AsthmaNCT00643578

Dose-response of Inhaled Formoterol Using Methacholine Challenge as a Bioassay

A study testing formoterol and Dry Powder Inhaler (Twisthaler) in people with Asthma, run by University of Florida at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Asthma
What is being tested?: formoterol and Dry Powder Inhaler (Twisthaler)
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: Mar 2008to Jan 2009
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Non-smoking male or female 18 60 years of age, with a previous diagnosis of asthma that has been stable for at least 4 weeks and which is unlikely to exacerbate during the study because of, for example, seasonal allergen exposure. Women of childbearing age must not be pregnant or nursing, and must be using an acceptable method of contraception.
Ability to perform ATS/ERS-acceptable and reproducible spirometry7
Screening FEV1 ≥70% of predicted for height, age, sex, and race when short-acting inhaled bronchodilators are withheld for at least 6 hours
At least a 20% decrease in FEV1 after inhaling ≤4 mg/mL of methacholine (i.e., a PC20 FEV1 ≤4 mg/mL)
Can be taught to use the dry powder device in accordance with the product's medication guide.
If using an oral inhaled or intranasal corticosteroid, dosage must be stable for at least 4 weeks.

Who cannot join

Allergy or sensitivity to inhaled methacholine, formoterol or to other β2 agonists
Intolerance to other components of the inhaler or sensitivity to milk proteins
Cigarette smoking in past year or >10 pack-year smoking history
Respiratory tract infection within the last four weeks
History of severe asthma attack requiring hospitalization in the previous 12 months
Short course of oral and/or systemic corticosteroids in the past 4 weeks

Show all 12Show fewer

Inability to withhold caffeinated beverages for 12 hours or medications for appropriate intervals prior to each methacholine challenge
Require treatment with beta-blockers (administered by any route), MAO inhibitors, tricyclic antidepressants, and/or maintenance therapy with systemic corticosteroids
History and/or presence of pulmonary conditions (including but not limited to cystic fibrosis and bronchiectasis) other than asthma
History of clinically-significant cardiovascular, renal, neurologic, liver or endocrine dysfunction. Patients with well-controlled hypertension, hypercholesterolemia or diabetes will not be excluded.
If female, a positive urine β-HCG test
Known or suspected substance abuse (e.g., alcohol, marijuana, etc.) and/or any other medical or psychological conditions that in the investigator's opinion should preclude study enrollment.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Florida Asthma Research Lab
Gainesville, Florida, 32610-0486

Other trials in United States

About this study

Official title: A Pilot Study to Evaluate the Dose-response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma

The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.

Read the detailed description

During the screening visit, subjects'vital signs (heart rate, blood pressure and temperature) will be measured and they will perform standard spirometry. If the results of this test are 70% of normal or greater, they will be examined by a physician, and blood (1 teaspoonful) and urine will be collected for routine laboratory tests (CBC and routine urinalysis). If they are a female, a pregnancy test will be performed.

During the second visit, subjects will inhale 1 or 2 doses of formoterol, (Foradil Aerolizer 12 mcg/capsule) a long-acting bronchodilator and 1 hour later, perform a methacholine test.

At the end of the methacholine test, they will be given albuterol to reverse the effects of methacholine. On the third study day, they will repeat the second visit but with the opposite dose of Foradil.

Conditions: Asthma
Being tested: formoterol, Dry Powder Inhaler (Twisthaler)
Keywords: formoterol, methacholine challenge
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

formoterolDrug
a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
formoterolDrug
a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
Dry Powder Inhaler (Twisthaler)Device
subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose

Study groups in NCT00643578
Study group	Role	What they receive
2	Active comparator	a single dose of 24 mcg of formoterol Receives: Drug: formoterol; Device: Dry Powder Inhaler (Twisthaler)
1	Active comparator	a single dose of 12 mcg of formoterol Receives: Drug: formoterol; Device: Dry Powder Inhaler (Twisthaler)

What is being measured

The primary outcome is the main question the study is designed to answer.

