Trial Outcomes & Findings for Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients (NCT NCT00677365)
NCT ID: NCT00677365
Last Updated: 2024-12-27
Results Overview
Patients were required to cough deeply and then spit sputum into a sterile container. The bacteria contained in the sputum sample was incubated in a laboratory and the number of P. aeruginosa colony forming units per gram of sputum (CFU/g) was determined. The difference in CFUs/g were then compared from baseline to the conclusion of the 28 day treatment period
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
151 participants
Primary outcome timeframe
from baseline to end of treatment (28 days)
Results posted on
2024-12-27
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo Group
|
MP-376 120 mg QD
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
37
|
38
|
37
|
39
|
|
Overall Study
COMPLETED
|
35
|
37
|
35
|
36
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
2
|
3
|
Reasons for withdrawal
| Measure |
Placebo
Placebo Group
|
MP-376 120 mg QD
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Overall Study
Other reason
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Safety, Tolerability and Efficacy of MP-376 Given for 28 Days to Cystic Fibrosis (CF) Patients
Baseline characteristics by cohort
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
Total
n=151 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
30.1 years
STANDARD_DEVIATION 9.94 • n=5 Participants
|
28.0 years
STANDARD_DEVIATION 6.86 • n=7 Participants
|
27.5 years
STANDARD_DEVIATION 9.05 • n=5 Participants
|
29.2 years
STANDARD_DEVIATION 9.98 • n=4 Participants
|
28.7 years
STANDARD_DEVIATION 9.02 • n=21 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
85 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
124 Participants
n=21 Participants
|
|
Region of Enrollment
Europe
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: from baseline to end of treatment (28 days)Population: Modified Intent-to-Treat (MITT; patients who received at least one dose of study drug)
Patients were required to cough deeply and then spit sputum into a sterile container. The bacteria contained in the sputum sample was incubated in a laboratory and the number of P. aeruginosa colony forming units per gram of sputum (CFU/g) was determined. The difference in CFUs/g were then compared from baseline to the conclusion of the 28 day treatment period
Outcome measures
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Change in P. Aeruginosa Density
|
0.23 log10 CFU/g sputum
Standard Error 0.220
|
-0.31 log10 CFU/g sputum
Standard Error 0.227
|
-0.31 log10 CFU/g sputum
Standard Error 0.220
|
-0.73 log10 CFU/g sputum
Standard Error 0.222
|
SECONDARY outcome
Timeframe: from baseline until final study visit (up to 56 days)Population: MITT
Time to administration of other anti-pseudomonal antimicrobials in patients with at least one of the following: decreased exercise tolerance, increased cough, increased sputum/chest congestion, or decreased appetite; 25th percentile data reported
Outcome measures
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Time to Administration of Other Anti-pseudomonal Antimicrobials
|
31 days
Interval 29.0 to 43.0
|
NA days
Interval 32.0 to
Not available; 25th percentile was not reached within the 56-day study duration
|
56 days
Interval 43.0 to
Not available; The upper range of the confidence interval exceeds the 56-day study duration
|
59 days
Interval 57.0 to
Not available; The upper range of the confidence interval exceeds the 56-day study duration
|
SECONDARY outcome
Timeframe: from baseline to end of the 28-day treatment period (28 days)Population: MITT
Percent change in the amount of air the patient could exhale in 1 second
Outcome measures
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Percent Change in Forced Expiratory Volume in 1 Second (FEV1)
|
-2.36 Percent change
Standard Error 2.085
|
1.93 Percent change
Standard Error 2.114
|
2.56 Percent change
Standard Error 2.077
|
6.25 Percent change
Standard Error 2.081
|
SECONDARY outcome
Timeframe: from baseline to the end of the treatment 28-day treatment period (28 days)Population: MITT
Change in the predicted percent of air the patient could exhale in one second
Outcome measures
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Change in FEV1 Percent Predicted
|
-2.39 Percent
Standard Error 2.370
|
1.96 Percent
Standard Error 2.402
|
3.10 Percent
Standard Error 2.361
|
8.55 Percent
Standard Error 2.358
|
SECONDARY outcome
Timeframe: from baseline to the end of the 28-day treatment period (28 days)Population: MITT
Change in the score from 0 to 100 that a patient reports for their respiratory symptoms in the CFQ-R. An increase in score illustrates an improvement in symptoms. An increase of 4 or more is considered clinically significant
Outcome measures
| Measure |
Placebo
n=37 Participants
Placebo Group
|
MP-376 120 mg QD
n=38 Participants
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 Participants
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 Participants
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Changes in Respiratory Domain Scores of Cystic Fibrosis Questionnaire - Revised (CFQ-R)
|
-0.44 units on a scale
Standard Error 2.715
|
2.00 units on a scale
