A Study to Evaluate the Anti-inflammatory Effects of Solithromycin in Chronic Obstructive Pulmonary Disease

NCT02628769 | Terminated Phase 2 Results DMC

• 3 other identifiers: CE01-2042014-003077-4214/LO/2066
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Solithromycin; Chronic Obstructive Pulmonary Disease; Inflammation; Macrolide

Outcome Measures

Primary Outcomes (1)

• Number of Sputum Neutrophils Per mL at 28 Days

  A number of sputum neutrophils per mL after treatment with solithromycin and placebo.

  28 days

Secondary Outcomes (11)

• Concentrations of Sputum CXCL8 at 28 Days

  28 days

• Concentrations of Sputum IL-6 Before and After Treatment With Solithromycin and Placebo at 28 Days

  28 days

• Concentrations of Sputum MPO Before and After Treatment With Solithromycin and Placebo at 28 Days

  28 days

• Concentrations of Sputum MMP-9 Before and After Treatment With Solithromycin and Placebo at 28 Days

  28 days

• Concentrations of Sputum MCP-1 Before and After Treatment With Solithromycin and Placebo.

  28 days

Other Outcomes (5)

• Exploratory Outcome: Activity of HDAC2 in Sputum Macrophages From Patients, Before and After Treatment With Solithromycin and Placebo.

  28 days

• Exploratory Outcome: Activity of PI3K in Sputum Macrophages From Patients, Before and After Treatment With Solithromycin and Placebo.

  84 days

• Exploratory Outcome: Activity of NF-κB in Sputum Macrophages From Patients, Before and After Treatment With Solithromycin and Placebo.

  28 days

Study Arms (2)

Solithromycin

EXPERIMENTAL

28 day treatment of 400 mg Solithromycin taken once a day.

Drug: Solithromycin

Placebo

PLACEBO COMPARATOR

28 day treatment with placebo taken once per day.

Drug: Placebo

Interventions

Solithromycin DRUG

Also known as: CEM-101

Solithromycin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of cigarette smoking \>10 pack-years.
• Post-bronchodilator FEV1/FVC of \<0.70 and FEV1 of 30-79% of predicted normal value.
• Patients on prescribed inhaled corticosteroids can be enrolled.
• Females of non-childbearing potential: surgically sterile (e.g. tubal ligation) or at least 2 years post-menopausal.
• 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.
• The patient must be willing and able to comply with all study visits and procedures.
• The patient must be a suitable candidate for oral therapy and be able to swallow capsules intact.
• The patient must provide written informed consent.
• No evidence of active bacterial infection in sputum by qPCR evaluation.

You may not qualify if:

• Acute exacerbation of COPD within the previous 60 days or during the washout period of the study.
• Any condition that could possibly affect oral drug absorption, e.g. gastroenteritis, status post gastrectomy, status post bariatric surgery.
• Currently taking medication for HIV, chronic hepatitis B, or hepatitis C virus (HCV) infection.
• Currently taking theophylline or other xanthine medication.
• Currently taking warfarin.
• Known concomitant infection (pulmonary or otherwise) which would require additional systemic antibiotics.
• QTc greater than 450 msec for males or females as corrected by the Fridericia formula.
• Current use of drugs known to prolong the QT interval, including Class Ia (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmics.
• 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.
• 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.
• 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).
• History of organ transplant.
• Cytotoxic chemotherapy or radiation therapy within the previous 3 months.
• Known neuromuscular disorder from clinical history (e.g. myasthenia gravis, Parkinson's disease).
• Known significant renal, hepatic, or hematologic impairment.

Sponsors & Collaborators

• Imperial College London: lead
• Melinta Therapeutics, Inc.: collaborator

Study Sites (1)

Muscle Lab, Respiratory Medicine, Harefield Hospital

Harefield, Middlesex, UB9 6JH, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Inflammation

Interventions

solithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Louise Donnelly
• Organization: Imperial College London

l.donnelly@imperial.ac.uk

+44 02075947895

Study Officials

• Peter J Barnes, FRS, FMedSci

  Imperial College London

  PRINCIPAL INVESTIGATOR

• William Man, MBBS, PhD

  Royal Brompton & Harefield NHS Foundation Trust

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 11, 2015
• Study Start: July 1, 2015
• Primary Completion: January 5, 2017
• Study Completion: January 5, 2017
• Last Updated: December 30, 2019
• Results First Posted: December 30, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)