Phase I Study to Assess the Effect on Healthy Male Volunteers of Ketoconazole on the Pharmacokinetics of a Single Dose of AZD5069 Administered Orally.

NCT01735240 | Completed Phase 1

• 1 other identifier: D3550C00011
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Asthma,; Pharmacokinetics,; Cmax,; Tmax,; λz,; AUC,; Ketoconazole,; Metabolite

Keywords

Phase I,; healthy volunteers,; fixed-sequence,; open-label,; ketoconazole,; combination,; safety

Outcome Measures

Primary Outcomes (2)

• 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)

  (AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution.

  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.

• Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069)

  Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.

Secondary Outcomes (2)

• Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole

  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

• 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.

  Up to 2 months

Study Arms (1)

First AZD5069, then Ketoconazole + AZD5069

EXPERIMENTAL

AZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days)

Drug: AZD5069; Drug: Ketoconazole

Interventions

AZD5069 DRUG

AZD5069 15 mg (3x5 mg capsules) single administration

First AZD5069, then Ketoconazole + AZD5069

Ketoconazole DRUG

Ketoconazole 400 mg (2x200 mg tablets)

First AZD5069, then Ketoconazole + AZD5069

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Unknown Facility

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29856004 DERIVED

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Asthma

Interventions

N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide; Ketoconazole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bengt Larsson, Dr.

  AstraZeneca Pharmaceutical

  STUDY DIRECTOR

• Gillian Pilbrow

  AstraZeneca Pharmaceutical

  STUDY CHAIR

• Leonard Siew, DR.

  Quintiles Drug Research Unit at Guy's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: November 28, 2012
• Study Start: December 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: June 25, 2015

Record last verified: 2015-06

Locations

GB (1)