Chronic Obstructive Pulmonary Disease. MedDRA version: 18.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Solithromycin
Product Code: CEM-101
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Solithromycin
CAS Number: 7609
Sponsors
Imperial College, London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients greater than 45 years of age. 2. History of cigarette smoking more than 10 pack-years. 3. FEV1/FVC of =65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Acute exacerbation of COPD within the previous 60 days. 2. Any condition that could possibly affect oral drug absorption, e.g. gastroenteritis, status post gastrectomy, status post bariatric surgery. 3. Currently taking medication for HIV, chronic hepatitis B, or hepatitis C virus (HCV) infection. 4. Currently taking theophylline or other xanthine medication. 5. Currently taking warfarin. 6. Known concomitant infection which would require additional systemic antibiotics. 7. QTc greater than 470 msec as corrected by the Fridericia formula. 8. Current use of drugs known to prolong the QT interval, including Class Ia (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmics. 9. Concomitant use of drugs, foods, or herbal products known to be moderate to potent inhibitors of CYP3A4 isozymes: oral antifungal agents (e.g. ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole); HIV protease inhibitors (e.g. ritonavir and saquinavir), HCV protease inhibitors (e.g. boceprevir and telaprevir), nefazodone, fluvoxamine, conivaptan, diltiazem, verapamil, aprepitant, ticlopidine, crizotinib, imatinib; grapefruit or grapefruit juice. 10. Any use within the prior 7 days of drugs or herbal products known to be moderate to potent inducers of CYP3A4 isozymes: St. John’s Wort, rifampin, rifabutin, anti-convulsants (e.g. phenobarbital, carbamazepine, phenytoin, rufinamide), modafinil, armodafinil, etraverine, efavirenz, bosentan. 11. Required current use of drugs with narrow therapeutic indices that are principally metabolized by CYP3A4 or transported by P-glycoprotein (P-gp), for which a drug interaction with solithromycin could result in higher and possibly unsafe exposures to these drugs: e.g. the P-gp substrates digoxin or colchicine and the CYP3A4 substrates alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, midazolam, pimozide, quinidine, sirolimus, tacrolimus, everolimus, and terfenadine). 12. History of organ transplant. 13. Cytotoxic chemotherapy or radiation therapy within the previous 3 months. 14. Known neuromuscular disorder from clinical history (e.g. myasthenia gravis, Parkinson’s disease). 15. Known significant renal, hepatic, or hematologic impairment. 16. Women who are pregnant or breast feeding 17. Prior participation in this protocol. 18. Any investigational drugs taken or investigational devices used within 4 weeks before administration of the first dose of the study drug. 19. History of intolerance or hypersensitivity to macrolide antibiotics. 20. Any concomitant condition that, in the opinion of the Investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy and follow-up could be completed (e.g. life expectancy <30 days).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: COPD results from chronic inflammation in the small passages of the lung. At present, there are no effective therapies capable of dampening this inflammation to prevent disease progression. Even steroids, which are normally potent anti-inflammatories, have little or no effect in COPD. Macrolide antibiotics have previously been shown to possess anti-inflammatory actions on cells of the immune system. In addition, they kill many different kinds of bacteria, which reside in the lungs of COPD patients and are responsible for perpetuating this inflammatory process. Although macrolides are occasionally used as an additional long-term therapy in some COPD patients, many clinicians are concerned that widespread use may lead to the generation of antibiotic resistance amongst many different kinds of bacteria. This could be catastrophic for COPD patients given the high frequency of chest infections and pneumonia. As such, the risks of long-term macrolide use are considered to outweigh any possbil; Secondary Objective: In healthy lungs, special white blood cells tightly regulate and coordinate inflammation through the release of important chemical signals. In COPD however, these same white blood cells are faulty and continually promote chemical release leading to inflammation and lung damage. This is the result of defective messages within the cell. Steroids are anti-inflammatory drugs normally capable of switching off these messages to halt the release of these pro-inflammatory chemicals. In other inflammatory lung conditions (e.g. asthma) they are highly effective medications. In COPD however, the cell messages are resistant to steroids and are not switched off. As such, steroids are ineffective anti-inflammatories for COPD. Solithromycin has previously been shown to suppress the faulty messages and subsequent release of inflammatory signals from cells grown in the laboratory. During these experiments it was also shown that sol | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Data will be collected to evaluate this endpoint throughout the two treatment periods, each of 28 days.; Secondary end point(s): To assess concentrations of sputum CXCL8, IL-6, MPO, MMP-9, and TNF-a, nasal CXCL8 and systemic biomarkers of inflammation (C-reative protein and fibrinogen) in patients treated with solithromycin compared to patients treated with placebo To assess forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), resistance at 5Hz (R5) and the COPD Assessment Test (CAT) score in patients treated with solithromycin compared to patients treated with placebo To assess the safety and tolerability of oral solithromycin in adult patients with COPD An exploratory end point will be to assess the activity of HDAC2, PI3K, NF-?B (and potentially other cytokines/chemokines) in sputum macrophages from patients treated with solithromycin compared to those patients treated with placebo. | — |
Countries
United Kingdom
Contacts
Public ContactLouise Donnelly
Imperial College London
Outcome results
None listed