Trial Outcomes & Findings for Safety and Efficacy of Two Different Doses of Asacol in the Treatment of Moderately Active Ulcerative Colitis (NCT NCT00073021)

Results Overview

Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment \[stool frequency, rectal bleeding, PFA, sigmoidoscopy\] and no worsening in any other clinical assessments)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

386 participants

Primary outcome timeframe

6 Weeks

Results posted on

2015-06-29

Participant Flow

Recruitment began Feb. 28, 2001. Randomized 386 patients of which 117 had mild disease and 268 had moderate disease at baseline. Analysis only includes patients with moderate disease at baseline.

Participant milestones

Participant milestones
Measure	Asacol 2.4 g/Day Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Overall Study STARTED	139	129
Overall Study COMPLETED	113	113
Overall Study NOT COMPLETED	26	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Asacol 2.4 g/Day Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Overall Study Protocol Violation	2	1
Overall Study Adverse Event	4	4
Overall Study Withdrawal by Subject	6	5
Overall Study Physician Decision	3	1
Overall Study Lack of Efficacy	11	5

Baseline Characteristics

Safety and Efficacy of Two Different Doses of Asacol in the Treatment of Moderately Active Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Asacol 2.4 g/Day n=139 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=129 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).	Total n=268 Participants Total of all reporting groups
Age, Customized 18 - 64 years	126 Participants n=5 Participants	118 Participants n=7 Participants	244 Participants n=5 Participants
Age, Customized >= 65 years	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	75 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	54 Participants n=7 Participants	116 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	108 Participants n=5 Participants	96 Participants n=7 Participants	204 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Indian)	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Oriental)	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	16 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Multi-racial/other	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Weeks

Population: ITT Population with Moderate Disease \[PGA = 2\] at Baseline

Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment \[stool frequency, rectal bleeding, PFA, sigmoidoscopy\] and no worsening in any other clinical assessments)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Treatment Success Patients at Week 6, ITT (Intent to Treat) Population	59.2 Percentage of Participants	71.8 Percentage of Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT Population with Moderate Disease \[PGA = 2\] at Baseline.

UCDAI - sum of clinical assessment scores (stool frequency score \[0=normal, 1=1-2 stools \> normal/day, 2=3-4 stools \> normal/day, 3=5 or more stools \> normal/day\], rectal bleeding score \[0=no blood seen, 1=streaks of blood with stool less than half of the time, 2=obvious blood with stool most of the time, 3=blood alone passed and PGA score \[0=quiescent disease, 1=mild, 2=moderate, 3=severe\]) and sigmoidoscopy score \[0=normal, 1=mild, 2=moderate, 3=severe\]

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Change From Baseline in Ulcerative Colitis Disease Activity Index (UCDAI) at Week 6, ITT Population	-3.2 Scores on a Scale Standard Error 0.27	-3.7 Scores on a Scale Standard Error 0.27

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Patients with Moderate Disease \[PGA=2\] at Baseline. Percentage of patients whose rectal bleeding AND sigmoidoscopy scores BOTH improved from baseline at Week 6

Rectal Bleeding - 0=no blood seen, 1=streaks of blood w/stool less than half of the time, 2=obvious blood w/stool most of the time, 3=blood alone passed Sigmoidoscopy Assessment Score - 0=normal (intact vascular pattern, no friability or granularity), 1=mild (erythema, diminished or absent vascular markings; mild granularity; friability), 2=moderate (marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations) 3=severe (spontaneous bleeding, ulcerations)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Participants Whose Rectal Bleeding & Sigmoidoscopy Score Both Improved From Baseline to Week 6, ITT Population	59.8 Percentage of Participants	63.6 Percentage of Participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Population with Moderate Disease \[PGA=2\] at Baseline

