Dose-Ranging Study Of GSK233705B In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: Placebo; Drug: GSK233705 200mcg; Drug: GSK233705 12.5mcg; Drug: GSK233705 25mcg; Drug: GSK233705 50mcg; Drug: GSK233705 100mcg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00676052

AC2110664

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of GSK233705B compared with placebo in subjects with COPD.

Enrollment: 576 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• A signed and dated written informed consent prior to study participation.
• Male or female adults.

A female is eligible to enter and participate in this study if she is of:

non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal; or child-bearing potential, has a negative pregnancy test at Visit 1/Visit 1A, and agrees to one of the protocol-specified acceptable contraceptive methods used consistently and correctly (i.e. according to the approved product label and the instructions of the physician for the duration of the study - Screening through follow-up contact)

• 40 to 80 years of age at Visit 1
• An established clinical history of COPD
• Current or previous cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years 1.
• A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a post-albuterol/salbutamol FEV1 of ≥35 and ≤70% of predicted normal values

Exclusion criteria

Subjects meeting any of the following criteria must not be enrolled in the study:

• Women who are pregnant or lactating.
• A current diagnosis of asthma.
• Known respiratory disorders other than COPD including but not limited to α-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease.
• Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy)
• Clinically significant Chest X-ray or computed tomography (CT) scan abnormalities within 6 months prior to Visit 1 that are not believed to be due to COPD.
• Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.
• Hospitalization for COPD or pneumonia within 3 months prior to Visit 1.
• Use of antibiotics for a lower respiratory tract infection within 30 days prior to Visit 1.
• Clinically significant and uncontrolled cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities.
• An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in active medical problem.
• Positive for Hepatitis B or Hepatitis C at Visit 1.
• A current malignancy or previous history of cancer in remission for <5 years prior to Visit 1
• A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and any of their derivatives, lactose/milk protein or magnesium stearate.
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholingeric.
• Medically unable to withhold albuterol/salbutamol for 6 hours prior to spirometry testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour period prior to the first 3 study visits (ipratropium cannot be used after Visit 3).
• Additional Medications: Unable to stop using certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)
• Use of inhaled corticosteroids at a dose greater than 1000 mcg/day of fluticasone propionate or equivalent within 30 days prior to Visit 1.
• Use of long-term oxygen therapy (LTOT) or supplemental oxygen required for greater than 12 hours a day. Oxygen use as needed is not exclusionary.
• Clinically significant sleep apnea that requires continuous positive airway pressure (CPAP)
• Use of regular nebulized therapy
• Use of nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV)
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1.
• An investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the above who is involved in this study
• History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse in the two years prior to Visit 1 (including drug and alcohol), or other conditions, which will limit the validity of informed consent to participate in the study.
• Use of GSK233705B in previous studies.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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576 participants in 6 patient groups, including a placebo group

Arm 1

Experimental group

Description:

GSK233705 12.5mcg

Treatment:

Drug: GSK233705 12.5mcg

Arm 2

Experimental group

Description:

GSK233705 25mcg

Treatment:

Drug: GSK233705 25mcg

Arm 3

Experimental group

Description:

GSK233705 50mcg

Treatment:

Drug: GSK233705 50mcg

Arm 4

Experimental group

Description:

GSK233705 100mcg

Treatment:

Drug: GSK233705 100mcg

Arm 5

Experimental group

Description:

GSK233705 200mcg

Treatment:

Drug: GSK233705 200mcg

Arm 6

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo