A Study of the Equivalent Effectiveness of 400 mcg Mometasone Furoate Using Two Different Dry Powder Inhalers in Moderate Asthmatics (Study P04828)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00521599
• Collaborator: (none)
• Enrollment: 672
• Arms: 3
• Duration (Months): 22

Study Details

Study Description

Brief Summary

This study is a placebo-controlled study with 8-weeks of double-blind treatment of mometasone furoate dry powder inhaler (MF DPI) 200 mcg twice daily (BID) using two different inhalers, preceded by the Screening Period and by 2 weeks of open-label treatment with one inhalation of MF DPI 200 mcg twice daily in corticosteroid-dependent asthmatic subjects. The objective of this study is to evaluate the therapeutic equivalency of the 100 mcg and 200 mcg MF DPIs when providing the same total daily dose (400 mcg/day).

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Mometasone furoate dry powder inhaler; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 672 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study of the Therapeutic Equivalency of MF DPI 100 mcg and 200 mcg Inhalers in Corticosteroid-Dependent Subjects With Moderate Asthma
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MF DPI 2 x 100 mcg BID 2 inhalations of mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks	Drug: Mometasone furoate dry powder inhaler; Other Names: Asmanex ; Drug: Placebo
Experimental: MF DPI 1 x 200 mcg BID 1 inhalation of mometasone furoate dry powder inhaler (MF DPI) 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily (BID) for 8 weeks	Drug: Mometasone furoate dry powder inhaler; Other Names: Asmanex ; Drug: Placebo
Placebo Comparator: Placebo 2 inhalations of placebo matching mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. [Baseline and Week 8 End]

   Week 8 End = The last 7 days of data with the last day within the range of Days 51 to 64.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

18 years of age, either sex, any race, with a diagnosis of asthma of at least 12 months' duration.

• Must be on a stable regimen of a medium daily dose of ICS for at least 4 weeks immediately prior to Screening. Medium daily doses of ICS are:

• 500 to 1000 mcg beclomethasone CFC

• 250 to 500 mcg beclomethasone HFA

• 600 to 1000 mcg budesonide DPI

• 1000 to 2000 mcg flunisolide

• 250 to 500 mcg fluticasone

• 400 mcg MF

• 1000 to 2000 mcg triamcinolone acetonide.

• Must have a documented reversibility test obtained within 12 months prior to signing the informed consent form. Otherwise, to document a diagnosis of asthma and ensure the subject's responsiveness to bronchodilators, one of the following methods can be used at the Screening Visit, or thereafter, but prior to the Baseline Visit:

• An increase in absolute FEV1 of >=12% and >=200 mL within 30 minutes of administration of 4 puffs of albuterol.

• A PEF variability of >20%, expressed as a percent of the best and lowest morning pre-bronchodilator PEF over at least 1 week.

• A diurnal variation in PEF of >20% based on the difference between the pre-bronchodilator AM value and the post-bronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value any day during the Run-in Period.

• At Screening and Baseline, the subject's FEV1 must be >=60% predicted, when all restricted medications have been withheld for the appropriate intervals. If, based on the clinical judgment of the investigator, there is no harm in changing the subject's asthma therapy, subjects on LABAs must be willing to discontinue the LABA and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 weeks prior to randomization.

• Clinical laboratory tests conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the subject is instructed to start using open-label MF DPI run-in medication. A chest x-ray performed at the Screening Visit or any type of chest imaging within 12 months prior to the Screening Visit must be clinically acceptable to the investigator.

• A female of childbearing potential must be using a medically acceptable, adequate form of birth control. This includes: 1) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant); 2) medically prescribed IUD; 3) condom in combination with a spermicide (double-barrier method); 4) monogamous relationship with a male partner who has had a vasectomy. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A subject of childbearing potential who is not currently sexually active must agree and consent to using a medically acceptable method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A subject of childbearing potential must have a negative serum pregnancy test at Screening.

Exclusion Criteria:

• A change in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit.

• A clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization, or treatment with additional, excluded asthma medication at any time from the Screening Visit up to and including the Baseline Visit).

• Treatment in the emergency department or admission to the hospital for an asthma exacerbation 12 months prior to Screening.

• An upper or lower respiratory tract infection within the 4 weeks of to Screening. Visits can be rescheduled to meet this requirement.

• Evidence of clinically significant oropharyngeal candidiasis at Baseline with or without treatment. If there is evidence of oropharyngeal candidiasis at Screening and/or during the MF DPI Run-in Period, the subject may be treated as appropriate and the Baseline Visit can be scheduled upon resolution. If there is evidence of oropharyngeal candidiasis at the Baseline Visit, the subject may be treated as appropriate and the visit can be rescheduled upon resolution.

• A smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history >10 pack-years.

• Requires more than twelve inhalations of albuterol or more than 2 treatments with nebulized beta-agonists on any 2 consecutive days during the Run-in Period.

