A Study to Investigate Relative Bioavailability of Two Different Dosage Forms for Tozorakimab Via Subcutaneous Administration in Healthy Volunteers

NCT06304961 | Completed Phase 1

• 1 other identifier: D9180C00011
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the relative bioavailability between two dosage forms of tozorakimab (test dosage form and reference dosage form) and to assess the pharmacokinetic (PK) profiles of both dosage forms.

Conditions

Healthy Participants

Keywords

Human immunoglobulin G1 monoclonal antibody; Chronic Obstructive Pulmonary Disease; Asthma; Pharmacokinetics; Bioavailability

Outcome Measures

Primary Outcomes (3)

• Area under the concentration-time curve from time 0 to infinity (AUCinf)

  To evaluate the relative bioavailability of two different dosage forms of tozorakimab (test and reference).

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Area under the concentration-curve from time 0 to the last quantifiable concentration (AUClast)

  To evaluate the relative bioavailability of two different dosage forms of tozorakimab (test and reference).

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Maximum observed drug concentration (Cmax)

  To evaluate the relative bioavailability of two different dosage forms of tozorakimab (test and reference).

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

Secondary Outcomes (7)

• Time to reach peak or maximum observed concentration following tozorakimab administration (tmax)

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Terminal elimination half-life (t1/2)

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Terminal rate constant (λz)

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Apparent total body clearance (CL/F)

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

• Apparent volume of distribution based on the terminal phase (Vz/F)

  Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).

Study Arms (2)

Tozorakimab Dosage form A (Test)

EXPERIMENTAL

Participants will receive a single dose of Tozorakimab Dosage form A via subcutaneous (SC) injection.

Biological: Tozorakimab

Tozorakimab Dosage form B (Reference)

EXPERIMENTAL

Participants will receive a single dose of Tozorakimab Dosage form B via SC injection.

Biological: Tozorakimab

Interventions

Tozorakimab BIOLOGICAL

Tozorakimab will be administered as a single SC dose on Day 1.

Tozorakimab Dosage form A (Test); Tozorakimab Dosage form B (Reference)

Eligibility Criteria

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

You may qualify if:

• Healthy male and female participants aged 18 to 55 years.
• All females must have a negative pregnancy test at the screening visit and on admission to the Clinical Unit.
• Females of childbearing potential must not be lactating and, if heterosexually active, must agree to use an approved method of highly effective contraception.
• Females of non-childbearing potential must be confirmed at the screening visit.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
• Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive.
• Intact normal skin without potentially obscuring tattoos, scars, etc, at the injection site.

You may not qualify if:

• History of any clinically significant disease or disorder (including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator).
• Any clinically significant abnormal findings in vital signs at the screening visit and/or admission (Day -1) to the Clinical Unit, as judged by the investigator.
• Any clinically significant abnormalities on 12-lead ECG at the screening visit and/or admission (Day -1) to the Clinical Unit, as judged by the investigator.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 6 months prior to the screening visit, as judged by the investigator.
• Any clinically important illness, medical/surgical procedure, or trauma within 8 weeks of the screening visit, or any planned inpatient surgery or hospitalisation during the study period.
• Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to enrolment. Suspected malignancy or undefined neoplasms.
• Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
• Any laboratory values with the following deviations at the screening visit or on admission (Day -1) to the Clinical Unit.
• Any clinically significant abnormal findings in physical examination at screening and/or admission (Day -1), which, in the opinion of the investigator, may put the participant at risk because of their participation in the study or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
• History of known immunodeficiency disorder, including a positive test for Human immunodeficiency virus-1 (HIV-1) or HIV-2.
• History or treatment for hepatitis B or hepatitis C or any positive test result on screening for Hepatitis B surface antigen (HBsAg), anti- Hepatitis B core (HBc) antibodies, or anti-hepatitis C antibodies.
• Evidence of active or latent Tuberculosis (TB).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: April 8, 2024
• Primary Completion: September 9, 2024
• Study Completion: September 9, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer 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 anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

DE (1)