An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.

NCT00674817 | Completed Phase 2 Results

• 1 other identifier: MAB110123
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 4

Brief Summary

GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

salbutamol,; Chronic Obstructive Pulmonary Disease (COPD); GSK961081 muscarinic receptor antagonist,; COPD; ipratropium bromide,; Asthma; ß2-adrenergic agonist,

Outcome Measures

Primary Outcomes (1)

• Maximal Change in Forced Expiratory Volume in One Second (FEV1) From Baseline (Pre-dose on Day 1) in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h,12h and 24h.

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.

  Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1

Secondary Outcomes (22)

• Maximal Change in Forced Vital Capacity (FVC) in One Second From Pre-dose in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h, 12h and 24h.

  Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1

• Number of Participants With Adverse Events and Serious Adverse Events

  Upto 82 days

• Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)

  Up to 42 days

• Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours

  Up to 27 hours post Day 1 dosing

• Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours

  Up to 27 hours post Day 1 dosing

Study Arms (6)

400 microgrammes GSK961081 and salbutamol

EXPERIMENTAL

400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.

Drug: 400 microgrammes GSK961081

1200 microgrammes GSK961081 and salbutamol

EXPERIMENTAL

1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.

Drug: 400 microgrammes GSK961081; Drug: 1200 microgrammes GSK961081

400 microgrammes GSK961081 and ipratropium bromide

EXPERIMENTAL

400 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Drug: 1200 microgrammes GSK961081

1200 microgrammes of GSK961081 and ipratropium bromide

EXPERIMENTAL

1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Drug: 400 microgrammes GSK961081; Drug: 1200 microgrammes GSK961081

400 microgrammes of GSK961081 and placebo

PLACEBO COMPARATOR

400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.

Drug: 1200 microgrammes GSK961081

1200 microgrammes of GSK961081 and placebo

PLACEBO COMPARATOR

1200 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.

Drug: 400 microgrammes GSK961081

Interventions

400 microgrammes GSK961081 DRUG

Inhaled GSK961081 administered via Dry Powder Inhaler.

1200 microgrammes GSK961081 and salbutamol; 1200 microgrammes of GSK961081 and ipratropium bromide; 1200 microgrammes of GSK961081 and placebo; 400 microgrammes GSK961081 and salbutamol

1200 microgrammes GSK961081 DRUG

Inhaled GSK961081 adminisntered via dry powder inhaler.

1200 microgrammes GSK961081 and salbutamol; 1200 microgrammes of GSK961081 and ipratropium bromide; 400 microgrammes GSK961081 and ipratropium bromide; 400 microgrammes of GSK961081 and placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is male or female (of non-child bearing potential) ≥ 40 years of age and ≤ 75 years of age.
• Non- child bearing potential is defined as physiologically incapable of becoming pregnant, including females who are post-menopausal (more than 2 years without menses with appropriate clinical history i.e. age, history of vasomotor symptoms-estradiol and FSH levels may be checked if indicated) and females who are surgically sterile (hysterectomy, tubal ligation or bilateral oophorectomy).
• Subject diagnosed with COPD in accordance with ATS/ERS guidelines (as per protocol).
• Subject is a smoker or an ex-smoker with a history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent)
• Subject has FEV1/FVC \< 0.7 post-bronchodilator (salbutamol)
• Subject has FEV1 \< 80 % of predicted normal for height, age, gender after inhalation of salbutamol
• Response to ipatropium bromide defined as:
• Either an increase in FEV1 of \> 12 % and \> 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit
• Or: a documented increase in FEV1 of \>12 % and \> 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide within 6 months of screening and an increase in FEV1 of \> 6 % and \> 100 mL within 2h following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit (in order to allow for potential fluctuations in the response to ipratropium bromide in patients known to be responders to ipratropium bromide)
• Response to salbutamol defined as:
• Either an increase in FEV1 of \> 12 % and \> 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit
• Or: a documented increase in FEV1 of \>12 % and \> 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI within 6 months of screening and an increase in FEV1 of \> 6 % and \>100 mL within 2h following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit (in order to allow for potential fluctuations in the response to salbutamol in patients known to be responders to salbutamol)
• Body mass index (BMI) within the range 18-35 kg/m2
• Subject is able and willing to give written informed consent to take part in the study.
• Subject is available to complete all study assessments

You may not qualify if:

• Subjects who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
• Subjects with clinically relevant findings on laboratory safety tests. Subjects with laboratory values outside the reference range may be include in the study if the Investigator and medical monitor agree that these findings would not put the subject at risk or interfere with the objectives of the study
• Women who are pregnant or lactating
• An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose
• The subject has a positive urine drugs of abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbituates, cocaine, opiates, cannabinoids and benzodiazepines.
• A history, or suspected history, of alcohol abuse within the 6 months before the screening visit.
• A positive test for hepatitis C antibody, hepatitis B surface antigen, or HIV.
• The subject has participated in a clinical study with another New Chemical Entity within the past 2 months or participated in a clinical study with any other drug during the previous month.
• The subject has donated a unit of blood within the 56 days of dosing or intends to donate within 56 days after completing the study.
• Subject has an FEV1 \< 40 % of predicted for age, height and gender after inhalation of salbutamol.
• The subject has a diagnosis of active tuberculosis, lung cancer, sarcoidosis, bronchiectasis, lung fibrosis, pulmonary hypertension or with a primary diagnosis of asthma
• The subject has a known allergy or hypersensitivity to ipratropium bromide, salbutamol, or lactose
• A subject in whom ipratropium bromide or salbutamol is contraindicated
• Subjects with lung volume reduction surgery within 12 months of screening
• Poorly controlled COPD defined as:

Sponsors & Collaborators

• Theravance Biopharma: lead
• GlaxoSmithKline: collaborator

Study Sites (4)

GSK Investigational Site

Wellington, 6035, New Zealand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

GSK Investigational Site

Khon Kaen, 40002, Thailand

Location

GSK Investigational Site

Manchester, M23 9LT, United Kingdom

Location

Related Publications (1)

• Norris V, Ambery C. Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD. Pulm Pharmacol Ther. 2013 Oct;26(5):574-80. doi: 10.1016/j.pupt.2013.03.009. Epub 2013 Mar 21.

  PMID: 23524017 BACKGROUND

Related Links

• 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; Asthma

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: May 8, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 19, 2008
• Last Updated: October 20, 2021
• Results First Posted: March 27, 2017

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

TH (2); NZ (1); GB (1)