Pulmonary Disease, Chronic ObstructivePhase 2NCT02628769
A Study to Evaluate the Anti-inflammatory Effects of Solithromycin in Chronic Obstructive Pulmonary Disease
A Phase 2 study testing Solithromycin in people with Pulmonary Disease, Chronic Obstructive, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Solithromycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2015to 5 Jan 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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.
- Women who are pregnant or breast feeding
- Prior participation in this protocol.
- Any investigational drugs taken or investigational devices used within 4 weeks before administration of the first dose of the study drug.
- History of intolerance or hypersensitivity to macrolide antibiotics.
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Muscle Lab, Respiratory Medicine, Harefield Hospital
Harefield, Middlesex, UB9 6JH
About this study
Official title: A Single-center, Double-blind, Randomised, Placebo-controlled Crossover Study to Evaluate the Effect of Solithromycin on Airway Inflammation in Male and Female Patients With Chronic Obstructive Pulmonary Disease
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.
Read the detailed description
Chronic obstructive pulmonary disease (COPD) is a common and debilitating respiratory illness, that kills around 30,000 people annually in the UK. The primary risk factor is cigarette smoking, which causes inflammation in the air passages of the lungs. This inflammation is irreversible and results in progressive lung destruction. Currently, there are no effective anti-inflammatory medications available for COPD.
Inhalers remain the mainstay of regular treatment for COPD. Macrolide antibiotics however, are occasionally used as a supplementary treatment for some patients. They have been shown to be anti-inflammatory. However, concerns exist over the development of bacterial resistance to such antibiotics. Consequently they are not widely prescribed for COPD. Solithromycin is a new macrolide antibiotic, which has been shown to possess superior anti-inflammatory properties. Importantly, bacteria are far less likely to develop resistance to this new medication.
The current study will assess the effect of solithromycin as an anti-inflammatory treatment for COPD. 30 patients will be recruited to receive 28 days of treatment with solithromycin or placebo, followed by a 28 day wash out period (no study medication), before taking a further 28 days of treatment (the medication not taken first time around, i.e. either solithromycin or placebo). This study is a single-centre (Harefield Hospital), double-blind (study team and patient are not told what treatment they are taking), randomised (order in which solithromycin and placebo are taken), placebo-controlled and has a crossover design (subjects take both solithromycin and placebo separately). Sputum, blood and fluid from the nasal lining will be periodically sampled to examine any effect on the levels of inflammatory cells and proteins during the study. Any changes in lung function parameters or symptoms (COPD Assessment Test) will also be assessed.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Solithromycin, Placebo
- Keywords
- Solithromycin, Chronic Obstructive Pulmonary Disease, Inflammation, Macrolide
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SolithromycinDrug
Also called CEM-101
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Solithromycin | Experimental | 28 day treatment of 400 mg Solithromycin taken once a day. Receives: Drug: Solithromycin |
| Placebo | Placebo comparator | 28 day treatment with placebo taken once per day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Sputum Neutrophils Per mL at 28 Days
A number of sputum neutrophils per mL after treatment with solithromycin and placebo.
Measured: 28 days
Secondary outcomes (11)
Concentrations of Sputum CXCL8 at 28 Days
Concentrations of sputum CXCL8 after treatment with solithromycin and placebo.
Measured: 28 days
Concentrations of Sputum IL-6 Before and After Treatment With Solithromycin and Placebo at 28 Days
Measured: 28 days
Concentrations of Sputum MPO Before and After Treatment With Solithromycin and Placebo at 28 Days
Measured: 28 days
Concentrations of Sputum MMP-9 Before and After Treatment With Solithromycin and Placebo at 28 Days
Measured: 28 days
Concentrations of Sputum MCP-1 Before and After Treatment With Solithromycin and Placebo.
Measured: 28 days
Concentrations of Sputum TNF-α Before and After Treatment With Solithromycin and Placebo.
Measured: 28 days
Concentrations of CXCL8 in Nasal Lining Fluid With Solithromycin and Placebo at 28 Days
Measured: 28 days
FEV1 After Treatment With Solithromycin and Placebo at 28 Days
Measured: 28 days
R5-R20 After Treatment at 28 Days
R5-R20 assessed by impulse oscillometry after treatment with solithromycin and placebo.
