Study to Assess the Efficacy and Safety of BDP HFA Nasal... | NCT00854360

Study to Assess the Efficacy and Safety of BDP HFA Nasal... | NCT00854360 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BDP HFA 80 µg/day	Experimental	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 micrograms (µg) BDP HFA and two actuations of placebo HFA once daily.	Drug: Beclomethasone dipropionate HFA Nasal Aerosol Drug: Placebo
BDP HFA 160 µg/day	Experimental	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.	Drug: Beclomethasone dipropionate HFA Nasal Aerosol
BDP HFA 320 µg/day	Experimental	During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily.	Drug: Beclomethasone dipropionate HFA Nasal Aerosol
Placebo	Placebo Comparator	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Beclomethasone dipropionate HFA Nasal Aerosol	Drug	Beclomethasone dipropionate (BDP) Hydrofluoroalkane (HFA) Nasal Aerosol	BDP HFA 160 µg/day BDP HFA 320 µg/day

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period	Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 12 hours twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.	Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period	Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the 10 minutes prior to the assessment, twice daily (AM & PM) using the following scale: 0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Male or female patients 12 years of age and older, as of the Screening Visit (SV).
General good health, and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study.
A history of SAR to relevant seasonal allergen (tree/grass pollen) for a minimum of two years immediately preceding the study Screening Visit (SV). The SAR must have been of sufficient severity to have required treatment (either continuous or intermittent) in the past and in the investigator's judgment is expected to be exposed to the allergen and require treatment throughout the entire study period.
A demonstrated sensitivity to relevant tree/grass pollen known to produce SAR through a standard skin prick test. A positive test is defined as a wheal diameter at least 3 mm larger than the control wheal for the skin prick test. Documentation of a positive result within 12 months prior to Screening Visit (SV) is acceptable.
Other criteria apply

Key Exclusion Criteria:

Participation in any investigational drug study within the 30 days preceding the Screening Visit (SV) or planned participation in another investigational drug study at any time during this study.
History of physical findings of nasal pathology, including nasal polyps or other clinically significant respiratory tract malformations, recent nasal biopsy, nasal trauma or surgery, atrophic rhinitis, or rhinitis medicamentosa (all within the last 60 days prior to the SV).
History of a respiratory infection or disorder [including, but not limited to bronchitis, pneumonia, chronic sinusitis, influenza, severe acute respiratory syndrome (SARS)] within the 14 days preceding the Screening Visit (SV), or development of a respiratory infection during the Run-in Period.
Use of any prohibited concomitant medications within the prescribed (per protocol) time since the last dosing period prior to the Screening Visit (SV) and/or plans for use during the entire treatment duration.
Other criteria apply

Contacts/Locations Module

Name	Affiliation	Role
Sudeesh Tantry, Ph.D.	Teva Branded Pharmaceutical Products R&D, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Teva Global Respiratory Research Study Site		Mission Viejo	California	92691	United States
Teva Global Respiratory Research Study Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23815103	Derived	Raphael GD, Berger WE, Prenner BM, Finn AF Jr, Kelley L, Tantry SK. Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults. Curr Med Res Opin. 2013 Oct;29(10):1329-40. doi: 10.1185/03007995.2013.821055. Epub 2013 Aug 6.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 micrograms (µg) beclomethasone dipropionate (BDP) hydrofluoroalkane (HFA) and two actuations of placebo HFA once daily.
FG001	BDP HFA 160 µg/Day

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0011 subjects FG0022 subjects FG0036 subjects
Withdrawal by Subject		FG0000 subjects FG0010 subjects FG0020 subjects FG0031 subjects
Pregnancy		FG0000 subjects FG0011 subjects FG0020 subjects FG0030 subjects
Lack of Efficacy		FG0002 subjects FG0011 subjects FG0020 subjects FG0030 subjects
Other		FG0000 subjects FG0010 subjects FG0020 subjects FG0033 subjects

Arm/Group Information

ID	Title	Description
BG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
BG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.
BG002	BDP HFA 320 µg/Day	During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily.
BG003	Placebo	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Demographic data are provided for the Intent to Treat population.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00037.6± 13.86 BG00139.8± 15.26 BG00238.5± 14.74 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00076 BG00186 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG00092 BG00199 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG00014 BG00110 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000118 BG001123 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Average AM and PM Reflective Total Nasal Symptom Score (rTNSS) Over the Two-week Treatment Period

Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 12 hours twice daily (AM & PM) using the following scale:

0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptoms hard to tolerate, interfere with daily activities and/or sleeping).

