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

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06122714

Collaborator

Parexel (Industry)

104

Enrollment

Locations

Arms

8.8

Anticipated Duration (Months)

Patients Per Site

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: AZD4144 Part A Drug: AZD4144 Part B Drug: Placebo Part A Drug: Placebo Part B	Phase 1

Detailed Description

This is a Phase I, first time-in human (FTiH), randomised, single-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) sequential group study in healthy participants.

Part A consists of 3 parts:

Part A1 (healthy participants) Part A2 (healthy Japanese participants) and Part A3 (healthy Chinese participants)

Part B consists of 2 parts:

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

Both Part A and Part B of the study will comprise of a screening period of maximum 28 days. The treatment period would last from Day -1 to Day 4 in Part A and from Day -1 to Day 15 in Part B of the study. A follow up visit will be performed on Day 10 + 3 days for Part A and on Day 20 + 3 days for Part B.

Each participant will participate for about 6 weeks in Part A of the study and for about 7 weeks in Part B of the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase I Randomised, Single-blind, Placebo-controlled, and Sequential Group Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 Following Single and Multiple Ascending Doses Via Oral Administration to Healthy Participants

Anticipated Study Start Date :

Nov 14, 2023

Anticipated Primary Completion Date :

Aug 9, 2024

Anticipated Study Completion Date :

Aug 9, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A1 (healthy participants) Cohort 1 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A1 (healthy participants) Cohort 2 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A1 (healthy participants) Cohort 3 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A1 (healthy participants) Cohort 4 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A1 (healthy participants) Cohort 5 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A1 (healthy participants) Cohort 6 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Placebo Comparator: Part A1 (healthy participants) placebo Participants will receive matching Placebo.	Drug: Placebo Part A Part A: Participants will be administered a single oral dose of matching placebo on Day 1.
Experimental: Part A2 (healthy Japanese participants) Cohort 1 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Experimental: Part A2 (healthy Japanese participants) Cohort 2 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Placebo Comparator: Part A2 (healthy Japanese participants) placebo Participants will receive matching placebo.	Drug: Placebo Part A Part A: Participants will be administered a single oral dose of matching placebo on Day 1.
Experimental: Part A3 (healthy Chinese participants) Cohort 1 Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144 Part A Part A: Participants will be administered a single oral dose on Day 1.
Placebo Comparator: Part A3 (healthy Chinese participants) placebo Participants will receive matching placebo.	Drug: Placebo Part A Part A: Participants will be administered a single oral dose of matching placebo on Day 1.
Experimental: Part B1 (healthy participants) Cohort 1 Participants will receive one multiple ascending dose of AZD4144.	Drug: AZD4144 Part B Part B: Participants will be administered a single dose on Day 1, and repeated dosing will commence from Day 4 until Day 12 (inclusive).
Experimental: Part B1 (healthy participants) Cohort 2 Participants will receive one multiple ascending dose of AZD4144.	Drug: AZD4144 Part B Part B: Participants will be administered a single dose on Day 1, and repeated dosing will commence from Day 4 until Day 12 (inclusive).
Experimental: Part B1 (healthy participants) Cohort 3 Participants will receive one multiple ascending dose of AZD4144.	Drug: AZD4144 Part B Part B: Participants will be administered a single dose on Day 1, and repeated dosing will commence from Day 4 until Day 12 (inclusive).
Placebo Comparator: Part B1 (healthy participants) placebo Participants will receive matching placebo.	Drug: Placebo Part B 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 12 (inclusive).
Experimental: Part B2 (healthy Japanese participants) Cohort 1 Participants will receive one multiple ascending dose of AZD4144.	Drug: AZD4144 Part B Part B: Participants will be administered a single dose on Day 1, and repeated dosing will commence from Day 4 until Day 12 (inclusive).
Placebo Comparator: Part B2 (healthy Japanese participants) placebo Participants will receive matching placebo.	Drug: Placebo Part B 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 12 (inclusive).

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [Part A: From screening (Day -28 to Day -2) to Day 10; Part B: From screening (Day -28 to Day-2) to Day 20]
To assess the safety and tolerability of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B)

Secondary Outcome Measures

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]
To characterise the single dose and steady state PK of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B).
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]
To characterise the single dose and steady state PK of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B)
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]
To characterise the single dose and steady state PK of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B)
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]
To characterise the single dose and steady state PK of AZD4144 following oral administration of single and multiple ascending doses (Part A and Part B)
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]
To assess the effect of AZD4144 on levels of disease-specific biomarkers.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

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.

Exclusion criteria:

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.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:

Previous bone marrow transplant
Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Glendale	California	United States	91206
2	Research Site	Brooklyn	Maryland	United States	21225

Sponsors and Collaborators

AstraZeneca
Parexel

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT06122714

Other Study ID Numbers:

D9440C00001

First Posted:

Nov 8, 2023

Last Update Posted:

Nov 8, 2023

Last Verified:

Nov 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by AstraZeneca

Single ascending dose (SAD)

Multiple ascending dose (MAD)

Study Results

No Results Posted as of Nov 8, 2023