Trial Outcomes & Findings for The Effects of RPL554 in Addition to Tiotropium in COPD Patients (NCT NCT03028142)
NCT ID: NCT03028142
Last Updated: 2019-02-27
Results Overview
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Day 3
Results posted on
2019-02-27
Participant Flow
74 were screened.Main reasons for screen failure were reversibility criteria not met (21), withdrew consent (5) and unsuitable chronic obstructive pulmonary disorder (COPD) history (4). Patients had to discontinue long acting bronchodilators on the day before screening and short acting bronchodilators for 8 hours before all spirometry assessments
Participant milestones
| Measure |
Placebo Then Low Dose RPL554 Then High Dose RPL554
Placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Low Dose Dose RPL554 Then High Dose RPL554 Then Placebo
1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
High Dose RPL554 Then Placebo Then Low Dose RPL554
High dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
High Dose RPL554 Then Low Dose RPL554 Then Placebo
High dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Low Dose RPL554 Then Placebo Then High Dose RPL554
Low dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Placebo Then High Dose RPL554 Then Low Dose RPL554
Placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
6
|
4
|
6
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
6
|
4
|
5
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebo Then Low Dose RPL554 Then High Dose RPL554
Placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Low Dose Dose RPL554 Then High Dose RPL554 Then Placebo
1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
High Dose RPL554 Then Placebo Then Low Dose RPL554
High dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
High Dose RPL554 Then Low Dose RPL554 Then Placebo
High dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Low Dose RPL554 Then Placebo Then High Dose RPL554
Low dose RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
Placebo Then High Dose RPL554 Then Low Dose RPL554
Placebo twice daily plus 10 mcg tiotropium once daily for 3 days then 6 mg RPL554 twice daily plus 10 mcg tiotropium once daily for 3 days then 1.5 mg RPL554 twice daily plus 10 mcg tiotropium for 3 days, with a 7-21 day washout period between treatments
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
The Effects of RPL554 in Addition to Tiotropium in COPD Patients
Baseline characteristics by cohort
| Measure |
Overall
n=30 Participants
All patients before the start of the study treatment sequence
|
|---|---|
|
Age, Continuous
|
64.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Percentage of predicted FEV1 post-bronchodilator
|
60.1 %
STANDARD_DEVIATION 9.73 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 3Population: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamics parameters on at least two treatment periods.
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
Outcome measures
| Measure |
Lower Dose Nebulised Treatment
n=28 Participants
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium dry powder inhaler (DPI) once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 Participants
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=27 Participants
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing
|
0.477 Liters
Standard Deviation 0.1673
|
0.500 Liters
Standard Deviation 0.2157
|
0.373 Liters
Standard Deviation 0.1970
|
PRIMARY outcome
Timeframe: Day 3Population: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamics parameters on at least two treatment periods.
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing
Outcome measures
| Measure |
Lower Dose Nebulised Treatment
n=28 Participants
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium dry powder inhaler (DPI) once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 Participants
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=27 Participants
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Average FEV1 Over 12 Hours on the Third Day of Dosing
|
3.804 Liters*hour
Standard Deviation 1.8512
|
3.967 Liters*hour
Standard Deviation 2.2134
|
3.197 Liters*hour
Standard Deviation 2.2826
|
SECONDARY outcome
Timeframe: Day 1Population: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamics parameters on at least two treatment periods.
Peak FEV1 over 4 hours on Day 1
Outcome measures
| Measure |
Lower Dose Nebulised Treatment
n=28 Participants
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium dry powder inhaler (DPI) once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 Participants
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=27 Participants
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Peak FEV1 on Day 1
|
0.383 Liters
Standard Deviation 0.1448
|
0.432 Liters
Standard Deviation 0.1720
|
0.337 Liters
Standard Deviation 0.1854
|
SECONDARY outcome
Timeframe: Day 1Average FEV1 AUC over 12 hours on Day 1
Outcome measures
| Measure |
Lower Dose Nebulised Treatment
n=28 Participants
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium dry powder inhaler (DPI) once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 Participants
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=27 Participants
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Average FEV1 Over 12 Hours on Day 1
|
3.058 Liters*hour
Standard Deviation 1.4851
|
3.094 Liters*hour
Standard Deviation 1.9624
|
2.510 Liters*hour
Standard Deviation 1.9381
|
Adverse Events
Lower Dose Nebulised Treatment
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Higher Dose Nebulised Treatment
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lower Dose Nebulised Treatment
n=29 participants at risk
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 participants at risk
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=28 participants at risk
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Infections and infestations
Pneumonia
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
Other adverse events
| Measure |
Lower Dose Nebulised Treatment
n=29 participants at risk
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
1.5 mg RPL554 plus tiotropium
|
Higher Dose Nebulised Treatment
n=27 participants at risk
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
6 mg RPL554 plus tiotropium
|
Placebo
n=28 participants at risk
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
Placebo plus tiotropium
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
7.1%
2/28 • Number of events 3 • From informed consent until the end of the study.
|
|
Nervous system disorders
Headache
|
6.9%
2/29 • Number of events 2 • From informed consent until the end of the study.
|
18.5%
5/27 • Number of events 8 • From informed consent until the end of the study.
|
10.7%
3/28 • Number of events 3 • From informed consent until the end of the study.
|
|
General disorders
Medical device site reaction
|
13.8%
4/29 • Number of events 4 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
14.3%
4/28 • Number of events 4 • From informed consent until the end of the study.
|
|
General disorders
Chest discomfort
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
7.1%
2/28 • Number of events 3 • From informed consent until the end of the study.
|
|
General disorders
Catheter site bruise
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
General disorders
Chills
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
General disorders
Fatigue
|
0.00%
0/29 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
3.6%
1/28 • Number of events 1 • From informed consent until the end of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Larngeal discomfort
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/29 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
3.6%
1/28 • Number of events 1 • From informed consent until the end of the study.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/29 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
3.6%
1/28 • Number of events 1 • From informed consent until the end of the study.
|
|
Infections and infestations
Pneumonia
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/29 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
3.6%
1/28 • Number of events 1 • From informed consent until the end of the study.
|
|
Infections and infestations
Skin infection
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/29 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
3.6%
1/28 • Number of events 1 • From informed consent until the end of the study.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Injury, poisoning and procedural complications
Skin wound
|
0.00%
0/29 • From informed consent until the end of the study.
|
3.7%
1/27 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Gastrointestinal disorders
Frequent bowel movements
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Gastrointestinal disorders
Nausea
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.4%
1/29 • Number of events 1 • From informed consent until the end of the study.
|
0.00%
0/27 • From informed consent until the end of the study.
|
0.00%
0/28 • From informed consent until the end of the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The employees of the Medicines Evaluation shall not be permitted to present at symposia, national or regional professional meetings, and to publish in journals, theses or dissertations, or otherwise of their own choosing, methods and results of the Clinical Trial subject to the publication policy described in the Protocol without prior written approval of the Sponsor.
- Publication restrictions are in place
Restriction type: OTHER