The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

The Intent-to-treat population included all randomized patients who received at least one dose of randomized study medication and had at least one post-baseline assessment.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.
OG002	BDP HFA 320 µg/Day	During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily.
OG003	Placebo	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily.

Units	Counts
Participants	OG000118 OG001123 OG002122 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.88± 0.18 OG001-1.87± 0.18 OG002-2.22± 0.18 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.255	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.29	Standard Error of the Mean	0.26	2-Sided	95	-0.80	0.21				No

Secondary

Change From Baseline in Average AM and PM Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two Week Treatment Period

Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the 10 minutes prior to the assessment, twice daily (AM & PM) using the following scale:

0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities and/or sleeping). The total nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

Intent to treat population.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.
OG002	BDP HFA 320 µg/Day

Secondary

Change From Baseline in Morning Instantaneous Total Nasal Symptom Score (iTNSS) Over the Two-week Treatment Period

Change from Baseline in the morning patient-reported instantaneous TNSS. Participants recorded the severity of their nasal symptoms (sneezing, runny nose, itchy nose and nasal congestion) over the past 10 minutes (prior to the assessment) in the morning on a scale from 0 (mild symptoms) to 3 (severe symptoms). The total nasal symptom score (sum of the 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

Intent to treat population.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.
OG002	BDP HFA 320 µg/Day	During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily.

Secondary

Change From Baseline in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)

The adult RQLQ has 28 questions in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional). Participants were asked to recall their experiences during the previous week and to give their responses on a 7-point scale (0 = Least severe to 6 = Extremely severe). The overall RQLQ score is the mean of all 28 responses, and ranges from 0 to 7. A negative change from Baseline score indicates symptom improvement.

The RQLQ population included only those participants over the age of 18 years with an impaired quality of life at Baseline as defined by a RQLQ score at the Randomization Visit of 3.0 or greater.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and Week 2

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.
OG002	BDP HFA 320 µg/Day

Secondary

Change From Baseline in Morning 24-hour Reflective Ocular Symptom Score Over the Two-week Treatment Period

Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes and redness of eyes) for the past 24 hours each morning using the following scale:

0=absent (no sign/symptoms); 1=mild (sign/symptom present, minimal awareness, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (sign/symptom hard to tolerate, interfere with daily activities or sleeping).

The total ocular symptom score (sum of 3 symptom scores) ranges from 0 to 9 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

The ocular population included only those participants with adequate ocular symptoms during the Run-in Period as defined by a mean daily 24-hour reflective score of 4 or greater for the 24-hour reflective ocular symptom score, over the last 7 days of the Run-in Period.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.

Secondary

Change From Baseline in Morning 24-hour Reflective Non-nasal Symptom Score Over the Two-week Treatment Period

Participants recorded the severity of their symptoms (itching/burning eyes, tearing/watering eyes, redness of eyes and itching of ears or palate) for the past 24 hours each morning using the following scale:

0=absent (no sign/symptom); 1=mild (sign/symptom present, easily tolerated); 2=moderate (awareness of sign/symptom, bothersome but tolerable); 3=severe (symptoms hard to tolerate, interfere with daily activities or sleeping).

Total non-nasal symptom score (sum of 4 symptom scores) ranges from 0 to 12 (worst symptoms). A negative change from Baseline score indicates symptom improvement.

