A clinical trial assessing the effect of a new antibiotic (Solithromycin) on inflammation in the small air passages of patients with chronic obstructive pulmonary disease.

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2014-003077-42-GB
• Lead Sponsor: Imperial College, London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-24
• Study Completion: 2017-01-05
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 6

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 <0.70 and FEV1 of 30-79% of the predicted normal value.
4. Patients on prescribed inhaled corticosteroids can be enrolled.
5. Females of non-childbearing potential who are either surgically sterile (e.g. tubal ligation) or at least 2 years post-menopausal.
6. Females of childbearing potential (including females less than 2 years post-menopausal) who have a negative pregnancy test at enrollment and agree to use highly effective methods of birth control (i.e. diaphragm plus spermicide or male condom plus spermicide, oral contraceptive in combination with a second method, contraceptive implant, injectable contraceptive, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in the study and for 30 days after the last dose of study drug.
7. The patient must be a suitable candidate for oral therapy and be able to swallow capsules intact.
8. No evidence of active bacterial infection in sputum by qPCR evaluation.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

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).

Study & Design

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