Sigmoidoscopy Assessment Score (0=normal intact vascular pattern, no friability or granularity, 1=mild erythema; diminished or absent vascular markings; mild granularity; friability, 2=moderate marked erythema, granularity; absent vascular markings; bleeds with minimal trauma; no ulcerations, 3=severe spontaneous bleeding, ulcerations)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients Whose Sigmoidoscopy Score Improved From Baseline to Week 6, ITT Population	69.0 Percentage of Participants	75.2 Percentage of Participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Patients with Moderate Disease \[PGA=2\] at Baseline

0=Normal stool frequency per day, 1=1-2 stools greater than normal per day, 2=3-4 stools greater than normal per day, 3=5 or more stools greater than normal per day

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients With an Improvement in Stool Frequency, ITT Population, Week 6	71.3 Percentage of Participants	74.0 Percentage of Participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Population with Moderate Disease \[PGA=2\] at Baseline

Rectal Bleeding (0=no blood seen, 1=streaks of blood with stool less than half of the time, 2=obvious blood with stool most of the time, 3=blood alone passed)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients With Improvement in Rectal Bleeding, ITT Population, Week 6	77.5 Percentage of Participants	78.5 Percentage of Participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Population with Moderate Disease \[PGA=2\] at Baseline

PFA - 0=generally well, 1=fair, 2=poor, 3=terrible

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients With Improvement in Patient's Functional Assessment (PFA), ITT Population, Week 6	70.5 Percentage of Participants	69.6 Percentage of Participants

SECONDARY outcome

Timeframe: 6 Weeks

Population: ITT Population with Moderate Disease \[PGA=2\] at Baseline

PGA -Physician's Global Assessment - 0=quiescent disease (all parameters 0), 1=mild disease (parameters mostly 1's) 2=moderate (parameters mostly 2's), 3=severe (parameters mostly 3's) \[parameters: combination of stool frequency, rectal bleeding, PFA \& sigmoidoscopy findings\] If scoring equal default to physician judgement.

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients With Improvement in Physician Global Assessment (PGA)Score, ITT Population, Week 6	73.5 Percentage of Participants	83.2 Percentage of Participants

SECONDARY outcome

Timeframe: 3 Weeks

Population: All Randomized Patients with Moderate Disease\[PGA=2\] at Baseline. Questionnaire analyzable if patient answered 28 of 32 for total, 8/10 for bowel, 3/5 for systemic, 10/12 for emotional, 3/5 for social.

IBDQ-32 questions divided into 4 categories: bowel, systemic, emotional and social. Each question graded with the following responses: 1-more than ever before, 2-extremely frequently, 3-very frequently, 4-moderate increase in frequency, 5-some increase in frequency, 6-slight increase in frequency or 7-not at all/normal; 1/worst thru 7/best. Scoring 32 - 224 - higher score better.

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=139 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=129 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 3, All Randomized Patients	30.4 Scores on a Scale Standard Error 2.84	29.8 Scores on a Scale Standard Error 2.60

SECONDARY outcome

Timeframe: 6 Weeks

Population: All Randomized Patients with Moderate Disease \[PGA=2\] at Baseline. Questionnaire analyzable if patient answered 28 of 32 for total, 8/10 for bowel, 3/5 for systemic, 10/12 for emotional, 3/5 for social.

IBDQ-32 questions divided into 4 categories: bowel, systemic, emotional and social. Each question graded with the following responses: 1-more than ever before, 2-extremely frequently, 3-very frequently, 4-moderate increase in frequency, 5-some increase in frequency, 6-slight increase in frequency or 7-not at all/normal; 1/worst thru 7/best. Scoring 32-224 - higher score better.