The non-nasal population included only those participants with adequate non-nasal symptoms during the Run-in Period as defined by a mean daily 24-hour reflective score of 6 or greater for the 24-hour reflective non-nasal symptom score, over the last 7 days of the Run-in Period.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -6 to 0) and Days 1-15 (2-week Treatment Period)

ID	Title	Description
OG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.
OG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BDP HFA 80 µg/Day	During the 2-week double-blind Treatment Period participants self-administered two actuations (one per nostril) of 40 (µg) BDP HFA and two actuations of placebo HFA once daily.	0	118	6	118
EG001	BDP HFA 160 µg/Day	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of 40 µg BDP HFA once daily.	2	123	3	123
EG002	BDP HFA 320 µg/Day	During the 2-week double-blind Treatment Period participants self-administered 4 actuations (two per nostril) of 80 µg BDP HFA once daily.	0	122	3	122
EG003	Placebo	During the 2-week double-blind Treatment Period participants self-administered four actuations (two per nostril) of placebo HFA once daily.	0	123	1	123

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 11.1	Systematic Assessment		EG0000 affected118 at risk EG0011 affected123 at risk EG0020 affected122 at risk EG0030 affected123 at risk
Abortion spontaneous incomplete	Pregnancy, puerperium and perinatal conditions	MedDRA 11.1	Non-systematic Assessment		EG0000 affected118 at risk EG0011 affected123 at risk EG0020 affected122 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment		EG0006 affected118 at risk EG0013 affected123 at risk EG0023 affected122 at risk EG0031 affected123 at risk

Ancestor Terms

ID	Term
D065631	Rhinitis, Allergic
D012220	Rhinitis
D009668	Nose Diseases
D012140	Respiratory Tract Diseases
D012130	Respiratory Hypersensitivity
D010038	Otorhinolaryngologic Diseases
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.278	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.27	Standard Error of the Mean	0.25	2-Sided	95	-0.77	0.22	No	Superiority or Other
OG001 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.385	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.22	Standard Error of the Mean	0.25	2-Sided	95	-0.70	0.27	No	Superiority or Other
OG002 OG003	A priori threshold for statistical significance is p<0.05.	Repeated Measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.016	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.60	Standard Error of the Mean	0.25	2-Sided	95	-1.09	-0.11	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.082	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.45	Standard Error of the Mean	0.26	2-Sided	95	-0.95	0.06	No	Superiority or Other
OG001 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.114	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.40	Standard Error of the Mean	0.25	2-Sided	95	-0.90	0.10	No	Superiority or Other
OG002 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.001	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.83	Standard Error of the Mean	0.26	2-Sided	95	-1.33	-0.33	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	A priori threshold for statistical significance is p<0.05.	ANCOVA	Results obtained from ANCOVA with treatment, baseline and center in the model.	0.747	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.07	Standard Error of the Mean	0.23	2-Sided	95	-0.52	0.37	No	Superiority or Other
OG001 OG003	A priori threshold for statistical significance is p<0.05.	ANCOVA	Results obtained from ANCOVA with treatment, baseline and center in the model.	0.605	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.11	Standard Error of the Mean	0.21	2-Sided	95	-0.53	0.31	No	Superiority or Other
OG002 OG003	A priori threshold for statistical significance is p<0.05.	ANCOVA	Results obtained from ANCOVA with treatment, baseline and center in the model.	0.083	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.39	Standard Error of the Mean	0.23	2-Sided	95	-0.84	0.05	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.989	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.00	Standard Error of the Mean	0.23	2-Sided	95	-0.45	0.46	No	Superiority or Other
OG001 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.808	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.06	Standard Error of the Mean	0.23	2-Sided	95	-0.39	0.50	No	Superiority or Other
OG002 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.195	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.29	Standard Error of the Mean	0.23	2-Sided	95	-0.74	0.15	No	Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.903	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	0.04	Standard Error of the Mean	0.31	2-Sided	95	-0.64	0.57	No	Superiority or Other
OG001 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.952	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	0.02	Standard Error of the Mean	0.31	2-Sided	95	-0.58	0.62	No	Superiority or Other
OG002 OG003	A priori threshold for statistical significance is p<0.05.	Repeated measures ANCOVA	The repeated measures ANCOVA included covariate adjustment for baseline, day, treatment, and the treatment by day interaction.	0.187	A multiplicity adjustment procedure was implemented which allowed for control of the Type I error within a particular treatment comparison, as well as within a particular endpoint, however it did not control the overall Type I error.	LS Mean Difference	-0.40	Standard Error of the Mean	0.30	2-Sided	95	-0.99	0.19	No	Superiority or Other