A Study to Assess the Effect of AZD5055 on the Pharmacokinetics (PK) of Nintedanib in Healthy Participants.

NCT ID: NCT05644600

Last Updated: 2024-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-26
• Study Completion Date: 2023-07-17

Brief Summary

The study is intended to quantify the effect of co-administration and staggered dosing of AZD5055 and nintedanib on exposures of nintedanib in healthy participants.

Detailed Description

This study will be an open-label, randomised, crossover study in healthy participants (males and females of non-childbearing potential).

The study will comprise two parts: Part A and Part B.

The study will include a screening period of 28 days for both Part A and Part B.

Part A will be a 3-period (Periods 1, 2, 3), 3-treatment (Treatments A, B, C) crossover study, performed at a single clinical unit. During the 3 periods (Periods 1, 2, 3) participants will participate from Day -1 of Period 1 to 72 hours after the nintedanib dose in Period 3. In each period, the participants will receive AZD5055 immediately before the nintedanib dose in the morning of the first day. In Part A, all participants will be randomised to one of 3 sequences.

An interim analysis of data from Part A will be performed, and Part B (conducted only if an interaction between AZD5055 and nintedanib is observed in Part A) will be a 2-period (Periods 1, 2), 2-treatment (Treatments A, D) crossover study, performed at 2 clinical units. In each period, the participants in Treatment D will be dosed with AZD5055 4 hours after the nintedanib dose in the morning of the first day. In Part B, all participants will be randomised to one of 2 sequences.

For both Part A and Part B, there will be a minimum washout period of approximately 72 hours between each AZD5055 dose administration. And, a follow-up visit will be performed, at 6 ± 1 days after the last dose of nintedanib in last period.

Conditions

Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment A

The subjects will receive Nintedanib soft capsules, fasted state.

Group Type: EXPERIMENTAL

Nintedanib

Intervention Type: DRUG

The subjects will be administered Nintedanib soft capsules single oral dose in the morning of Day 1 in fasted state.

Treatment B

The subjects will receive dose B of the oral suspension of AZD5055 immediately followed by nintedanib in the fasted state.

Group Type: EXPERIMENTAL

Nintedanib

Intervention Type: DRUG

The subjects will be administered Nintedanib soft capsules single oral dose in the morning of Day 1 in fasted state.

AZD5055

Intervention Type: DRUG

The subjects will be administered AZD5055 as single oral dose on Day 1 in the fasted state.

Treatment C

The subjects will receive dose C of the oral suspension of AZD5055 immediately followed by nintedanib in the fasted state.

Group Type: EXPERIMENTAL

Nintedanib

Intervention Type: DRUG

The subjects will be administered Nintedanib soft capsules single oral dose in the morning of Day 1 in fasted state.

AZD5055

Intervention Type: DRUG

The subjects will be administered AZD5055 as single oral dose on Day 1 in the fasted state.

Treatment D

The subjects will receive dose C of the oral suspension of AZD5055 4 hours after nintedanib in the fasted state.

Participants would remain in the fasted state until 1.5 hours after AZD5055 administration.

Group Type: EXPERIMENTAL

AZD5055

Intervention Type: DRUG

The subjects will be administered AZD5055 as single oral dose on Day 1 in the fasted state.

Interventions

Nintedanib

The subjects will be administered Nintedanib soft capsules single oral dose in the morning of Day 1 in fasted state.

Intervention Type: DRUG

AZD5055

The subjects will be administered AZD5055 as single oral dose on Day 1 in the fasted state.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Healthy nonsmoking male and female (of non-childbearing potential) participants aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.

2. Females must have a negative pregnancy test, must not be lactating and must be of non childbearing potential.

3. Male participants and their woman partners of childbearing potential must be willing to use highly effective contraception measures and must refrain from donating sperm or fathering a child.

Exclusion Criteria

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.

2. History or presence of chronic gastrointestinal, hepatic, or renal disease, any acute disease in these organs, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP (Investigational Medicinal Product).

4. Untreated TB (Tuberculosis) or a positive result for the IGRA (Interferon Gamma Release Assay) (ie, QuantiFERON TB Gold).

5. Individuals with chronic infections (eg, urinary tract infection) or who are at increased risk of infection (eg, surgery, trauma, severe dental disease, or significant infection) .

6. History of severe COVID-19 (corona virus) infection requiring hospitalisation within the last 12 months prior to Screening, or clinical history compatible with Long COVID-19 (symptoms beyond 12 weeks of acute infection).

7. Has received live or live attenuated vaccine in the 30 days prior to dosing, the first dose of COVID-19 vaccine within 30 days prior to randomisation, or a COVID-19 vaccine second or booster vaccination within 10 days of Screening.

8. History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.

9. History of a traumatic fracture within 6 months of Screening.

10. Any laboratory values with the following deviations:

(1) Alanine aminotransferase > ULN (2) Aspartate aminotransferase > ULN (3) Total bilirubin > ULN (4) White blood cell count < 3.5 × 109/L (5) Platelet < LLN (6) eGFR < 90 ml/min/1.73 m2 (Cockroft-Gault or CKD-EPI formula) 11. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (Electrocardiogram) and any clinically important abnormalities in the 12-lead ECG .

12. Any positive result on Screening for active hepatitis A, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or HIV antibody, or any known chronic/active liver diseases.

13. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5055 or nintedanib.

14. Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life.

15. Subjects who have previously received AZD5055.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Glendale, , United Kingdom

Countries

United Kingdom

Other Identifiers

2022-003116-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8960C00003

Identifier Type: -

Identifier Source: org_study_id