Assess Safety, Tolerability and PK of AZD3199 in Japanese

A Phase I, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Centre Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of AZD3199 Given Once Daily as Inhaled Formulation Via Turbuhaler to Japanese Healthy Men

The primary objective of the study is to investigate the safety and tolerability of single and multiple once daily ascending doses of AZD3199 delivered as dry powder via the Turbuhaler inhaler in healthy male Japanese subjects by assessment of incidence and nature of adverse events (AEs), clinically significant abnormalities in ECG parameters, blood pressure (BP), pulse rate, lung function parameters, body temperature and laboratory variables (clinical chemistry, haematology and urinalysis). The secondary objectives of the study are to investigate the pharmacokinetics (PK) of single and multiple ascending doses of AZD3199 by assessment of the degree of accumulation, dose proportionality and time linearity in healthy Japanese subjects, and to investigate systemic β 2- adrenoreceptor mediated effects of single and multiple ascending doses of AZD3199 by assessment of potassium and lactate concentrations, tremor and palpitations, heart rate, QTc, pulse rate, blood pressure and FEV1.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AZD3199 Turbuhaler®; Drug: Placebo Turbuhaler®

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Berkshire
    • Slough, Berkshire, United Kingdom
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Be healthy Japanese volunteers, both of the volunteer's parents, and all grandparents must be Japanese. The volunteer must have been born in Japan, have a valid Japanese passport and must not have lived outside Japan for for more than 5 years.
• BMI 18 - 27, Weight 50 - 85 kg
• Be non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for >6 months prior to study start.
• Clinical normal physical findings

Exclusion Criteria:

• Any clinically significant disease or disorder
• Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, ECG or lung function at baseline
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes.
• Use of any medication (including OTC), herbal preparations, vitamins or nutritional supplements within 2 weeks prior to Visit 2, except for occasional intake of paracetamol (maximum daily dose of 4 g)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Dry powder for oral inhalation	Drug: AZD3199 Turbuhaler®; 240, 720 and 2160 μ g, single and multiple (o.d. for 12 days)
PLACEBO_COMPARATOR: 2; Dry powder for oral inhalation	Drug: Placebo Turbuhaler®; single and multiple (o.d. for 12 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety/Tolerability - adverse events (AEs), clinically significant abnormalities in ECG parameters, blood pressure (BP), pulse rate, lung function parameters, body temperature and laboratory variables (clinical chemistry, haematology and urinalysis)	During the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Parameters derived from plasma concentration and optionally urinary excretion of AZD3199.	During residential period
Pharmacodynamic Potassium and lactate concentrations, tremor and palpitations, heart rate, QTc, pulse rate, blood pressure, and forced expiratory volume in one second (FEV1).	During residential period

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Ronnie Beboso, Chiltern Clinical Research Unit (CCRU).

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Study Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (ESTIMATE): October 15, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 5, 2009
• Last Update Submitted That Met QC Criteria: May 4, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: tolerability; safety; PK; Phase I study; Single and Multiple Ascending Dose; Japanese Healthy Volunteers; AZD3199
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Agonists; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; AZD-3199
• Other Study ID Numbers: D0570C00005; 2008-004448-35