Clinical trial NCT01989520: Study to Investigate Relative Bioavailability of up to Five Different Formulations of AZD5069
Official title: An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Uncontrolled and Persistent Asthma
Keywords: Relative bioavailability, Healthy volunteers, Neutrophils
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-11-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Study to investigate relative bioavailability of up to five different formulations of AZD5069

Detailed description: An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers

Eligibility criteria: Inclusion Criteria:

1. Healthy male and/or female volunteers aged 18 to 50 years (inclusive).
2. Non-smokers or ex-smokers with no smoking history for the last 3 months prior to screening.
3. Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at screening; minimum (min) weight 50 kg and maximum (max) weight 100 kg.
4. Healthy volunteers with neutrophil counts within the laboratory range at screening.

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Exclusion Criteria:

1. A definite or suspected personal history of severe allergy, intolerance or hypersensitivity or ongoing allergy to drugs with a similar chemical structure or class to AZD5069 and/or the excipients, as judged to be clinically relevant by the Investigator.
2. Healthy volunteers who have previously received AZD5069.
3. Volunteers with latent tuberculosis as suggested by their history and judged by the Investigator; confirmatory testing with eg, Quantiferon(R) -TB Gold may be done if required.
4. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to the first administration of the IP -

Primary outcomes:
measure: Description of pharmacokinetics of AZD5069 and its metabolite in terms of area under plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration and extrapolated to infinity (AUC(0-last) and AUC)
timeFrame: Samples taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
measure: Description of pharmacokinetics of AZD5069 and its metabolite in terms of observed maximum plasma concentration (Cmax), plasma concentration measured at 12 hours (C12h), Cmax/C12h ratio, Cmax/AUC ratio, terminal rate constant (λz)
timeFrame: Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
measure: Description of pharmacokinetics of AZD5069 and its metabolite in terms of terminal half-life (t½λz), time to reach maximum plasma concentration (tmax)
timeFrame: Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
measure: Description of pharmacokinetics of AZD5069 and its metabolite in terms of apparent systemic clearance (CL/F) (AZD5069 only), and apparent volume of distribution (Vz/F) (AZD5069 only)
timeFrame: Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Secondary outcomes:
measure: Description of effect on neutrophils in terms of circulating neutrophil numbers reported as absolute circulating neutrophil counts (ANC). The minimum absolute neutrophil count (ANCmin) and the time to ANCmin (ANCtmin)
timeFrame: Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose
measure: Description of effect on neutrophils in terms of mean of ANC values from predose to 24 hours postdose (ANCmean), the minimum of the ANC ratio values (ANCmin,ratio)
timeFrame: Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose
measure: Description of effect on neutrophils in terms of the mean of ANC ratio values calculated baseline to 24 hours post dose (ANCmean,ratio)
timeFrame: Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles London UK
name: Olufeyikemi Oluwayi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Astrazeneca Mölndal, Sweden
name: Bengt Larssons, MD
role: STUDY_DIRECTOR
References:
citation: Cullberg M, Arfvidsson C, Larsson B, Malmgren A, Mitchell P, Wahlby Hamren U, Wray H. Pharmacokinetics of the Oral Selective CXCR2 Antagonist AZD5069: A Summary of Eight Phase I Studies in Healthy Volunteers. Drugs R D. 2018 Jun;18(2):149-159. doi: 10.1007/s40268-018-0236-x.