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

NCT02059434 | Completed Phase 1 Results

• 2 other identifiers: M-190792-012013-001758-93
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

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).

Conditions

Chronic Obstructive Pulmonary Disease (COPD); Asthma

Outcome Measures

Primary Outcomes (2)

• Subjects With ≥1 Treatment-emergent Adverse Event

  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).

  30 Days

• Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second)

  Trough is defined as the mean of the FEV1 values obtained at 23 hours and at 24 hours after morning investigational product administration.

  Day 2

Secondary Outcomes (3)

• 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

Study Arms (12)

LAS190792 Dose 1 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 1

LAS190792 Dose 2 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 2

LAS190792 Dose 3 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 3

LAS190792 Dose 4 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 4

LAS190792 Dose 5 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 5

LAS190792 Dose 6 (Part 1)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 6

Placebo (Part 1)

PLACEBO COMPARATOR

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: Placebo

LAS190792 Dose 1 (Part 2)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 1 (Part 2)

LAS190792 Dose 2 (Part 2)

EXPERIMENTAL

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: LAS190792 Dose 2 (Part 2)

Tiotropium 18 μg

ACTIVE COMPARATOR

Single dose, oral inhalation by HandiHaler® single-dose DPI

Drug: Tiotropium 18 μg

Indacaterol 150 μg

ACTIVE COMPARATOR

Single dose, oral inhalation by Breezhaler® single-dose DPI

Drug: Indacaterol 150 μg

Placebo (Part 2)

PLACEBO COMPARATOR

Single dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

Drug: Placebo

Interventions

LAS190792 Dose 1 DRUG

LAS190792 Dose 1 (Part 1)

LAS190792 Dose 2 DRUG

LAS190792 Dose 2 (Part 1)

LAS190792 Dose 3 DRUG

LAS190792 Dose 3 (Part 1)

LAS190792 Dose 4 DRUG

LAS190792 Dose 4 (Part 1)

LAS190792 Dose 5 DRUG

LAS190792 Dose 5 (Part 1)

LAS190792 Dose 6 DRUG

LAS190792 Dose 6 (Part 1)

LAS190792 Dose 1 (Part 2) DRUG

LAS190792 Dose 1 (Part 2)

LAS190792 Dose 2 (Part 2) DRUG

LAS190792 Dose 2 (Part 2)

Tiotropium 18 μg DRUG

Also known as: Spiriva

Tiotropium 18 μg

Indacaterol 150 μg DRUG

Also known as: Onbrez

Indacaterol 150 μg

Placebo DRUG

Placebo (Part 1); Placebo (Part 2)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male subjects aged 18 to 70 years
• Body mass index (BMI) 18.5 to 30 kg/m2 at screening
• Clinical diagnosis of mild persistent asthma (according to GINA guidelines) for at least 6 months prior to screening
• Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods
• Screening FEV1 value of ≥70% of the predicted normal value after a washout of at least 5 h for short-acting beta2-agonists and 72 h for long-acting beta2-agonists
• FEV1 reversibility of ≥12% and an absolute increase of at least 200 mL over the baseline value within 30 min after inhalation of 400 µg of salbutamol
• Subjects using intermittent salbutamol and / or subjects on a stable dose or regimen of low dose ICS (as defined by the GINA guidelines) at least 4 weeks prior to screening
• Predose FEV1 value of first treatment period within the range of ±20% of the FEV1 measured at screening prior to salbutamol inhalation
• Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings
• Normal blood pressure (defined as SBP between 100 and 140 mmHg, and DBP between 50 and 90 mmHg) at screening, measured after resting in supine position for 5 minutes.
• Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator
• Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody (IgM), hepatitis C antibody and human immunodeficiency virus (HIV) I and II antibodies at screening
• Subjects who are able and willing to provide written informed consent
• Subjects able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005 criteria at screening
• Adult male and non-childbearing potential women subjects aged ≥40 years with a clinical diagnosis of stable moderate to severe COPD according to GOLD guidelines at screening

You may not qualify if:

• Current smokers, subjects with a smoking history during the last 12 months or subjects with a smoking history of more than 10 pack-years
• Other relevant pulmonary disease or history of thoracic surgery
• Subjects with a BMI ≥40 kg/m2 (only applicable for Part 2)
• Subjects with any clinically relevant history or presence of abnormality from the medical history and/or physical examination (only applicable for Part 1)
• Current evidence or recent history of any clinically significant and unstable disease (other than COPD) or abnormality that could put the subject at risk or could confound the results of the study (only applicable for Part 2)
• Subjects with a surgical history clinically relevant for the purpose of the study
• History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin
• Subjects with serious adverse reaction or serious hypersensitivity to Spiriva (for Part 2 only), indacaterol (for Part 2 only), or the formulation excipients (eg, lactose) or other drugs in the same pharmacologic class (for Part 1 and Part 2)
• Current diagnosis of COPD (for Part 1 only) or history of / or current diagnosis for asthma (for Part 2 only)
• Recent history of asthma / COPD exacerbation requiring hospitalisation or need for increased maintenance treatments for asthma / COPD within 6 weeks prior to screening or randomisation
• Use of daily oxygen therapy \>10 h per day (for Part 2 only)
• Use of systemic steroids for respiratory reasons within 3 months prior to screening
• Lower respiratory tract infection within 6 weeks prior to screening or randomisation
• Upper respiratory tract infection requiring antibiotics within 4 weeks prior to screening or randomisation
• Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Quintiles Drug Research Unit at Guy's Hospital

London, SE1 1YR, United Kingdom

Location

Medicines Evaluation Unit Ltd (MEU)

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

Interventions

Tiotropium Bromide; indacaterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Limitations and Caveats

In Part 1, many plasma concentrations at 50-100µg dose levels were BLOQ; thus only limited PK data were obtained for AUC(0-t), with plasma concentrations generally detected up to 1h post-administration; and at 200-400µg, up to 6 or 12h, respectively

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 11, 2014
• Study Start: September 1, 2013
• Primary Completion: October 6, 2014
• Study Completion: October 6, 2014
• Last Updated: June 21, 2019
• Results First Posted: June 21, 2019

Record last verified: 2019-03

Locations

GB (2)