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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: AZD4144 Part A; Drug: Placebo Part A; Drug: AZD4144 Part B; Drug: Placebo Part B

Study type: Interventional

Funder types: Industry

Identifiers

NCT06122714

D9440C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 95 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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:

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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95 participants in 18 patient groups, including a placebo group

Part A1 (healthy participants) Cohort 1

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 2

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 3

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 4

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 5

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) Cohort 6

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A1 (healthy participants) placebo

Placebo Comparator group

Description:

Participants will receive matching Placebo.

Treatment:

Drug: Placebo Part A

Part A2 (healthy Japanese participants) Cohort 1

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A2 (healthy Japanese participants) Cohort 2

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A2 (healthy Japanese participants) placebo

Placebo Comparator group

Description:

Participants will receive matching placebo.

Treatment:

Drug: Placebo Part A

Part A3 (healthy Chinese participants) Cohort 1

Experimental group

Description:

Participants will receive one single ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part A

Part A3 (healthy Chinese participants) placebo

Placebo Comparator group

Description:

Participants will receive matching placebo.

Treatment:

Drug: Placebo Part A

Part B1 (healthy participants) Cohort 1

Experimental group

Description:

Participants will receive one multiple ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part B

Part B1 (healthy participants) Cohort 2

Experimental group

Description:

Participants will receive one multiple ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part B

Part B1 (healthy participants) Cohort 3

Experimental group

Description:

Participants will receive one multiple ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part B

Part B1 (healthy participants) placebo

Placebo Comparator group

Description:

Participants will receive matching placebo.

Treatment:

Drug: Placebo Part B

Part B2 (healthy Japanese participants) Cohort 1

Experimental group

Description:

Participants will receive one multiple ascending dose of AZD4144.

Treatment:

Drug: AZD4144 Part B

Part B2 (healthy Japanese participants) placebo

Placebo Comparator group

Description:

Participants will receive matching placebo.

Treatment:

Drug: Placebo Part B