Inflammatory Disorder of the Respiratory TractPhase 1NCT02307162
SAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects
A Phase 1 study testing RPL554 in people with Inflammatory Disorder of the Respiratory Tract and Chronic Obstructive Pulmonary Disorder, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 1 site in United Kingdom.
Trial summary
The purpose of the study is to assess the safety of single doses and multiple doses of a new formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary disorder. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Disorder of the Respiratory Tract, Chronic Obstructive Pulmonary Disorder
- What is being tested?
- RPL554
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2014to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed consent
- Males following contraception requirements, and agree not to donate sperm during study
- 12-lead ECG within normal range and no clinically significant abnormality
- Screening Holter report (minimum 18 hours) recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of subject safety or which may significantly impair interpretation
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
- Body weight ≥50 kg.
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- Negative for HIV, HBV and HCV
- Negative cotinine tests prior to randomisation.
- Additional Inclusion Criteria - Healthy Subjects (Parts A and B) only:
- Males aged 18 and 50 years
- Considered to be healthy
- Vital sign assessments within ranges:
- Systolic blood pressure 90 to 140 mmHg
- Diastolic blood pressure 50 to 90 mmHg
- Heart rate 45 to 90 bpm
- BMI 18 and 33 kg/m2 .
- Spirometry readings (FEV1 and FVC) ≥80% of predicted normal.
- Never smoked or is ex-smoker for ≥12 months with a smoking history of <5 pack years
- Additional Inclusion Criteria - COPD Subjects (Part C) only:
- Male and females aged 40 to 75 years
- If female must be of non-childbearing potential (postmenopausal or permanently sterilised)
- BMI 18 and 33 kg/m2 (inclusive).
- COPD diagnosis (defined by ATS/ERS guidelines Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year
- As defined in GOLD guidelines 2014: Post-bronchodilator spirometry at screening:
- Post-salbutamol FEV1/FVC ratio 0.70
- Post-salbutamol FEV1 ≥50 % and ≤80% of predicted normal
- No current conditions that may significantly impair subject compliance, safety or influence study results.
- Vital sign assessments within ranges:
- Systolic blood pressure 100 to 160 mmHg
- Diastolic blood pressure 50 to 90 mmHg
- Heart rate 45 to 90 bpm
- Clinically stable COPD in the last 4 weeks
- Chest X-ray (post anterior) at screening, or within 6 months prior to screening showing no abnormalities, which are both clinically significant and unrelated to COPD.
- Meet the concomitant medication restrictions
- An ex-smoker for ≥6 months with a smoking history of ≥10 pack years
- Capable of withdrawing from regular bronchodilators
Who cannot join
- Respiratory tract infection (both upper and lower) treated with antibiotics in last 12 weeks
- Clinically significant abnormal values for safety laboratory tests or physical examination
- History or suspected history of drug or alcohol abuse within the past 5 years.
- Known allergy to the study drug or any of the excipients of the formulation.
- Donated blood or blood products or had substantial loss of blood (more than 500 mL) in last 4 weeks or intention to donate blood or blood products during the study.
- Received an experimental drug or used an experimental medical device within 3 months or within a period less than 5 times the drug's half-life, whichever is longer
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- Pre-planned surgery or procedures that would interfere with the conduct of the study.
- Employee of the Investigator or study site or family members of the employees or the Investigator.
- History of regular alcohol consumption within last 6 months
- Unable or unwilling to comply fully with the study protocol.
- Mentally or legally incapacitated.
- Unable or unwilling to undergo multiple venepuncture procedures or having poor access to veins suitable for cannulation.
- History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
- Any other reason that the Investigator considers makes the subject unsuitable to participate.
- Additional Exclusion Criteria - Healthy Subjects (Parts A and B) only
- -Positive test for alcohol or drugs of abuse
- Additional Exclusion Criteria - COPD Subjects (Part C) only
- Positive test for alcohol or drugs of abuse prior to randomisation (unless explained by the subject's medication).
- A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral steroids within the last 12 months
- A history of one or more hospitalization for COPD in last 12 months
- Evidence of cor pulmonale or clinically significant pulmonary hypertension.
- Other respiratory disorders: Subjects with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha1-AT deficiency or other active pulmonary diseases.
- Previous lung resection or lung reduction surgery.
- Active participation in a pulmonary rehabilitation program.
- History of chronic uncontrolled disease that the Investigator believes are clinically significant.
- Documented severe cardiovascular disease: angina, recent or suspected myocardial infarction, History of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
- Major surgery, (requiring general anaesthesia) within last 6 weeks before the screening visit, or will not have fully recovered from surgery, or planned surgery through the end of the study.
- History of significant non compliance in previous investigational studies or with prescribed medications.
- Requires oxygen, even on an occasional basis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomised, Double Blind, Placebo Controlled, 3-part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Inhaled Doses of RPL554 Administered by Nebuliser to Healthy Male Subjects and Stable COPD Subjects.
The purpose of the study is to assess the safety of single doses and multiple doses of a new formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary disorder.
