IMD-1041 Chronic Obstructive Pulmonary Disease: Proof of Concept (POC) Study — COPD  

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title: A Phase IIa, Proof of Concept Study to Evaluate the Reduction in Inflammatory Biomarkers and Assess Airway Function Following Administration of IMD-1041 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Status Active, not recruiting

Clinical Trial Summary

COPD is a lung disease in which the lung is damaged, making it hard to breathe. In COPD, the airways/tubes that carry air in and out of the lungs are partly obstructed, making it difficult to get air in and out. COPD gets gradually worse over time. At the moment there is no cure for COPD. The best way to slow the disease is to stop smoking. Current medications are used to alleviate shortness of breath and cough, and to treat infections of the lungs that can worsen COPD.

Institute of Medicinal Molecular Design, Inc. (IMMD), a Japanese Drug Discovery Company is developing a compound code named IMD-1041. IMD-1041 is an investigational drug, meaning it is not yet on the market. It is an IKKb inhibitor developed for the treatment of COPD. Unlike most other medications used for COPD currently, IMD-1041 is in capsule form and needs to be taken twice a day. It is also unlike all other drugs in use because it treats the underlying cause of the symptoms.

The purpose of this study is to see if IMD-1041 has the ability to reduce inflammatory derived symptoms and airway remodelling (changes) by looking at certain changes in chemical levels in the blood and sputum (phlegm).

Clinical Trial Description

The dose level of IMD 1041 has been selected based on previous clinical trials. The dose to be studied, 400mg, is considered to be efficacious, and is supported by the clinical data in healthy subjects and type 2 diabetic patients.

Single oral doses of 800 mg and multiple oral doses of 400 mg twice daily of IMD-1041 have been shown to be safe and well tolerated by healthy subjects.

Twice daily doses of 200 mg of IMD-1041 have been shown to be safe and well tolerated when given to diabetic patients for 12 weeks.

A placebo (dummy medication) arm has been selected as it is considered the most reliable method to minimise patient and investigator bias and current COPD guidelines suggest the most useful comparison would be with placebo. Exposure placebo will allow a reliable evaluation of IMD 1041, as well as the adverse events caused by the drug compared to those resulting from the COPD natural course.

All patients will be able to remain on the current medications apart from theophylline which is expected to have effects on IKK beta.

The current treatments for COPD do not include a medication of this mechanism of action, who's main aim is to reduce inflammatory and fibrotic changes which cause the symptoms which current standard COPD medications treat.

The study will last for 12-14 weeks, including a 7 day screening period, visit 0 baseline/randomisation visit, visit 1 and visit 3 for all study spec tests, visit 2 and 4/follow up as either a site or telephone contact to check subject compliance and adverse events.

Prior to selection the Investigator will evaluate the eligibility of patients for entry into the trial by reviewing the patients' medical records against the inclusion/exclusion criteria specified in the protocol.

There will be a potential pre-screening visit up to 3 weeks prior to randomisation. This visit will only be applicable for patients who need to stop the medication theophylline which need to be stopped 2 weeks prior to screening. At this visit potential patients will be provided with the information about study activities and requirements. After signing the informed consent form the patient will be asked to stop the medication and return to the study site for screening at least 2 weeks after the visit.

All patients will attend the clinical site for initial screening up to 7 days prior to randomisation. If the patient has not been 'pre-screened' as described above, they will be given information pertaining to study activities and requirements. After signing the informed consent form evaluations will be performed to confirm the patients' eligibility according to the study protocol. The patients' medical history, physical examination, clinical laboratory tests, electrocardiogram (ECG) tracing, blood pressure, pregnancy screening (women of child bearing potential only) will be performed. Blood will be taken for routine clinical laboratory testing.

Following successful screening, patients will return to the site up to seven days (but at least 1 day) after the screening visit for randomisation. There will be a 50:50 chance of the patient being randomised to either IMD 1041 or placebo of whichever they will remain on for the duration of the study. The following will then happen prior to randomisation:

• Patient asked about current health problems, adverse events and any changes to concomitant medications since screening.

• Vitals signs

• Blood will be taken for clinical lab evaluations and biomarker sampling

• Lung functions

• Induced sputum for biomarker sampling

• 2 questionnaires completed Following all of the above evaluations the patient will be randomised and medication dispensed. (A total of 280 tablets will be dispensed, which equates to 4 weeks supply, plus 56 tablets as spares in case of loss or delayed next visit.)

Visit 1 will occur 4 weeks after visit 0 (+/- 2 days). At this visit the following will occur:

• Patient asked about current health problems, adverse events and any changes to concomitant medications since screening.

• vitals signs

• Blood will be taken for clinical lab evaluations, PK analysis and biomarker sampling

• Lung functions

• Induced sputum for biomarker sampling

• Medication will be dispensed. A total of either 4(224) or 8(448) weeks supply will be dispensed depending on whether or not you will attend the clinical site for visit 3.

Visit 2 will occur 4 weeks after visit 1 (+/- 3 days). This visit will be either on site or over the telephone and will be decided by the Principal Investigator on a case-by-case basis. At this visit the following will occur:

• Patient asked about current health problems, adverse events and any changes to concomitant medications since screening.

• Medication dispensed. A total of 4 weeks supply (224 tablets) will be dispensed for patients who attend the site for this visit.

Visit 3 will occur up to 4 weeks after visit 2 (+/- 3 days). At this visit the following will occur:

• Patient asked about current health problems, adverse events and any changes to concomitant medications since screening.

• vitals signs

• Blood will be taken for clinical lab evaluations, PK analysis and biomarker sampling

• Lung functions

• Induced sputum for biomarker sampling

• 2 questionnaires completed

• All medication return and final accountability documented

Visit 4, the follow up visit will be via telephone and will occur 2 weeks after visit 3 (+/- 3 days). The following will occur:

• Patient asked about current health problems, adverse events and any changes to concomitant medications since screening. ;

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT00883584
• Study type: Interventional
• Source: Institute of Medicinal Molecular Design, Inc.
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 2008
• Completion date: May 2009