Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2008RESP09
Study information
Scientific title
An investigation of the safety and efficacy of oral AKL1 in patients diagnosed with obstructive lung disease: a randomised, double blind, placebo-controlled parallel group study
Acronym
TAKL
Study hypothesis
AKL1 will improve cough in patients with obstructive airways disease.
Ethics approval
Cambridge 4 Research Ethics Committee approved on the 2nd February 2009 (ref: 08/H0305/54)
Study design
Placebo-controlled randomised parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please contact sundari.ampi@nnuh.nhs.uk or +44 (0)1603 289876 to request a patient information sheet
Condition
Obstructive airways disease
Intervention
Patients will be randomised at visit 2 (week 0) to receive either AKL1 or placebo for a total of 8 weeks duration. They will be asked to take two 500 mg capsules of AKL1/placebo at approximately the same time each morning between 07:00 am and 10:00 am and then repeated again between 19:00pm and 22:00 pm.
Visit 3 is 4 weeks later and is purely a safety visit to check for any adverse events or compliance issues.
Final visit 4 is 8 weeks from vist 2. If there are any unresolved adverse events a further follow-up visit will be scheduled.
Intervention type
Drug
Phase
Not Applicable
Drug names
AKL1
Primary outcome measure
Leicester Cough Questionnaire between baseline (week 0) and week 8
Secondary outcome measures
Change from baseline to week 8:
1. St George's Respiratory Questionnaire (SGRQ) score
2. European Quality of Life (EQ-5D) score
3. Spirometry (peak expiratory flow [PEF], FEV1, FVC, forced expiratory flow [FEF] 25 - 75 as percent predicted)
4. Forced Oscillation Technique
5. Differential spontaneous sputum cell count; tumour necrotising factor alpha (TNFa), interleukin-8 (IL-8), interleukin-10 (IL-10) concentration
6. Modified Medical Research Council (MRC) dyspnoea score
7. Six-minute walk test
8. Oxygen saturation (O2 Sats) (pre- and post-six-minute walk test)
There will also be exploratory endpoints comparing baseline to week 8:
9. COPD clinical questionnaire
10. Blood eosinophils and neutrophils
11. Blood C reactive protein (CRP)
12. Airways resistance using the interrupter technique (RInT)
13. Other blood and sputum markers: MIPIa, TGFb1, neutrophil elastase, reactive oxygen species
Overall trial start date
01/04/2009
Overall trial end date
01/04/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males or females, aged between 18 to 80 years, inclusive
2. The patient has received verbal and written study information, all questions have been answered satisfactorily and a consent form has been personally signed and dated by the patient and the investigator
3. A diagnosis of obstructive lung disease (with reference to the International Primary Care Respiratory Group [IPCRG] guidelines). This being evidenced as a post-bronchodilator ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) less than 0.7 at visit 1 or 2
4. The patient has a post-bronchodilator FEV1 of greater than 40% and less than 80% at visit 1 or 2
5. Patients have a history of regular sputum production (greater than 3 days per week)
6. Leicester Cough Questionnaire (LCQ) score of less than 17 (higher score indicates improvement)
7. A Medical Research Council (MRC) dyspnoea score of 3 or more
8. Females must be post-menopausal (greater than 1 year), surgically sterilised or using adequate hormonal contraception, intrauterine device), not breast feeding and have a negative serum pregnancy test
9. The patient must have a satisfactory health with the exception of obstructive lung disease as determined by the investigator on the basis of medical history and physical examination
10. In the Investigator's judgement, the patient is able and willing to comply with study visits and procedures (including laboratory tests, lung function tests)
11. Subjects must be able to demonstrate ability to use salbutamol metered-dose inhalor (MDI) during the screening period
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
164
Participant exclusion criteria
1. The patient has currently poorly controlled disease defined as requiring a course of oral or parenteral corticosteroids or an exacerbation of their obstructive lung disease in the three months prior to visit 2
2. The patient has had a recent change in maintenance therapy (i.e. within 6 weeks)
3. Maintenance oral corticosteroid treatment or use of unlicensed doses of inhaled corticosteroid medication (greater than 2000 µg beclomethasone diproprionate/day or equivalent)
4. The patient has seasonal disease alone
5. The patient has any known laboratory abnormality, which in the opinion of the investigator, would contraindicate study participation, including, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 1.5 x upper limit of normal (ULN) or creatinine greater than 1.5 mg/dL
6. The patient is unable to discontinue short-acting beta-2-adrenergic agonists for at least 4 hours, long-acting beta agonists (12 hours) and tiotropium (24 hours) prior to visit 2 (week 0)
7. The patient has chronic heart failure class III or IV (New York Heart Association) or a recent (less than six months) history of stroke, transient ischaemic attack or myocardial infarction
8. The patient is not able to follow study procedures (e.g., language problems, psychological disorders) or is considered to be non-compliant according to the investigator
9. The patient has a history of known alcohol or substance abuse (excluding cigarettes) within the one-year prior to visit 1
10. The patient has an active malignancy of any type or history of a malignancy (with the exception of patients with malignancy surgically removed with no evidence of recurrence within five years before enrolment, and patients with history of treated basal cell carcinoma)
11. The patient has any other severe or acute or chronic medical or psychiatric conditions that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Subjects with a malignancy and who are currently undergoing radiation therapy or have had chemotherapy within 5 years.
12. The patient has difficulty swallowing capsules or tablets, dysphagia or is unable to tolerate oral medication
13. The patient has been previously admitted to the study or currently participating or have recently participated in another trial with an investigational drug within 90 days of the start of this study
Recruitment start date
01/04/2009
Recruitment end date
01/04/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Biomedicine Group
Norwich
NR4 7TJ
United Kingdom
Funders
Funder type
Charity
Funder name
International Primary Care Research Group (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list