Read the detailed description
This is a randomised, double blind, placebo controlled study of a new suspension formulation of RPL554 comprising a Single Ascending Dose (SAD) phase (Part A) in healthy subjects, a Multiple Ascending Dose (MAD) phase (Part B) in healthy subjects and a MAD phase (Part C) in stable chronic obstructive pulmonary disease (COPD) subjects. Each cohort should comprise 10 subjects in a 7 active: 3 placebo ratio
Subjects will be screened in the 14 days before the first dose of study drug and have an end of study visit 4 to 10 days after the last dose of study drug.
Part A. Single Ascending Dose Study in Healthy Male Subjects aged 18-50. Each subject will receive a single dose of study drug. The starting dose will be 1.5 mg with planned escalation as 2 fold multiples unless the safety data indicates the escalation should be at smaller intervals. If RPL554 is not well tolerated at a particular dose level, the dose may be reduced for the next cohort.The decision on whether or not to escalate to each new dose level, and the dose, will be based on a formal review by the Dose Review Group (DRG).
Part B. Multiple Ascending Dose Study in Healthy Male Subjects aged 18-50. The starting dose for Part B will be determined from the data in Part A of the study. Each subject will receive the following doses of study drug and will be confined to the study centre during dosing: three doses at intervals of 8 hours on Days 1 to 5, followed by a single morning dose on Day 6.
The DRG may determine on the basis of safety or PK data that the dosing interval for subsequent cohorts will be every 12 hours, rather than every 8 hours.
Part C. Multiple Ascending Dose in moderate, stable COPD Subjects aged 40-75 Subjects will have no known significant concurrent diseases, will not have had a recent exacerbation, and will be expected to be able to withhold regular bronchodilator therapy for the duration of the treatment phase of the study. Rescue medication with ipratropium will be allowed (and its use recorded) and subjects may continue inhaled corticosteroids at a stable dose.
The dosing schedule will be the same as for Part B
Dose Escalation Procedures The decision on whether or not to escalate to each new dose level and from one part of the study to the next and the selected dose will be based on a formal review by the DRG of safety data.
The DRG will include the Principal Investigator and Sponsor's Medical Expert (and/or delegates) and will meet by teleconference to review safety data for each cohort. The DRG will review all available safety data (including adverse events [AEs], safety laboratory tests, spirometry and ECG data) collected up to 24 hours post dose for Part A, and for up to 24 hours post final dose for Parts B and C.
Data collected during the study will be entered on case report forms and transferred to a database using double entry. Blinding will be maintained until all queries are resolved and the database is locked. AEs will be summarised by study treatment and further by intensity and relationship to study treatment. The study will primarily be evaluated using descriptive statistics.
The sample size selected is not based on any formal power calculation.
- Being tested
- RPL554, Placebo
- Keywords
- COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPL554Drug
Phosphodiesterase 3 and 4 Inhibitor
PlaceboDrug
Dummy solution
| Study group | Role | What they receive |
|---|---|---|
| Dummy solution | Placebo comparator | Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C) Receives: Drug: Placebo |
| RPL554 suspension | Experimental | Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C).
Starting dose in Part A to be 1.5mg/mL with planned up to 2 fold increments. Doses in Part B will be selected from Part A. Doses in Part C to be selected from Part B Receives: Drug: RPL554 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Adverse events
Measured: From screening until last visit (up to 10 days after last dose)
Vital signs
Blood pressure and pulse rate
Measured: Pre-dose, up to 24 hours post last dose and last visit
Laboratory safety assessments
Biochemistry, haematology and urinalysis
Measured: Pre-dose, up to 24 hours post last dose and last visit
ECG
ECG
Measured: Pre-dose, up to 24 hours post last dose and last visit
Physical Examination
Measured: Pre-dose, 24 hours post last dose and last visit
Holter Monitoring
Continuous heart monitoring
Measured: 24 hours post dose
Secondary outcomes (1)
Pharmacokinetics (trough measurement Blood sampling for RPL554 concentration)
Blood sampling for RPL554 concentration
Measured: 24 hour profile after first and last dose, trough measurement on Days 2-5 for Parts B and C
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Disorder of the Respiratory TractStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dave Singh, Principal investigator, Medicines Evaluation Unit, Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02307162
- Sponsor's protocol ID
- RPL554-007-2014
- Status last verified
- Oct 2015
- First submitted
- 30 Nov 2014
- Last updated
- 28 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomised, Double Blind, Placebo Controlled, 3-part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Inhaled Doses of RPL554 Administered by Nebuliser to Healthy Male Subjects and Stable COPD Subjects.
- ClinicalTrials.gov ID
- NCT02307162
- Acronym / sponsor ID
- RPL554-007-2014
- Keywords
- COPD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the safety of single doses and multiple doses of a new formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary disorder.