• Ever required mechanical ventilation secondary to an asthma exacerbation.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00521599
• Other Study ID Numbers: P04828
• First Posted: Aug 28, 2007
• Last Update Posted: Feb 22, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Asthma; Mometasone Furoate

Study Results

Participant Flow

Arm/Group Title	MF DPI 2 x 100 mcg BID	MF DPI 1 x 200 mcg BID	Placebo BID
Arm/Group Description	2 inhalations of mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks	1 inhalation of MF DPI 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily for 8 weeks	2 inhalations of placebo matching MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks
Period Title: Overall Study
STARTED	268	268	136
COMPLETED	243	239	100
NOT COMPLETED	25	29	36

Baseline Characteristics

Arm/Group Title	MF DPI 2 x 100 mcg BID	MF DPI 1 x 200 mcg BID	Placebo BID	Total
Arm/Group Description	2 inhalations of mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks	1 inhalation of MF DPI 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily for 8 weeks	2 inhalations of placebo matching MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks	Total of all reporting groups
Overall Participants	268	268	136	672
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	259 96.6%	255 95.1%	131 96.3%	645 96%
>=65 years	9 3.4%	13 4.9%	5 3.7%	27 4%
Sex: Female, Male (Count of Participants)
Female	182 67.9%	178 66.4%	104 76.5%	464 69%
Male	86 32.1%	90 33.6%	32 23.5%	208 31%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8.
Description	Week 8 End = The last 7 days of data with the last day within the range of Days 51 to 64.
Time Frame	Baseline and Week 8 End

Outcome Measure Data

Analysis Population Description

All treated subjects included all but one placebo-treated subject from the All Randomized Subjects data set, who was randomized, but never treated in either the open-label or double-blind Treatment Periods due to non-compliance with the protocol

Arm/Group Title	MF DPI 2 x 100 mcg BID	MF DPI 1 x 200 mcg BID	Placebo BID
Arm/Group Description	2 inhalations of mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks	1 inhalation of MF DPI 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily for 8 weeks	2 inhalations of placebo matching MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks
Measure Participants	268	268	136
Baseline	361.8 (96.7)	374.3 (96.7)	348.4 (96.7)
Week 8 End	6.03 (37.0)	7.65 (37.0)	-7.93 (37.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MF DPI 2 x 100 mcg BID, MF DPI 1 x 200 mcg BID
	Comments	Week 8 End scores
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	assume n=240 per group and standard deviation (STD) = 45 L/min for AM Peak Flow Rate at Week 8. If the two actives are the same, 95% CI of their mean difference has 90% probability to be completely within +/- 15 L/min.
Statistical Test of Hypothesis	p-Value	0.654
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.62
	Confidence Interval	(2-Sided) 95%; -8.74 to 5.49
	Parameter Dispersion	Type: Standard Deviation; Value: 37.0
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MF DPI 2 x 100 mcg BID, Placebo BID
	Comments	Week 8 End scores
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MF DPI 1 x 200 mcg BID, Placebo BID
	Comments	Week 8 End scores
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANOVA
	Comments

Adverse Events

Arm/Group Title	OL 1 X 200 mcg BID		MF DPI 2 x 100 mcg BID		MF DPI 1 x 200 Mcg BID		Placebo
Arm/Group Description	Open-label MF DPI 200 mcg BID		2 inhalations of MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks		1 inhalation of mometasone furoate dry powder inhaler (MF DPI) 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily (BID) for 8 weeks		2 inhalations of placebo matching MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks
All Cause Mortality
	OL 1 X 200 mcg BID		MF DPI 2 x 100 mcg BID		MF DPI 1 x 200 Mcg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	OL 1 X 200 mcg BID		MF DPI 2 x 100 mcg BID		MF DPI 1 x 200 Mcg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/950 (0.1%)		3/268 (1.1%)		2/268 (0.7%)		2/135 (1.5%)
Gastrointestinal disorders
OESOPHAGEAL RUPTURE	0/950 (0%)	0	1/268 (0.4%)	1	0/268 (0%)	0	0/135 (0%)	0
SMALL INTESTINAL OBSTRUCTION	0/950 (0%)	0	0/268 (0%)	0	1/268 (0.4%)	1	0/135 (0%)	0
General disorders
CHEST PAIN	1/950 (0.1%)	1	0/268 (0%)	0	0/268 (0%)	0	0/135 (0%)	0
Infections and infestations
DIVERTICULITIS	0/950 (0%)	0	1/268 (0.4%)	1	0/268 (0%)	0	0/135 (0%)	0
POST PROCEDURAL INFECTION	0/950 (0%)	0	0/268 (0%)	0	1/268 (0.4%)	1	0/135 (0%)	0
Injury, poisoning and procedural complications
JOINT DISLOCATION	0/950 (0%)	0	0/268 (0%)	0	0/268 (0%)	0	1/135 (0.7%)	1
LOWER LIMB FRACTURE	0/950 (0%)	0	0/268 (0%)	0	0/268 (0%)	0	1/135 (0.7%)	1
MULTIPLE INJURIES	0/950 (0%)	0	0/268 (0%)	0	0/268 (0%)	0	1/135 (0.7%)	1
OPEN FRACTURE	0/950 (0%)	0	0/268 (0%)	0	0/268 (0%)	0	1/135 (0.7%)	1
Renal and urinary disorders
NEPHROLITHIASIS	0/950 (0%)	0	1/268 (0.4%)	1	0/268 (0%)	0	0/135 (0%)	0
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/950 (0.1%)	1	0/268 (0%)	0	0/268 (0%)	0	1/135 (0.7%)	1
Other (Not Including Serious) Adverse Events
	OL 1 X 200 mcg BID		MF DPI 2 x 100 mcg BID		MF DPI 1 x 200 Mcg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/950 (1.1%)		19/268 (7.1%)		30/268 (11.2%)		16/135 (11.9%)
Infections and infestations
NASOPHARYNGITIS	6/950 (0.6%)	6	10/268 (3.7%)	10	16/268 (6%)	16	6/135 (4.4%)	8
UPPER RESPIRATORY TRACT INFECTION	4/950 (0.4%)	4	10/268 (3.7%)	11	14/268 (5.2%)	14	10/135 (7.4%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of sponsor. The investigator further agrees to provide the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication. The sponsor has the right to review and comment. If the parties disagree, the investigator agrees to meet with the sponsor's representative in order to resolve such issues.