Measured: 28 days
COPD Assessment Test (CAT) Scores
COPD Assessment Test (CAT) scores after treatment with solithromycin and placebo.
score of 0-40 to indicate the impact of the disease, the higher score better outcome
Measured: 28 days
The Number of Adult COPD Patients With Treatment-related Adverse Events, as Assessed by CTCAE v4.0.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startJul 2015
- Primary completion5 Jan 2017
- Study completion5 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Melinta Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Peter J Barnes, FRS, FMedSci, Principal investigator, Imperial College LondonWilliam Man, MBBS, PhD, Study chair, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02628769
- Sponsor's protocol ID
- CE01-204
- Other IDs
- 2014-003077-42, 14/LO/2066, 2014
- Status last verified
- Dec 2019
- First submitted
- 1 Dec 2015
- Last updated
- 30 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Double-blind, Randomised, Placebo-controlled Crossover Study to Evaluate the Effect of Solithromycin on Airway Inflammation in Male and Female Patients With Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT02628769
- Acronym / sponsor ID
- CE01-204
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Solithromycin, Chronic Obstructive Pulmonary Disease, Inflammation, Macrolide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Melinta Therapeutics, Inc.
- Study start
- Jul 2015 (actual)
- Primary completion
- 5 Jan 2017 (actual)
- Study completion
- 5 Jan 2017 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Posted 30 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Chronic obstructive pulmonary disease (COPD) is a common and debilitating respiratory illness, that kills around 30,000 people annually in the UK. The primary risk factor is cigarette smoking, which causes inflammation in the air passages of the lungs. This inflammation is irreversible and results in progressive lung destruction. Currently, there are no effective anti-inflammatory medications available for COPD.
Inhalers remain the mainstay of regular treatment for COPD. Macrolide antibiotics however, are occasionally used as a supplementary treatment for some patients. They have been shown to be anti-inflammatory. However, concerns exist over the development of bacterial resistance to such antibiotics. Consequently they are not widely prescribed for COPD. Solithromycin is a new macrolide antibiotic, which has been shown to possess superior anti-inflammatory properties. Importantly, bacteria are far less likely to develop resistance to this new medication.
The current study will assess the effect of solithromycin as an anti-inflammatory treatment for COPD. 30 patients will be recruited to receive 28 days of treatment with solithromycin or placebo, followed by a 28 day wash out period (no study medication), before taking a further 28 days of treatment (the medication not taken first time around, i.e. either solithromycin or placebo). This study is a single-centre (Harefield Hospital), double-blind (study team and patient are not told what treatment they are taking), randomised (order in which solithromycin and placebo are taken), placebo-controlled and has a crossover design (subjects take both solithromycin and placebo separately). Sputum, blood and fluid from the nasal lining will be periodically sampled to examine any effect on the levels of inflammatory cells and proteins during the study. Any changes in lung function parameters or symptoms (COPD Assessment Test) will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Solithromycin | Experimental | Drug: Solithromycin28 day treatment of 400 mg Solithromycin taken once a day. |
| Placebo | Placebo comparator | Drug: Placebo28 day treatment with placebo taken once per day. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SolithromycinAlso: CEM-101 | Drug | Solithromycin |
| Placebo | Drug | Placebo |
Primary outcome
Number of Sputum Neutrophils Per mL at 28 Days
Time frame: 28 days
A number of sputum neutrophils per mL after treatment with solithromycin and placebo.
11 secondary outcomes
Concentrations of Sputum CXCL8 at 28 Days
Time frame: 28 days
Concentrations of Sputum IL-6 Before and After Treatment With Solithromycin and Placebo at 28 Days
Time frame: 28 days
Concentrations of Sputum MPO Before and After Treatment With Solithromycin and Placebo at 28 Days
Time frame: 28 days
Concentrations of Sputum MMP-9 Before and After Treatment With Solithromycin and Placebo at 28 Days
Time frame: 28 days
Concentrations of Sputum MCP-1 Before and After Treatment With Solithromycin and Placebo.
Time frame: 28 days
Concentrations of Sputum TNF-α Before and After Treatment With Solithromycin and Placebo.
Time frame: 28 days
Concentrations of CXCL8 in Nasal Lining Fluid With Solithromycin and Placebo at 28 Days
Time frame: 28 days
FEV1 After Treatment With Solithromycin and Placebo at 28 Days
Time frame: 28 days
R5-R20 After Treatment at 28 Days
Time frame: 28 days
COPD Assessment Test (CAT) Scores
Time frame: 28 days
The Number of Adult COPD Patients With Treatment-related Adverse Events, as Assessed by CTCAE v4.0.
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Pulmonary Disease, Chronic Obstructive
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Barnes, FRS, FMedSci principal investigator
Imperial College London
William Man, MBBS, PhD study chair
Royal Brompton & Harefield NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Solithromycin in people with Pulmonary Disease, Chronic Obstructive, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Sputum Neutrophils Per mL at 28 Days (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2019.