Detailed description
This is a randomised, double blind, placebo controlled study of a new suspension formulation of RPL554 comprising a Single Ascending Dose (SAD) phase (Part A) in healthy subjects, a Multiple Ascending Dose (MAD) phase (Part B) in healthy subjects and a MAD phase (Part C) in stable chronic obstructive pulmonary disease (COPD) subjects. Each cohort should comprise 10 subjects in a 7 active: 3 placebo ratio
Subjects will be screened in the 14 days before the first dose of study drug and have an end of study visit 4 to 10 days after the last dose of study drug.
Part A. Single Ascending Dose Study in Healthy Male Subjects aged 18-50. Each subject will receive a single dose of study drug. The starting dose will be 1.5 mg with planned escalation as 2 fold multiples unless the safety data indicates the escalation should be at smaller intervals. If RPL554 is not well tolerated at a particular dose level, the dose may be reduced for the next cohort.The decision on whether or not to escalate to each new dose level, and the dose, will be based on a formal review by the Dose Review Group (DRG).
Part B. Multiple Ascending Dose Study in Healthy Male Subjects aged 18-50. The starting dose for Part B will be determined from the data in Part A of the study. Each subject will receive the following doses of study drug and will be confined to the study centre during dosing: three doses at intervals of 8 hours on Days 1 to 5, followed by a single morning dose on Day 6.
The DRG may determine on the basis of safety or PK data that the dosing interval for subsequent cohorts will be every 12 hours, rather than every 8 hours.
Part C. Multiple Ascending Dose in moderate, stable COPD Subjects aged 40-75 Subjects will have no known significant concurrent diseases, will not have had a recent exacerbation, and will be expected to be able to withhold regular bronchodilator therapy for the duration of the treatment phase of the study. Rescue medication with ipratropium will be allowed (and its use recorded) and subjects may continue inhaled corticosteroids at a stable dose.
The dosing schedule will be the same as for Part B
Dose Escalation Procedures The decision on whether or not to escalate to each new dose level and from one part of the study to the next and the selected dose will be based on a formal review by the DRG of safety data.
The DRG will include the Principal Investigator and Sponsor's Medical Expert (and/or delegates) and will meet by teleconference to review safety data for each cohort. The DRG will review all available safety data (including adverse events [AEs], safety laboratory tests, spirometry and ECG data) collected up to 24 hours post dose for Part A, and for up to 24 hours post final dose for Parts B and C.
Data collected during the study will be entered on case report forms and transferred to a database using double entry. Blinding will be maintained until all queries are resolved and the database is locked. AEs will be summarised by study treatment and further by intensity and relationship to study treatment. The study will primarily be evaluated using descriptive statistics.
The sample size selected is not based on any formal power calculation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dummy solution | Placebo comparator | Drug: PlaceboNebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C) |
| RPL554 suspension | Experimental | Drug: RPL554Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C). Starting dose in Part A to be 1.5mg/mL with planned up to 2 fold increments. Doses in Part B will be selected from Part A. Doses in Part C to be selected from Part B |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Informed consent
- Males following contraception requirements, and agree not to donate sperm during study
- 12-lead ECG within normal range and no clinically significant abnormality
- Screening Holter report (minimum 18 hours) recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of subject safety or which may significantly impair interpretation
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
Key exclusion criteria (30 listed)
- Respiratory tract infection (both upper and lower) treated with antibiotics in last 12 weeks
- Clinically significant abnormal values for safety laboratory tests or physical examination
- History or suspected history of drug or alcohol abuse within the past 5 years.
- Known allergy to the study drug or any of the excipients of the formulation.
- Donated blood or blood products or had substantial loss of blood (more than 500 mL) in last 4 weeks or intention to donate blood or blood products during the study.
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 |
|---|---|---|
| RPL554Phosphodiesterase 3 and 4 Inhibitor | Drug | RPL554 suspension |
| PlaceboDummy solution | Drug | Dummy solution |
Primary outcome
Adverse events
Time frame: From screening until last visit (up to 10 days after last dose)
Adverse events
Vital signs
Time frame: Pre-dose, up to 24 hours post last dose and last visit
Blood pressure and pulse rate
Laboratory safety assessments
Time frame: Pre-dose, up to 24 hours post last dose and last visit
Biochemistry, haematology and urinalysis
ECG
Time frame: Pre-dose, up to 24 hours post last dose and last visit
ECG
Physical Examination
Time frame: Pre-dose, 24 hours post last dose and last visit
Holter Monitoring
Time frame: 24 hours post dose
Continuous heart monitoring
1 secondary outcome
Pharmacokinetics (trough measurement Blood sampling for RPL554 concentration)
Time frame: 24 hour profile after first and last dose, trough measurement on Days 2-5 for Parts B and C
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
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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.
Dave Singh principal investigator
Medicines Evaluation Unit, Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RPL554 in people with Inflammatory Disorder of the Respiratory Tract and Chronic Obstructive Pulmonary Disorder, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA 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 36 inclusion and 30 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: finished, as of the sponsor's last update on 28 Oct 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (time frame: From screening until last visit (up to 10 days after last dose)). The study lists 6 primary outcomes in all. 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 28 Oct 2015.