A Study To Assess Single Dosage Strength Of GW685698/GW642444 Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: GW685698/GW642444
Intervention description: GW685698/GW642444
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 60.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; Novel Dry Powder Inhaler; Chronic Obstructive Pulmonary Disease (COPD); GW685698/GW642444

Summary:

      The purpose of this study is to assess the safety and efficacy of a single dosage strength of
      GW685698/GW642444 in subjects with Chronic Obstructive Pulmonary Disease (COPD).
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible for enrollment in the study must meet all of the following criteria:

          1. Informed consent: Subjects must give their signed written informed consent to
             participate.

          2. Gender: Male subjects or female subjects of non-child bearing potential (e.g.
             post-menopausal or surgical sterile) 40 - 80 years of age at screening (Visit 1).

               -  Post-menopausal females are defined as being amenorrhoeic for greater than 2
                  years with an appropriate clinical profile, e.g. age appropriate, history of
                  vasomotor symptoms. However if indicated this can be confirmed by estradiol and
                  FSH levels consistent with menopause (according to laboratory ranges) at
                  screening (Visit 1).

               -  Surgically sterile females are defined as those with a documented (medical report
                  verification) hysterectomy and/or bilateral oophorectomy or Tubal Ligation.

               -  Furthermore, male subjects in this study must use double-barrier
                  (condom/spermicide) birth control methods or abstain from sexual intercourse with
                  female partners who are pregnant, lactating, or able to bear children in addition
                  to any birth control methods the female partner is using, from the first dose of
                  the study medication until 90 days after the last dose of the study medication.

          3. COPD diagnosis: Subjects with a clinical history of COPD in accordance with the
             following definition by the American Thoracic Society/European Respiratory Society
             [Celli, 2004] :

             COPD is a preventable and treatable disease characterized by airflow limitation that
             is not fully reversible. The airflow limitation is usually progressive and is
             associated with an abnormal inflammatory response of the lungs to noxious particles or
             gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also
             produces significant systemic consequences.

          4. Tobacco use: subjects with a current or previous history of ≥ 10 pack-years of
             cigarette smoking at screening (Visit 1). Previous smokers are defined as those who
             have stopped smoking for at least 6 months prior to Visit 1.

             • Number of pack years = (number of cigarette per day/20)) x number of years smoked

          5. Severity of Disease: subjects who conform to the current severity classification for
             Stage II/III disease in terms of post-bronchodilator spirometry at Screening Visit 1:

               -  Subject with a measured post-salbutamol FEV1/FVC ratio of ≤0.70

               -  Subjects with a measured post-salbutamol FEV1 ≥ 40 % and ≤ 80 % of predicted
                  normal values calculated using NHANES III reference equations.

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

          1. Pregnancy: Women who are pregnant or lactating

          2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
             asthma are eligible if COPD is the current diagnosis)

          3. α1- antitrypsin deficiency: Subjects with α-1 antitrypsin deficiency as the underlying
             cause of COPD

          4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
             bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung
             diseases or other active pulmonary diseases

          5. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior
             to Screening

          6. Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals
             evidence of clinically significant abnormalities not believed to be due to the
             presence of COPD. A chest X-ray must be taken at Screening if a chest X-ray or CT scan
             is not available within 6 months prior to Screening

          7. Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the
             occurrence of any of the following in the 6 weeks prior to Screening:

               -  Acute worsening of COPD that is managed by subject with corticosteroids or
                  antibiotics, or

               -  Acute worsening of COPD that requires treatment prescribed by a physician
                  Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of
                  the Screening Visit

          8. Lower respiratory tract infection: Subjects with lower respiratory tract infection
             that required the use of antibiotics within 6 weeks prior to Visit 1

          9. 12-lead ECG (Electrocardiogram): An abnormal and clinically significant 12-lead ECG
             that results in an active medical problem. For this study, an abnormal ECG is defined
             as a 12-lead tracing that is interpreted as, but not limited to, any of the following:

               -  Clinically significant conduction abnormalities (e.g. left bundle branch block,
                  Wolff-Parkinson-White syndrome)

               -  Clinically significant arrhythmias (e.g. atrial fibrillation, ventricular
                  tachycardia)

             The independent cardiologist, contracted by GSK, will determine the clinical
             significance of any ECG abnormalities and determine if a subject is precluded from
             entering the study. However, the following predetermined ECG abnormalities are
             considered clinically significant and will result in exclusion of a subject:

               -  Ventricular rate < 45 bpm

               -  PR interval > 240 msec

               -  Evidence of Second-Degree (Mobitz type II) or Third-Degree atrioventricular (AV)
                  block

               -  Pathological Q waves

               -  Non-specific intraventricular conduction delay

               -  ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities)

               -  Right or left complete bundle branch block

               -  A mean QTc(B) value at Screening > 450 msec, or uncorrected QT >600 msec or an
                  ECG that is not suitable for QT measurements (e.g. poorly defined termination of
                  the T wave)

         10. Other Diseases/abnormalities: Subjects with historical or current evidence of
             clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
             immunological, endocrine (including uncontrolled diabetes or thyroid disease) or
             haematological abnormalities that are uncontrolled. Significant is defined as any
             disease that, in the opinion of the investigator, would put the safety of the subject
             at risk through participation, or which would affect the efficacy or safety analysis
             if the disease/condition exacerbated during the study.

         11. Hepatitis: Subjects with a positive Hepatitis B surface antigen or positive Hepatitis
             C antibody pre-study or at Screening

         12. Hypertension: Subjects with clinically significant hypertension that is uncontrolled

         13. Cancer: Subjects with carcinoma that has not been in complete remission for at least 5
             years.

             • Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of
             the skin would not be excluded if the subject has been considered cured within 5 years
             since diagnosis.

         14. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
             medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
             powder (e.g. lactose, magnesium stearate). Or a history of drug or other allergy such
             as a history of severe milk protein allergy that, in the opinion of the study
             physician, contraindicates the subject's participation

         15. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
             abuse within the last 2 years

         16. Medication prior to spirometry: Subjects who are medically unable to withhold their
             rescue medication for the 6-hour period required prior to spirometry testing at each
             study visit.

         17. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or
             nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use
             (i.e. ≤ 12 hours per day) is not exclusionary.

         18. Pulmonary rehabilitation: Subjects who have participated in the acute phase of a
             Pulmonary Rehabilitation Programme within 4 weeks prior to Screening or who will enter
             the acute phase of a Pulmonary Rehabilitation Programme during the study. Subjects who
             are in the maintenance phase of a Pulmonary Rehabilitation Programme may be included.

         19. Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study
             procedures

         20. Questionable validity of Consent: Subjects with a history of psychiatric disease,
             intellectual deficiency, poor motivation or other conditions that will limit the
             validity of informed consent to participate in the study

         21. Prior use of study medication/other investigational drugs: Subjects who have received
             the GW642444 in previous studies. Subjects who have received an investigational drug
             within 30 days of entry into this study (Screening), or within 5 drug half-lives of
             the investigational drug, whichever is longer

         22. Sleep apnea: Subjects with clinically significant sleep apnea that is uncontrolled.

         23. Affiliation with investigator site: Study investigators, sub-investigators, study
             coordinators, employees of a participating investigator or immediate family members of
             the aforementioned are excluded from participating in this study