Two-part Pharmacokinetic and Pharmacodynamic Study of LAS190792 in Patients With Asthma and COPD

Phase 1

Completed

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); Asthma
• Interventions: Drug: LAS190792 Dose 1; Drug: LAS190792 Dose 2; Drug: Placebo; Drug: LAS190792 Dose 2 (Part 2); Drug: LAS190792 Dose 5; Drug: Tiotropium 18 μg; Drug: Indacaterol 150 μg; Drug: LAS190792 Dose 3; Drug: LAS190792 Dose 4; Drug: LAS190792 Dose 6; Drug: LAS190792 Dose 1 (Part 2)

• Registration Number: NCT02059434
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to assess the safety and tolerability of single doses of LAS190792 administered by inhalation to patients with mild persistent asthma and moderate to severe chronic obstructive pulmonary disease (COPD) and also to assess the ability of LAS190792 to produce bronchodilation (opening of the airways).

Detailed Description

This study is an integrated Phase I protocol divided into 2 parts.

Part one: a single ascending dose study (6 LAS190792 dose levels) in 16 male subjects with mild asthma. LAS190792 will be administered (by the Genuair® inhaler) under supervision at the study centre, according to the randomisation scheme. One dose level will be administered per week with 2 to 3 weeks between each dose level for the safety and pharmacokinetic data review.

Part two: A 5-way , crossover, single dose study (of LAS190792 \[two doses\], indacaterol, tiotropium and placebo) in 40 male and non-childbearing potential women subjects with moderate to severe COPD. Each treatment period will be separated by a washout period of at least 7 to 14 days. The aim is to ensure at least 30 subjects complete Part 2 of the study. The primary comparison for bronchodilation will be between LAS190792 doses and placebo. Other treatment comparisons (indacaterol or tiotropium vs placebo and LAS190792 vs indacaterol or tiotropium) will be considered additional.

Study Timeline

• Study Start: 2013-09-01
• Study First Submitted: 2014-02-07
• Study First Submitted QC: 2014-02-07
• Study First Posted: 2014-02-11
• Primary Completion: 2014-10-06
• Study Completion: 2014-10-06
• Results First Submitted: 2016-12-30
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-26
• Last Update Submitted: 2019-03-26
• Results First Posted: 2019-06-21
• Last Update Posted: 2019-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LAS190792 Dose 1 (Part 1)	LAS190792 Dose 1	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 2 (Part 1)	LAS190792 Dose 2	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
Placebo (Part 1)	Placebo	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 2 (Part 2)	LAS190792 Dose 2 (Part 2)	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 5 (Part 1)	LAS190792 Dose 5	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
Placebo (Part 2)	Placebo	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
Tiotropium 18 μg	Tiotropium 18 μg	Single dose, oral inhalation by HandiHaler® single-dose DPI
Indacaterol 150 μg	Indacaterol 150 μg	Single dose, oral inhalation by Breezhaler® single-dose DPI
LAS190792 Dose 3 (Part 1)	LAS190792 Dose 3	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 4 (Part 1)	LAS190792 Dose 4	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 6 (Part 1)	LAS190792 Dose 6	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
LAS190792 Dose 1 (Part 2)	LAS190792 Dose 1 (Part 2)	Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Primary Outcome Measures

Name	Time	Method
Subjects With ≥1 Treatment-emergent Adverse Event	30 Days	Adverse events (AEs) are any unfavorable and unintended medical occurrence during the subject's participation in the study (including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, an ECG abnormality, a 12-lead 24-hour ECG-Holter abnormality, a blood pressure abnormal value, paradoxal bronchospasm or an abnormal finding in the physical examination) and will be coded using the current Medical Dictionary for Regulatory Activities (MedDRA).
Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second)	Day 2	Trough is defined as the mean of the FEV1 values obtained at 23 hours and at 24 hours after morning investigational product administration.

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	Up to 36 hours after investigational product administration
Time to Maximum Observed Plasma Concentration (Tmax)	Up to 36 hours after investigational product administration
Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration	Up to 36 hours after investigational product administration

Trial Locations

Locations (2)

Medicines Evaluation Unit Ltd (MEU); 🇬🇧 Manchester, United Kingdom

Quintiles Drug Research Unit at Guy's Hospital; 🇬🇧 London, United Kingdom