A Study to Investigate the Effect of Inhaling Single Doses of Different Formulations of GW642444M in Asthmatic Patients

NCT00702910 | Completed Phase 1

• 1 other identifier: B2C111401
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

Brief Summary

This study will involve the use of a new medicine called GW642444 being developed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The purpose of the study is to see how safe and how well tolerated the study drug is when inhaled in two different formulations as a fine powder by asthmatic patients. In addition, the study is designed to examine the effect of the study drug on the lungs, how the study drug affects parts of the body other than the lungs and to see how the body affects the study drug when it is given in single doses.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Asthma patients; Magnesium stearate; Tolerability; Safety; Lactose; GW642444M; Pharmacodynamics; Efficacy; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Mean change from baseline (pre-dose) FEV1 in trough (mean of the FEV1 values obtained 23 and 24 hours after dosing) FEV1

  on going

Secondary Outcomes (11)

• Mean change from baseline (pre-dose) in FEV1 (i.e. derive separate responses for each FEV1 obtained over 24 hours after dosing).

  on going

• General safety and tolerability, including adverse events, laboratory safety tests (haematology, clinical chemistry and urinalysis), vital signs and, 12-lead ECG.

  on going

• Weighted mean and maximum value (0 - 4 h) QTc(B)

  on going

• Weighted mean and maximum value (0 - 4 h) QTc(F)

  on going

• Weighted mean and maximum value (0 - 4 h) supine heart rate

  on going

Study Arms (3)

GW642444M/lactose

EXPERIMENTAL

GW642444M/lactose 6.25, 25 and 100 microgram, single inhaled dose for two days treatment in each treatment sequence (crossover design)

Drug: Placebo; Drug: GW642444; Drug: Magnesium Stearate

GW642444M/MgSt

EXPERIMENTAL

GW642444M/MgSt 6.25, 25 and 100 microgram, single inhaled dose for two days treatment in each treatment sequence (crossover design)

Drug: Placebo; Drug: GW642444; Drug: Magnesium Stearate

Placebo

PLACEBO COMPARATOR

Placebo containing lactose, single inhaled dose for two days treatment in each treatment sequence (crossover design)

Drug: Placebo; Drug: GW642444; Drug: Magnesium Stearate

Interventions

Placebo DRUG

comparator

GW642444M/MgSt; GW642444M/lactose; Placebo

GW642444 DRUG

investigational drug or placebo

Also known as: Placebo

GW642444M/MgSt; GW642444M/lactose; Placebo

Magnesium Stearate DRUG

Magnesium Stearate

GW642444M/MgSt; GW642444M/lactose; Placebo

Eligibility Criteria

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

You may qualify if:

• Male subjects or female subjects aged between 18 to 70 years.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\< 140 pmol/L) is confirmatory.
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 2 days post last-dose.
• Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of ≤ 10 pack years.
• Subjects with clinically stable, mild to moderate persistent asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 ≥ 60 % predicted as defined in the GINA guidelines \[Global Initiative for Asthma (GINA), 2006\] (having abstained from bronchodilators for the required period). Predicted values are based on the ECCS 1993 normal ranges.
• Body weight ≥ 50 kg and body mass index (BMI) within the range 19 - 29.9 kg/m2
• During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of ≥ 12.0% over baseline and an absolute change of ≥ 200 mL within 30 minutes following a single 400 mcg salbutamol dose.
• ECG criteria as per protocol
• Subjects who are currently taking ICS at a total daily dose of 200 to 500 mcg of FP or equivalent ICS.
• Subjects who are able and willing to give written informed consent to take part in the study.

You may not qualify if:

• Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, which may affect the safety of the subject or outcome of this study.
• A screening Holter ECG tracing that reveals clinically concerning arrhythmias.
• Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit
• Subjects with a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with either respiratory arrest or hypoxic seizures.
• Asthma exacerbations requiring treatment with oral corticosteroids: any exacerbations within 3 months of the screening visit or two or more exacerbations within 6 months of the screening visit or admittance to hospital for an asthma exacerbation within 1 year of the screening visit.
• Subjects classified as suffering from severe asthma as defined by the ATS guidelines
• Subjects who have taken high doses of an inhaled corticosteroid (\> 500 mcg FP/day or equivalent) within 8 weeks of the screening visit or oral steroids within 12 weeks of the screening visit.
• Subjects who have changed their inhaled corticosteroid treatment within the last 6 weeks before screening or can be expected to do so during the study.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four NCE's within 12 months prior to the first dosing day
• Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GW642444 inhalation powder (e.g., lactose, milk protein, magnesium stearate).
• Subjects with a positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or HIV result (if tested as per site SOPs) within 3 months of the start of the study.
• Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject's proper completion of the protocol requirements, including compliance.
• Abuse of alcohol is defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females).
• unit is equivalent to a half pint (220 mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Auchenflower, Queensland, 4066, Australia

Location

GSK Investigational Site

Clayton, Victoria, 3168, Australia

Location

GSK Investigational Site

Wellington, 6035, New Zealand

Location

Related Publications (1)

• Kempsford R, Norris V, Siederer S. Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther. 2013 Apr;26(2):256-64. doi: 10.1016/j.pupt.2012.12.001. Epub 2012 Dec 8.

  PMID: 23232038 BACKGROUND

Related Links

• Results for study B2C111401 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

stearic acid

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 18, 2008
• First Posted: June 20, 2008
• Study Start: April 27, 2008
• Primary Completion: October 4, 2008
• Study Completion: October 4, 2008
• Last Updated: August 10, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); NZ (1)