Clinical trial NCT01735240: Phase I Study to Assess the Effect on Healthy Male Volunteers of Ketoconazole on the Pharmacokinetics of a Single Dose of AZD5069 Administered Orally.
Official title: An Open-label, Fixed-sequence, Single-centre Phase I Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of AZD5069 After Oral Administration of a Single Dose AZD5069 to Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma,
Pharmacokinetics,
Cmax,
Tmax,
λz,
AUC,
Ketoconazole,
Metabolite
Keywords: Phase I,
healthy volunteers,
fixed-sequence,
open-label,
ketoconazole,
combination,
safety
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-11-28
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of the study is to compare the change of the AZD5069 Pharmacokinetic profile when administered with ketoconazole. Subjects will be treated first with AZD5069 only followed by a washout period before starting with the combined treatment (both ketoconazole and AZD5069).

Detailed description: An open-label, fixed-sequence, single-centre phase I study to assess the effect of ketoconazole on the pharmacokinetics of AZD5069 after oral administration of a single dose AZD5069 to healthy male volunteers

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers aged 18 to 50 years (inclusive).
* Veins suitable for cannulation or repeated venipuncture.
* Healthy volunteers with neutrophil counts within the laboratory normal reference range at Screening
* Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at screening; minimum weight 50 kg and maximum weight 100 kg.
* Non-smokers or ex-smokers with no smoking history for the last 3 months prior to screening and a smoking history of less than 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for 1 year) at screening.

Exclusion Criteria:

* Healthy volunteers with latent tuberculosis as suggested by their history and judged by the Investigator
* Healthy volunteers who belong to a high-risk group for HIV infection.
* Known or suspected history of significant drug abuse as judged by the Investigator.
* History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
* Plasma donation within 1 month of screening or any blood donation/blood loss \>500 mL during the 3 months and/or 1350 mL within the 12 months prior to screening.

Primary outcomes:
measure: Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole)
timeFrame: Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.
measure: Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069)
timeFrame: Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.
Secondary outcomes:
measure: Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole
timeFrame: Day 1, 2, 3 at predose, 4, 8, 12, 24, 48 hours post dose in period 1 and Day 1, 2, 3, 4 at predose, 4, 8, 12, 24, 48 hours post dose
measure: Safety of AZD5069 (15 mg) in combination with Ketoconazole by assessing a panel of adverse events measures: laboratory assessments, vital signs, physical examination and 12-led electrocardiogram.
timeFrame: Up to 2 months
Other outcomes:
Locations:
city: London
country: United Kingdom
Study officials:
affiliation: AstraZeneca Pharmaceutical
name: Bengt Larsson, Dr.
role: STUDY_DIRECTOR
affiliation: AstraZeneca Pharmaceutical
name: Gillian Pilbrow
role: STUDY_CHAIR
affiliation: Quintiles Drug Research Unit at Guy's Hospital
name: Leonard Siew, DR.
role: PRINCIPAL_INVESTIGATOR
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.