A Study to Evaluate the Anti-inflammatory Effects of Solithromycin in Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Solithromycin; Placebo
Intervention MeSH terms: Solithromycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Solithromycin; Chronic Obstructive Pulmonary Disease; Inflammation; Macrolide

Summary:

      This study examines the potential benefit of a new antibiotic, Solithromycin, for the
      long-term treatment of Chronic Obstructive Pulmonary Disease (COPD). Solithromycin is
      hypothesised to work by reducing inflammation in the lungs of patients with COPD. Stable COPD
      patients will receive treatment with solithromycin for 28 days and comparisons will be made
      between any effects observed with Solithromycin and a placebo. This will include any changes
      in inflammatory proteins, lung function and reported symptoms.
    

Eligibility criteria:

        Inclusion Criteria:

          1. History of cigarette smoking >10 pack-years.

          2. Post-bronchodilator FEV1/FVC of <0.70 and FEV1 of 30-79% of predicted normal value.

          3. Patients on prescribed inhaled corticosteroids can be enrolled.

          4. Females of non-childbearing potential: surgically sterile (e.g. tubal ligation) or at
             least 2 years post-menopausal.

          5. Females of childbearing potential (including females less than 2 years
             post-menopausal) must have a negative pregnancy test at enrollment and must 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.

          6. The patient must be willing and able to comply with all study visits and procedures.

          7. The patient must be a suitable candidate for oral therapy and be able to swallow
             capsules intact.

          8. The patient must provide written informed consent.

          9. No evidence of active bacterial infection in sputum by qPCR evaluation.

        Exclusion Criteria:

          1. Acute exacerbation of COPD within the previous 60 days or during the washout period of
             the study.

          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 (pulmonary or otherwise) which would require additional
             systemic antibiotics.

          7. QTc greater than 450 msec for males or females 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).