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

Sponsor
AstraZeneca (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05644600
Collaborator
Parexel (Industry)
18
1
3
1.6
11.4

Study Details

Study Description

Brief Summary

The study is intended to quantify the effect of co-administration of AZD5055 on exposures of nintedanib in healthy subjects.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This study will be an open-label, randomised, 3-period, 3-treatment, crossover study in healthy subjects (males and females of non-childbearing potential), performed at a single Clinical Unit.

The study will comprise:
  • A Screening period of 28 days.

  • Three periods during which subjects will participate from Day -1 of Period 1 to 72 hours after the nintedanib dose in Period 3. In each period, the subjects will receive nintedanib in the morning of Day 1. In treatment sequences in which AZD5055 will be co administered with nintedanib, AZD5055 will be administered immediately before the nintedanib dose on Day 1.

A Follow-up Visit, 6 ±1 days after the last dose of nintedanib in the last period.

All subjects will be randomised 1:1:1 to 3 sequences (ABC, BCA, CAB). Each sequence consists of three treatment periods (Period 1, Period 2, Period 3).

Treatment A: Nintedanib soft capsules, fasted state. Treatment B: Dose B oral suspension of AZD5055 will be given immediately followed by nintedanib soft capsules in the fasted state.

Treatment C: Dose C oral suspension of AZD5055 will be given immediately followed by nintedanib soft capsules in the fasted state.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Randomized, Three-Period Study in Healthy Subjects to Investigate the Effect of AZD5055 on the Pharmacokinetics of Nintedanib.
Anticipated Study Start Date :
Jan 10, 2023
Anticipated Primary Completion Date :
Feb 27, 2023
Anticipated Study Completion Date :
Feb 27, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment A

The subjects will receive Nintedanib soft capsules, fasted state.

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

Experimental: Treatment B

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

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

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

Experimental: Treatment C

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

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

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

Outcome Measures

Primary Outcome Measures

  1. Maximum observed plasma (peak) drug concentration (Cmax) [Day 1 - 9]

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

  2. Area under plasma concentration time curve from zero to infinity (AUCinf) [Day 1 - 9]

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

  3. Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) [Day 1 - 9]

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

Secondary Outcome Measures

  1. Maximum observed plasma (peak) drug concentration (Cmax) [Day 1-9]

    The PK of AZD5055 after single Dose B or Dose C doses co-administered with a single oral dose of nintedanib will be evaluated.

  2. Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) [Day 1-9]

    The PK of AZD5055 after single Dose B or Dose C doses co-administered with a single oral dose of nintedanib will be evaluated.

  3. Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUCinf) [Day 1-9]

    The PK of AZD5055 after single Dose B or Dose C doses co-administered with a single oral dose of nintedanib will be evaluated.

  4. Outcome measure tittle should be always specific "Number of subject with Adverse event (AE) and serious Adverse event (SAE)" [SAEs: From Screening (Day -28 to -2) to Day -1 of Period 1 AEs: From Day 1 untill follow up (Day 13)]

    The safety following single oral doses of nintedanib versus nintedanib co-administered with AZD5055 in healthy subjects will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Healthy nonsmoking male and female (of non-childbearing potential) subjects 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 subjects 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 subject at risk because of participation in the study, or influence the results or the subject'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 .

  1. Any positive result on Screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and HIV antibody.

  2. 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.

  3. 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.

  4. Subjects who have previously received AZD5055.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Glendale United Kingdom 91206

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:
NCT05644600
Other Study ID Numbers:
  • D8960C00003
First Posted:
Dec 9, 2022
Last Update Posted:
Dec 9, 2022
Last Verified:
Nov 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 9, 2022