Part A1 (healthy participants) Cohort 3; Part A1 (healthy participants) Cohort 4; Part A1 (healthy participants) Cohort 5; Part A1 (healthy participants) Cohort 6; Part A2 (healthy Japanese participants) Cohort 1; Part A2 (healthy Japanese participants) Cohort 2; Part A3 (healthy Chinese participants) Cohort 1

AZD4144 Part B DRUG

Part B: Participants will be administered a single dose on Day 1, and repeated dosing will commence from Day 4 until Day 11 (inclusive) and a single dose on Day 12.

Part B1 (healthy participants) Cohort 1; Part B1 (healthy participants) Cohort 2; Part B1 (healthy participants) Cohort 3; Part B2 (healthy Japanese participants) Cohort 1

Placebo Part A DRUG

Part A: Participants will be administered a single oral dose of matching placebo on Day 1.

Part A1 (healthy participants) placebo; Part A2 (healthy Japanese participants) placebo; Part A3 (healthy Chinese participants) placebo

Placebo Part B DRUG

Part B: Participants will be administered a single dose of matching placebo on Day 1, and repeated dosing will commence from Day 4 until Day 11 (inclusive) and a single dose on Day 12.

Part B1 (healthy participants) placebo; Part B2 (healthy Japanese participants) placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females must have a negative pregnancy test, must not be lactating and must be of non-childbearing potential.
• Have a BMI between 18 and 32 kg/m2 inclusive at both Screening and Admission and weigh at least 45 kg at Screening.
• For healthy Japanese cohorts (Part A2 and Part B2): healthy male and female (of non-childbearing potential) participants are to be Japanese, defined as having both parents and four grandparents who are Japanese. This included second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
• For healthy Chinese cohort (Part A3): healthy male and female (of non-childbearing potential) Chinese participants for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study.
• History or presence of gastrointestinal, hepatic or renal 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.
• Clinically significant serious active and chronic infections.
• Bacillus Calmette-Guérin vaccine within one year prior to signing the ICF.
• Any abnormal laboratory values at the Screening Visit.
• Any positive result on Screening for serum Hepatitis B surface antigen (HBsAg), anti-Hepatitis B core (HBc), hepatitis C antibody, or Human Immunodeficiency Virus (HIV).
• Any cardiac abnormalities.
• History of alcohol abuse or drug abuse.
• Current smokers or those who have smoked or used nicotine products.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Clinical signs and symptoms consistent with COVID-19.
• Previous bone marrow transplant
• Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Brooklyn, Maryland, 21225, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2023
• First Posted: November 8, 2023
• Study Start: November 7, 2023
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (2)