Standard Error 2.728
|
0.31 units on a scale
Standard Error 2.689
|
4.06 units on a scale
Standard Error 2.690
|
SECONDARY outcome
Timeframe: from baseline until the end of the 28-day treatment period (28 days)Population: MITT
All isolates of P. aeruginosa cultures grown from patient sputum samples were evaluated to see whether the minimum concentration of levofloxacin needed to inhibit growth of the bacteria (i.e., minimum inhibitory concentration; MIC) had increased; 2. The MIC50 and MIC90 values were calculated as the 50th percentile value and the 90th percentile value, respectively. Note that percentile values between dilution values were rounded up to the nearest dilution value
Outcome measures
| Measure |
Placebo
n=140 Isolates
Placebo Group
|
MP-376 120 mg QD
n=152 Isolates
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=148 Isolates
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=152 Isolates
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Changes in Susceptability Patterns of Isolated Organisms
Baseline Minimum Inhibitory Concentration (MIC)50
|
4 ug/mL
|
4 ug/mL
|
4 ug/mL
|
4 ug/mL
|
|
Changes in Susceptability Patterns of Isolated Organisms
Day 28 MIC for 50% (MIC50)
|
4 ug/mL
|
4 ug/mL
|
4 ug/mL
|
4 ug/mL
|
|
Changes in Susceptability Patterns of Isolated Organisms
Baseline MIC for 90% (MIC90)
|
16 ug/mL
|
32 ug/mL
|
16 ug/mL
|
16 ug/mL
|
|
Changes in Susceptability Patterns of Isolated Organisms
Day 28 MIC90
|
8 ug/mL
|
16 ug/mL
|
16 ug/mL
|
32 ug/mL
|
Adverse Events
Placebo
Serious events: 4 serious events
Other events: 28 other events
Deaths: 0 deaths
MP-376 120 mg QD
Serious events: 1 serious events
Other events: 33 other events
Deaths: 0 deaths
MP-376 240 mg QD
Serious events: 4 serious events
Other events: 32 other events
Deaths: 0 deaths
MP-376 240 mg BID
Serious events: 4 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=37 participants at risk
Placebo Group
|
MP-376 120 mg QD
n=38 participants at risk
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 participants at risk
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 participants at risk
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
General disorders
Disease progression
|
8.1%
3/37 • Number of events 3
|
0.00%
0/38
|
10.8%
4/37 • Number of events 4
|
7.7%
3/39 • Number of events 3
|
|
Infections and infestations
Appendicitis
|
0.00%
0/37
|
2.6%
1/38 • Number of events 1
|
0.00%
0/37
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
2.7%
1/37 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
0.00%
0/39
|
|
Infections and infestations
Pneumonia
|
0.00%
0/37
|
0.00%
0/38
|
0.00%
0/37
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
2.7%
1/37 • Number of events 1
|
0.00%
0/38
|
0.00%
0/37
|
0.00%
0/39
|
Other adverse events
| Measure |
Placebo
n=37 participants at risk
Placebo Group
|
MP-376 120 mg QD
n=38 participants at risk
MP-376 120 mg Once Daily (QD) Group
|
MP-376 240 mg QD
n=37 participants at risk
MP-376 240 mg Once Daily (QD) Group
|
MP-376 240 mg BID
n=39 participants at risk
MP-376 240 mg Twice Daily (BID) Group
|
|---|---|---|---|---|
|
Nervous system disorders
Dysgeusia
|
2.7%
1/37 • Number of events 1
|
36.8%
14/38 • Number of events 15
|
48.6%
18/37 • Number of events 19
|
33.3%
13/39 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.2%
6/37 • Number of events 7
|
23.7%
9/38 • Number of events 9
|
27.0%
10/37 • Number of events 12
|
25.6%
10/39 • Number of events 11
|
|
General disorders
Disease progression
|
27.0%
10/37 • Number of events 12
|
10.5%
4/38 • Number of events 4
|
21.6%
8/37 • Number of events 9
|
17.9%
7/39 • Number of events 7
|
|
Nervous system disorders
Headache
|
0.00%
0/37
|
18.4%
7/38 • Number of events 8
|
5.4%
2/37 • Number of events 2
|
10.3%
4/39 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
18.9%
7/37 • Number of events 9
|
7.9%
3/38 • Number of events 3
|
13.5%
5/37 • Number of events 6
|
5.1%
2/39 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
10.8%
4/37 • Number of events 4
|
7.9%
3/38 • Number of events 3
|
8.1%
3/37 • Number of events 3
|
5.1%
2/39 • Number of events 2
|
|
General disorders
Pyrexia
|
8.1%
3/37 • Number of events 3
|
0.00%
0/38
|
5.4%
2/37 • Number of events 2
|
15.4%
6/39 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal pain
|
2.7%
1/37 • Number of events 1
|
5.3%
2/38 • Number of events 2
|
5.4%
2/37 • Number of events 2
|
7.7%
3/39 • Number of events 3
|
|
General disorders
Chest Discomfort
|
8.1%
3/37 • Number of events 3
|
0.00%
0/38
|
5.4%
2/37 • Number of events 2
|
10.3%
4/39 • Number of events 5
|
|
Infections and infestations
Nasopharyngitis
|
8.1%
3/37 • Number of events 3
|
2.6%
1/38 • Number of events 1
|
8.1%
3/37 • Number of events 4
|
7.7%
3/39 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhea
|
5.4%
2/37 • Number of events 2
|
5.3%
2/38 • Number of events 2
|
10.8%
4/37 • Number of events 4
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
2.7%
1/37 • Number of events 1
|
7.9%
3/38 • Number of events 3
|
2.7%
1/37 • Number of events 1
|
7.7%
3/39 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
2.7%
1/37 • Number of events 1
|
5.3%
2/38 • Number of events 2
|
5.4%
2/37 • Number of events 2
|
5.1%
2/39 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place