A 2 Part Study Examining Doses Of GSK961081 In Healthy Volunteers And Then In COPD Patients

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00478738
First received: May 24, 2007
Last updated: March 10, 2011
Last verified: March 2011
  Purpose

GSK961081 has previously been administered to healthy subjects in a nebulised formulation and the first part of this study which will be conducted in healthy subjects proposes to bridge the change from nebulised to DPI formulation of GSK961081 before administration to patients. The second part of the study will be conducted in COPD patients and aims to assess the safety and bronchodilator profile of GSK961081 over 24 hours, during 14 days dosing.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Healthy Subjects
Chronic Obstructive Airway Disease
Drug: GSK961081
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: See Detailed Description

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To assess systemic pharmacokinetics of GSK961081 DPI after single inhaled doses in healthy male subjects and then to investigate the pulmonary pharmacodynamic profile(FEV1) of 2 doses versus placebo at 14 days in patients with COPD [ Time Frame: at 14 days ]

Secondary Outcome Measures:
  • To investigate the safety and tolerability (HR, BP, Potassium, Glucose) of GSK961081 and to investigate the pharmacokinetic and systemic pharmacodynamic profile(sGAW) of GSK961081 at 14 days. [ Time Frame: at 14 days ]
  • ·Adverse events, clinical laboratory safety tests, cardiac monitoring, ambulatory blood pressure, vital signs (including postural changes in blood pressure),
  • 12-lead ECG parameters including QTc(b) and QTc(f), rescue medication usage, blood glucose and serum potassium
  • ·The following endpoints will be derived for the supine systolic blood pressure, change from baseline supine heart rate, change from baseline QTc(F) and change from baseline QTc(B).
  • - Maximum value (0-4 h)
  • - Weighted mean (0-4 h)
  • ·The following endpoints will be derived for the supine diastolic blood pressure.
  • - Minimum value (0-4h)
  • - Weighted mean (0-4h)
  • ·The following endpoints will be derived for the systolic and diastolic postural change in blood pressure
  • - Maximum value (0-4h)
  • ·The following endpoints will be derived for serum potassium.
  • - Maximum decrease from baseline value (0-4h).
  • -Weighted mean change from baseline (0-4h).
  • ·Ambulatory blood pressure: maximum, minimum, time to maximum, time to minimum and weighted mean for systolic and diastolic blood pressure, and weighted mean arterial pressure over 0-8 and 8-24 h after dosing on Days 1 and 14
  • ·Holter monitoring: maximum, minimum and mean HR, normal and aberrant beats, number of supraventricular contractions,
  • premature atrial contractions, premature ventricular contractions, couplets, triplets, ventricular runs and ventricular tachycardias on Days 1 and 14.
  • ·sGAW measurement over 24 hours post-dose on Days 1 and 14
  • ·Plasma concentrations of GSK961081 and derived pharmacokinetic parameters

Estimated Enrollment: 40
Study Start Date: June 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GSK961081
    Other Name: GSK961081
Detailed Description:

A study to assess the pharmacokinetics of single escalating doses of inhaled GSK961081 DPI (a dual pharmacophore) in healthy subjects (Part 1) and a randomised, double-blind, double dummy, crossover (incomplete block) study to assess the safety, tolerability, pharmacodynamics (pulmonary and systemic) and pharmacokinetics of 14 days dosing with inhaled GSK961081 DPI compared with placebo and tiotropium plus salmeterol in patients with COPD (Part 2).

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 ie 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 (stage II) in accordance with ATS/ERS guidelines (see Appendix 2: COPD Guidelines).
  • 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 ipratropium bromide defined as:

Either an increase in FEV1 of > 12 % and > 150 mLwithin 2 hour following inhalation of 80 µcg ipratropium bromide at the screening visit Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hour following inhalation of 80 µcg ipratropium bromide within 6 months of screening and an increase in FEV1 of > 6 % and > 100 mL within 2 h following inhalation of 80 mg ipratropium bromide 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 hour following inhalation of 400 mg salbutamol at the screening visit Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hour following inhalation of 400 mg salbutamol within 6 months of screening and an increase in FEV1 of > 6 % and >100 mL within 2 h following inhalation of 400 mg salbutamol 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 within the range 18-35 kilograms/metre² (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 measurements

Exclusion Criteria:

  • 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
  • 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 drug screen. A minimum list of drugs that will be screened for include Amphetamines, barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
  • The subject has a positive alcohol test (breath or urine) predose.
  • 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 a 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 or intends to donate within 56 days after completing the study.
  • The subject has claustrophobia that may be aggravated by entering the plethysmography cabinet.
  • Subject has an FEV1 < 50 % 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, salbutamol, tiotropium, salmeterol or lactose
  • A subject in whom ipratropium, salbutamol, tiotropium and/or salmeterol is contraindicated
  • Subjects with lung volume reduction surgery within 12 months of screening
  • Poorly controlled COPD defined as:

Either: acute worsening of COPD that is managed by the subject at home by treatment with increased corticosteroids or antibiotics in the 6 weeks before screening Or: more than 2 exacerbations in the previous 12 months before screening that required a course of oral steroids or antibiotics, and/or required hospitalisation

  • Subject has had a respiratory tract infection in the 4 weeks before screening
  • Subject requires treatment with inhaled cromolyn sodium, theophyline, oral beta agonists, nebulised anticholinergics or leukotriene antagonists
  • Subject is unable to abstain from long acting beta agonist from 72 hours before screening and throughout the dosing period
  • Subject is unable to abstain from tiotropium from 28 days before screening and throughout the dosing period
  • Subject is predicted to be unable to abstain from short acting inhaled beta agonists (to be used as rescue medication during the study) for 6 hours before screening and before study visits, when required, until all post dose lung function tests have been completed for a given study day.
  • Subject has received oral corticosteroids within the 6 weeks before screening
  • Subject is receiving > 1000 mg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or is predicted not to be able to maintain a constant dose during the study
  • Subject is receiving oxygen therapy or nocturnal positive pressure treatment
  • Subject has prostate hypertrophy or narrow angle glaucoma
  • The subject is unable to use the dosing devices correctly.
  • Subject with carcinoma that has not been in complete remission for at least 5 years (with the exception of carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma if the subject is considered cured)
  • A history of congestive heart failure, coronary insufficiency or cardiac arrhythmia
  • Abnormal 12- lead ECG abnormality which is either clinically significant or may interfere with QTc measurement
  • A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
  • Elevated supine blood pressure higher than 160/95 at screening.
  • Subject is receiving a diuretic and/ or beta adrenergic antagonist.
  • Subject has a serum potassium level below the reference range at screening.
  • Strict vegetarians;
  • Shift-worker unable to comply with the study;
  • Inability to understand the protocol requirements, instructions and study-related restrictions; the nature, scope and possible consequences of the study;
  • Unlikely to complete the study; e.g., uncooperative attitude, inability to return for Follow-up Visits;
  • Subject is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the study;
  • Vulnerable individuals (e.g., persons kept in detention).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478738

Locations
Germany
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Berlin, Germany, 14050
South Africa
GSK Investigational Site
Bloemfontein, South Africa, 9301
GSK Investigational Site
George, South Africa, 6530
GSK Investigational Site
Mowbray, South Africa, 7700
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD MDsc FFPM GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00478738     History of Changes
Other Study ID Numbers: MAB104958
Study First Received: May 24, 2007
Last Updated: March 10, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GlaxoSmithKline:
b-agonist,
COPD.
pharmacodynamic,
pharmacokinetic,
anti muscarinic,

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 22, 2014