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

NCT05644600 | Terminated Phase 1

• 2 other identifiers: D8960C000032022-003116-84
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Drug-drug interaction; Idiopathic pulmonary fibrosis; Interstitial lung diseases with progressive fibrosis; Porcupine inhibitor; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

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

  The effect of AZD5055 on the PK of nintedanib alone and in combination AZD5055 will be assessed.

  Day 1 - 9

• Area under plasma concentration time curve from zero to infinity (AUCinf)

  The effect of AZD5055 on the PK of nintedanib alone and in combination AZD5055 will be assessed.

  Day 1 - 9

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

  The effect of AZD5055 on the PK of nintedanib alone and in combination AZD5055 will be assessed.

  Day 1 - 9

Secondary Outcomes (7)

• Cmax of AZD5055 (Part A only)

  Day 1-9

• AUCinf of AZD5055 (Part A only)

  Day 1-9

• AUClast of AZD5055 (Part A only)

  Day 1-9

• Cmax of ninetedanib alone and in combination AZD5055 (Part B only)

  Day 1-6

• AUCinf of ninetedanib alone and in combination AZD5055 (Part B only)

  Day 1-6

Study Arms (4)

Treatment A

EXPERIMENTAL

The subjects will receive Nintedanib soft capsules, fasted state.

Drug: Nintedanib

Treatment B

EXPERIMENTAL

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

Drug: Nintedanib; Drug: AZD5055

Treatment C

EXPERIMENTAL

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

Drug: Nintedanib; Drug: AZD5055

Treatment D

EXPERIMENTAL

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.

Drug: AZD5055

Interventions

Nintedanib DRUG

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

Treatment A; Treatment B; Treatment C

AZD5055 DRUG

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

Treatment B; Treatment C; Treatment D

Eligibility Criteria

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

You may qualify if:

• Healthy nonsmoking male and female (of non-childbearing potential) participants aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test, must not be lactating and must be of non childbearing potential.
• 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.

You may not qualify if:

• 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.
• 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.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP (Investigational Medicinal Product).
• Untreated TB (Tuberculosis) or a positive result for the IGRA (Interferon Gamma Release Assay) (ie, QuantiFERON TB Gold).
• 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) .
• 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).
• 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.
• History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.
• History of a traumatic fracture within 6 months of Screening.
• 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 .
• \. 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.
• \. 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.
• \. 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.
• \. Subjects who have previously received AZD5055.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, 91206, United Kingdom

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 9, 2022
• Study Start: May 26, 2023
• Primary Completion: July 17, 2023
• Study Completion: July 17, 2023
• Last Updated: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 deidentified individual subject-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (1)