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=139 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=129 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Mean Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 6, All Randomized Patients	43.1 Scores on a Scale Standard Error 3.5	40.4 Scores on a Scale Standard Error 3.08

SECONDARY outcome

Timeframe: 6 Weeks

Population: All Randomized Patients with Moderate Disease \[PGA=2\] at Baseline. Left Sided Disease = proctitis, proctosigmoiditis or left-sided colitis

Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment \[stool frequency, rectal bleeding, PFA, sigmoidoscopy\] and no worsening in any other clinical assessments)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=105 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=97 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Patients With Moderate, Left-Sided Disease at Baseline Classified as Treatment Success at Week 6, All Randomized Patients	60.0 Percentage of Participants	71.1 Percentage of Participants

SECONDARY outcome

Timeframe: 3 Weeks

Population: ITT Patients with Moderate Disease \[PGA = 2\] at Baseline

Treatment success defined as complete response (PGA score 0 and complete resolution of stool frequency, rectal bleeding, PFA (patient's functional assessment), normal sigmoidoscopy) or partial response (improvement from baseline PGA and improvement in 1 clinical assessment \[stool frequency, rectal bleeding, PFA, sigmoidoscopy\] and no worsening in any other clinical assessments)

Outcome measures

Outcome measures
Measure	Asacol 2.4 g/Day n=130 Participants Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=124 Participants Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Percentage of Treatment Success Patients at Week 3, ITT Population	51.5 Percentage of Participants	61.3 Percentage of Participants

Adverse Events

Asacol 2.4 g/Day

Serious events: 4 serious events

Other events: 72 other events

Deaths: 0 deaths

Asacol 4.8 g/Day

Serious events: 1 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Asacol 2.4 g/Day n=195 participants at risk；n=139 participants at risk Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=191 participants at risk；n=129 participants at risk Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Hepatobiliary disorders Cholecystitis	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Nausea	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Vomiting	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Increased Diarrhea	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Abdominal Cramping	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Exacerbation of Ulcerative Colitis	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Renal and urinary disorders Nephritis	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Pancreatitis	0.72% 1/139 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.00% 0/129 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Musculoskeletal and connective tissue disorders Shoulder/Chest Pain	0.00% 0/139 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.78% 1/129 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Cardiac disorders Pericarditis	0.00% 0/139 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.78% 1/129 • Number of events 1 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004

Other adverse events

Additional Information

Grexan Wulff, Manager Regulatory Affairs

Warner Chilcott

Phone: 973-442-3376

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Asacol 2.4 g/Day n=195 participants at risk；n=139 participants at risk Two 400 mg Asacol tablets and 2 placebo tablets (matching 800 mg formulation) taken 3 times daily (morning, midday, evening).	Asacol 4.8 g/Day n=191 participants at risk；n=129 participants at risk Two 800 mg Asacol tablets and 2 placebo tablets (matching 400 mg formulation) taken 3 times daily (morning, midday, evening).
Nervous system disorders Headache	7.7% 15/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	8.4% 16/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Pain, Abdominal	5.6% 11/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	3.7% 7/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Infections and infestations Infection	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	4.7% 9/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Respiratory, thoracic and mediastinal disorders Rhinitis	3.6% 7/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.52% 1/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Diarrhea	3.1% 6/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	4.2% 8/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Nausea	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.6% 5/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Rectal Disorder	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.6% 5/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Dyspepsia	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.1% 4/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Infections and infestations Flu Syndrome	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.1% 4/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Colitis Ulcer	1.5% 3/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.6% 5/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
General disorders Fever	2.1% 4/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.1% 4/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Gastrointestinal disorders Flatulence	3.1% 6/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	1.0% 2/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
General disorders Asthenia	1.5% 3/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.1% 4/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Respiratory, thoracic and mediastinal disorders Cough Increased	3.1% 6/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.52% 1/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Skin and subcutaneous tissue disorders Rash	2.1% 4/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	1.0% 2/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Respiratory, thoracic and mediastinal disorders Sinusitis	2.6% 5/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	0.52% 1/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004
Respiratory, thoracic and mediastinal disorders Bronchitis	0.51% 1/195 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004	2.1% 4/191 • 6 week treatment period for each subject, February 28, 2001 thru April 15 2004