Clinical trial NCT06304961: A Study to Investigate Relative Bioavailability of Two Different Dosage Forms for Tozorakimab Via Subcutaneous Administration in Healthy Volunteers
Official title: A Randomised, Single-dose, Parallel Group Study in Healthy Volunteers to Assess the Relative Bioavailability of Two Different Dosage Forms for Tozorakimab Via Subcutaneous Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Human immunoglobulin G1 monoclonal antibody
Chronic Obstructive Pulmonary Disease
Asthma
Pharmacokinetics
Bioavailability
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-03-12
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a phase I, randomised, open-label, single-dose, single-centre, parallel group study investigating the relative bioavailability of two dosage forms of tozorakimab (test dosage form and reference dosage form).

The study will comprise of:

1. A screening period of 28 days
2. A Treatment period of 1 day
3. Ambulatory visits on scheduled days

c. A final follow-up visit on Day 113 (Week 16)

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Area under the concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Area under the concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Maximum observed drug concentration (Cmax)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
Secondary outcomes:
measure: Time to reach peak or maximum observed concentration following tozorakimab administration (tmax)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Terminal elimination half-life (t1/2)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Terminal rate constant (λz)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Apparent total body clearance (CL/F)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: Day 1 (Pre-dose), Days 3, 4, 5, 7, 8, 9, 15, 29, 43, 57, 85 and 113 (Post-dose).
measure: Number of participants with adverse events (AEs)
timeFrame: From screening (Day -28) to last follow-up visit (Day 113- approximately 21 weeks).
measure: Number of participants with presence of Anti-Drug Anitbodies (ADAs)
timeFrame: Day 1 (Pre-dose), Days 29, 57 and 113 (Post-dose).
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: