A study to test the efficacy and safety of GSK2269557 given in addition to regular health care in adult patients with an acute exacerbation of COPD

Phase 1

• Conditions: Chronic Obstructive Pulmonary Disease; MedDRA version: 18.1Level: LLTClassification code 10010953Term: COPD exacerbationSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-001972-70-NL
• Lead Sponsor: GlaxoSmithKline Reasearch & Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-01
• Last Update Posted: 30 May 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1) AGE
-Between 40 and 80 years of age inclusive, at the time of signing the informed consent.

2) TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
-The subject has a confirmed and established diagnosis of COPD, as defined by the GOLD guidelines for at least 6 months prior to entry.
-The subject has a post-bronchodilator FEV1/FVC < 0.7 and FEV1 = 80 % of predicted, documented in the last 5 years.
-Disease severity: Acute exacerbation of COPD requiring an escalation in therapy to include corticosteroid and antibiotics. Acute exacerbation to be confirmed by an experienced physician and represent a recent change in at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms.

Major symptoms:
- Subjective increase in dyspnea
- Increase in sputum volume
- Change in sputum colour

Minor symptoms:
- Cough
- Wheeze
- Sore throat

The subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years.
3) WEIGHT
- Body weight >or= 45 kg and body mass index (BMI) within the range 18 – 32 kg/m2

4) SEX
-Male
-Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:

1. Non-reproductive potential defined as:
-Pre-menopausal females with one of the following:
-Documented tubal ligation
-Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
-Hysterectomy
-Documented Bilateral Oophorectomy
-Postmenopausal defined as 12 months of spontaneous amenorrhea. Females whose
menopausal status is in doubt will be required to use, or have been using, one of the highly effective contraception methods as specified below from 30 days prior to the first dose of study medication and until completion of the follow-up visit.

2. Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit.
GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP)
This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penilevaginal intercourse on a long term and persistent basis.
1. Contraceptive subdermal implant that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label
2. Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label
3. Oral Contraceptive, either combined or progestogen alone
4. Injectable progestogen
5. Contraceptive vaginal ring
6. Percutaneous contraceptive patches
7. Male partner sterilization with documentation of azoospermia prior to the female subject’s entry into the study, and this male is the sole partner for that subject.
8. Male condom combined with a vaginal spermicide.
These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how t

Exclusion Criteria

1) CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER
FUNCTION AND QTC INTERVAL)
To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study:
-Need for invasive mechanical ventilation (short term (< 48h) NIV or CPAP is acceptable)
-Haemodynamic instability or clinically significant heart failure
-Confusion
- Clinically significant pneumonia, identified by chest X-ray (if available) or on the CT scan performed during screening, as judged by the Investigator and in consultation with the GSK Medical Monitor, if required. (NOTE: Since CT is more sensitive than X-ray for detecting pneumonia, minor patches of infection or
bronchopneumonia seen on CT at screening are expected and therefore allowed.)
-Subjects who have a history or current medical conditions or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or NIDDM) are permitted to be entered into the study).
-Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt
bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results.
-ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin <35%).
-A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the exclusion criteria, outside of the reference range for the population being studied may be included if the Investigator [in consultation with the
GSK Medical Monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
-Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
- ECG indicative of an acute cardiac event (e.g. Myocardial Infarction) or demonstrating a clinically significant arrhythmia requiring treatment.
-QTcF > 450 msec or QTcF > 480 msec in subjects with Bundle Branch Block, based on single QTcF value.
-Subjects who have undergone lung volume reduction surgery.

20 CONCOMITANT MEDICATIONS
-Subject is currently on chronic treatment with macrolides; long term oxygen therapy (> 15 hours/day).
-The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti-
TNF), anti-Interleukin-1 (anti-IL1), or any other immunosuppressive therapy within
60 days prior to dosing.

3) RELEVANT HABITS
-History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

4) CONTRAINDICATIONS
-History of sensitivity to any of the study medications, or components thereof (such as lactose) or a history of drug or other allergy that, in the opinion of the investigator or
Medical Monitor, contraindicates their participation.

5) DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
-A known (historical) positive

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified