Trial Outcomes & Findings for NAC Phase IIB: A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients (NCT NCT00809094)
NCT ID: NCT00809094
Last Updated: 2013-04-22
Results Overview
(change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)
COMPLETED
PHASE2
70 participants
From enrollment to end of the 24-week trial
2013-04-22
Participant Flow
Recruitment began 11/4/2008. Recruitment process was staggered: Stanford cohort first to focus on safety data related to potential pulmonary hypertension. After half of the Stanford cohort reached the 8-week time point, the DSMC evaluated PH safety data. The other sites then began enrollment. Final subject enrolled on 2/2011.
Participant milestones
| Measure |
Study Drug
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
34
|
|
Overall Study
COMPLETED
|
36
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Study Drug
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
NAC Phase IIB: A Multi-Center, Phase IIB, Randomized, Placebo-controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine On Redox Changes and Lung Inflammation In Cystic Fibrosis Patients
Baseline characteristics by cohort
| Measure |
Study Drug
n=36 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=34 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
27 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From enrollment to end of the 24-week trialPopulation: The primary endpoint analyses described uses the subset of the ITT population with complete case data. 70 subjects randomized, 65 completed the Week 12 visit and 62 completed the study. There were 6 withdrawals in the NAC group and 2 in Placebo. Five out of 6 subjects in the NAC group withdrew due to subject decision. Missing data was not imputed.
(change in log10 HNE in the active treatment group) - (change in log10 HNE in the placebo group)
Outcome measures
| Measure |
Study Drug
n=26 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=30 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Change in the Logarithm of the Level of Human Neutrophil Elastase (HNE) Activity Measured in Sputum
|
0.03 log10 mcg/mL
Interval -1.12 to 1.38
|
-0.17 log10 mcg/mL
Interval -1.2 to 0.67
|
SECONDARY outcome
Timeframe: From enrollment to the end of the 24-week trialPopulation: Out of 70 subjects randomized, 65 completed the Week 12 visit and 62 completed the study. There were 6 withdrawals in the NAC group and 2 in Placebo. Five out of 6 subjects in the NAC group withdrew due to subject decision. Missing data was not imputed.
Change in forced expiratory volume in 1 second as compared to normals for age (percent of predicted)
Outcome measures
| Measure |
Study Drug
n=30 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=32 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Change in FEV1 (Percent of Predicted for Age)
|
1.055 percent of predicted vlaues
Interval -26.16 to 25.73
|
-5.62 percent of predicted vlaues
Interval -24.54 to 19.69
|
SECONDARY outcome
Timeframe: Baseline to end of study (24 weeks)Population: Out of 70 subjects randomized, 65 completed the Week 12 visit and 62 completed the study. There were 6 withdrawals in the NAC group and 2 in Placebo. Five out of 6 subjects in the NAC group withdrew due to subject decision. Missing data was not imputed.
Forced expiratory volume in 1 second (Liters)
Outcome measures
| Measure |
Study Drug
n=30 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=32 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
FEV1 (L)
|
2.5 Liter
Interval -21.92 to 30.28
|
-4.35 Liter
Interval -25.0 to 22.94
|
SECONDARY outcome
Timeframe: Baseline to end of study (24 weeks)Population: Out of 70 subjects randomized, 65 completed the Week 12 visit and 62 completed the study. There were 6 withdrawals in the NAC group and 2 in Placebo. Five out of 6 subjects in the NAC group withdrew due to subject decision. Missing data was not imputed.
Difference in mid-expiratory flow rates between 25 to 75% of the vital capacity, in L/sec measured at the beginning of the study to the end of the study.
Outcome measures
| Measure |
Study Drug
n=30 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=32 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
FEF 25-75% (L/Sec)
|
0.08 L/sec
Interval -0.39 to 0.88
|
-0.13 L/sec
Interval -1.22 to 0.39
|
SECONDARY outcome
Timeframe: Baseline to 24 weeksPopulation: Out of 70 subjects randomized, 65 completed the Week 12 visit and 62 completed the study. There were 6 withdrawals in the NAC group and 2 in Placebo. Five out of 6 subjects in the NAC group withdrew due to subject decision. Missing data was not imputed.
Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to the end of study (24 weeks).
Outcome measures
| Measure |
Study Drug
n=30 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=32 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
FEF 25-75% (Percent of Predicted)
|
1.33 percent of predicted
Interval -16.46 to 25.32
|
-3.81 percent of predicted
Interval -25.2 to 9.78
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 24 weeksPopulation: Sixteen subjects at Stanford University were enrolled as an initial safety cohort, and their data was used to evaluate the potential for NAC to cause PH in CF subjects.
Change in the diffusing capacity of carbon monoxide across the lung measured from baseline to end of 24-week study.
Outcome measures
| Measure |
Study Drug
n=8 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=8 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Change in DLCO (ml/Min/mmHg) Over Time by Treatment Group
|
-0.32 ml/min/mm Hg
Standard Deviation 2.86 • Interval -4.76 to
|
-1.39 ml/min/mm Hg
Standard Deviation 3.93
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 24 weeksPopulation: Sixteen subjects at Stanford University were enrolled as an initial safety cohort, and their data was used to evaluate the potential for NAC to cause PH in CF subjects. 1 subject in NAC cohort has missing data. It was not imputed
Change in measure of estimated right ventricular pressure over the 24-week study period
Outcome measures
| Measure |
Study Drug
n=7 Participants
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=8 Participants
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Change in ECHO Tricuspid Regurgitation (mm Hg) Over Time by Treatment Group
|
31.5 mm Hg
Standard Deviation 6.02
|
31.75 mm Hg
Standard Deviation 5.84
|
Adverse Events
Study Drug
Placebo
Serious adverse events
| Measure |
Study Drug
n=36 participants at risk
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=34 participants at risk
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Exacerbation
|
41.7%
15/36
|
50.0%
17/34
|
Other adverse events
| Measure |
Study Drug
n=36 participants at risk
N-acetylcysteine (NAC) :PharmaNAC® 900 mg effervescent tablets in blister packs were supplied by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada).
|
Placebo
n=34 participants at risk
Identically packaged effervescent tablets that contained only the carrier were provided in blister packs by BioAdvantex Pharma, Inc. (Mississauga, ON, Canada)
|
|---|---|---|
|
General disorders
Fatigue
|
36.1%
13/36 • Number of events 17
|
23.5%
8/34 • Number of events 21
|
|
Investigations
Forced Expiratory Volume Decreased
|
25.0%
9/36 • Number of events 11
|
26.5%
9/34 • Number of events 14
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
5.6%
2/36 • Number of events 2
|
14.7%
5/34 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
11.1%
4/36 • Number of events 5
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
4/36 • Number of events 5
|
8.8%
3/34 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
13.9%
5/36 • Number of events 6
|
5.9%
2/34 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
3/36 • Number of events 4
|
11.8%
4/34 • Number of events 4
|
|
General disorders
Chest Discomfort
|
8.3%
3/36 • Number of events 5
|
14.7%
5/34 • Number of events 7
|
|
General disorders
Non-cardiac Chest Pain
|
0.00%
0/36
|
8.8%
3/34 • Number of events 3
|
|
General disorders
Pain
|
8.3%
3/36 • Number of events 5
|
5.9%
2/34 • Number of events 3
|
|
General disorders
Pyrexia
|
11.1%
4/36 • Number of events 7
|
23.5%
8/34 • Number of events 14
|
|
Infections and infestations
sinusitis
|
8.3%
3/36 • Number of events 3
|
2.9%
1/34 • Number of events 1
|
|
Investigations
Pulmonary function test decreased
|
5.6%
2/36 • Number of events 3
|
8.8%
3/34 • Number of events 3
|
|
Investigations
Weight decreased
|
13.9%
5/36 • Number of events 6
|
14.7%
5/34 • Number of events 6
|
|
Investigations
white blood cell count increased
|
5.6%
2/36 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.6%
2/36 • Number of events 5
|
8.8%
3/34 • Number of events 3
|
|
Nervous system disorders
Sinus headache
|
11.1%
4/36 • Number of events 18
|
11.8%
4/34 • Number of events 6
|
|
Psychiatric disorders
Anxiety
|
5.6%
2/36 • Number of events 4
|
0.00%
0/34
|
|
Renal and urinary disorders
Nephrolitiasis
|
8.3%
3/36 • Number of events 3
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
61.1%
22/36 • Number of events 55
|
61.8%
21/34 • Number of events 45
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
13.9%
5/36 • Number of events 7
|
5.9%
2/34 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
22.2%
8/36 • Number of events 12
|
17.6%
6/34 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.6%
2/36 • Number of events 2
|
29.4%
10/34 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
13.9%
5/36 • Number of events 5
|
29.4%
10/34 • Number of events 16
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
8.3%
3/36 • Number of events 5
|
2.9%
1/34 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
8.3%
3/36 • Number of events 4
|
2.9%
1/34 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
22.2%
8/36 • Number of events 10
|
38.2%
13/34 • Number of events 18
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
19.4%
7/36 • Number of events 10
|
23.5%
8/34 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
19.4%
7/36 • Number of events 8
|
14.7%
5/34 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
11.1%
4/36 • Number of events 6
|
17.6%
6/34 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
11.1%
4/36 • Number of events 5
|
11.8%
4/34 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
11.1%
4/36 • Number of events 6
|
17.6%
6/34 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.8%
1/36 • Number of events 1
|
5.9%
2/34 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place