Post-dose PC20
The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second.
Measured: 3-7 days after visits 1 and 2

Secondary outcomes (1)

FEV1
The forced expiratory volume in the first second, expressed as a percent predicted.
Measured: 1 hour after dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2008Jan 2009

First posted26 Mar 2008 (estimated)
Study startMar 2008
Primary completionJan 2009
Study completionJan 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (9)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by University of FloridaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00643578
Sponsor's protocol ID: Ivax-65307
Status last verified: Nov 2011
First submitted: 20 Mar 2008
Last updated: 5 Dec 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Ahrens RC, Harris JB, Milavetz G, Annis L, Ries R. Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma. J Allergy Clin Immunol. 1987 Jun;79(6):876-82. doi: 10.1016/0091-6749(87)90235-1.
PubMed 3294976
Blake KV, Hoppe M, Harman E, Hendeles L. Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation. Chest. 1992 Feb;101(2):309-15. doi: 10.1378/chest.101.2.309.
PubMed 1310456
Hendeles L, Beaty R, Ahrens R, Stevens G, Harman EM. Response to inhaled albuterol during nocturnal asthma. J Allergy Clin Immunol. 2004 Jun;113(6):1058-62. doi: 10.1016/j.jaci.2004.03.046.
PubMed 15208585
Parameswaran KN, Inman MD, Ekholm BP, Morris MM, Summers E, O'Byrne PM, Hargreave FE. Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist. Am J Respir Crit Care Med. 1999 Jul;160(1):354-7. doi: 10.1164/ajrccm.160.1.9812035.
PubMed 10390425
Ahrens RC, Hendeles L, Clarke WR, Dockhorn RJ, Hill MR, Vaughan LM, Lux C, Han SH. Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine. Am J Respir Crit Care Med. 1999 Oct;160(4):1238-43. doi: 10.1164/ajrccm.160.4.9806101.
PubMed 10508813
Creticos PS, Adams WP, Petty BG, Lewis LD, Singh GJ, Khattignavong AP, Molzon JA, Martinez MN, Lietman PS, Williams RL. A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers. J Allergy Clin Immunol. 2002 Nov;110(5):713-20. doi: 10.1067/mai.2002.129036.
PubMed 12417879
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
PubMed 16055882
Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108.
PubMed 9872837
Asmus MJ, Vaughan LM, Hill MR, Chesrown SE, Hendeles L. Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation. Chest. 2002 May;121(5):1634-7. doi: 10.1378/chest.121.5.1634.
PubMed 12006455

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study to Evaluate the Dose-response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma
ClinicalTrials.gov ID: NCT00643578
Acronym / sponsor ID: Ivax-65307
Conditions: Asthma
Keywords: formoterol, methacholine challenge
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: University of FloridaUniversity, hospital or other
Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.
Study start: Mar 2008
Primary completion: Jan 2009 (actual)
Study completion: Jan 2009 (actual)
First posted: 26 Mar 2008 (estimated)
Results: Posted 18 Nov 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.

Detailed description

During the second visit, subjects will inhale 1 or 2 doses of formoterol, (Foradil Aerolizer 12 mcg/capsule) a long-acting bronchodilator and 1 hour later, perform a methacholine test.

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
2	Active comparator	Drug: formoterol, Device: Dry Powder Inhaler (Twisthaler)a single dose of 24 mcg of formoterol
1	Active comparator	Drug: formoterol, Device: Dry Powder Inhaler (Twisthaler)a single dose of 12 mcg of formoterol

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Non-smoking male or female 18 60 years of age, with a previous diagnosis of asthma that has been stable for at least 4 weeks and which is unlikely to exacerbate during the study because of, for example, seasonal allergen exposure. Women of childbearing age must not be pregnant or nursing, and must be using an acceptable method of contraception.
Ability to perform ATS/ERS-acceptable and reproducible spirometry7
Screening FEV1 ≥70% of predicted for height, age, sex, and race when short-acting inhaled bronchodilators are withheld for at least 6 hours
At least a 20% decrease in FEV1 after inhaling ≤4 mg/mL of methacholine (i.e., a PC20 FEV1 ≤4 mg/mL)
Can be taught to use the dry powder device in accordance with the product's medication guide.

Key exclusion criteria (12 listed)

Allergy or sensitivity to inhaled methacholine, formoterol or to other β2 agonists
Intolerance to other components of the inhaler or sensitivity to milk proteins
Cigarette smoking in past year or >10 pack-year smoking history
Respiratory tract infection within the last four weeks
History of severe asthma attack requiring hospitalization in the previous 12 months

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
formoterola single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)	Drug	2
formoterola single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)	Drug	1
Dry Powder Inhaler (Twisthaler)subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose	Device	1, 2

Primary outcome

Post-dose PC20
Time frame: 3-7 days after visits 1 and 2
The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second.

1 secondary outcome

FEV1
Time frame: 1 hour after dose

Results and safety

Results posted to the registry on 18 Nov 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Formoterol 12 First	6	4
Formoterol 24 First	6	6

Primary outcome: Post-dose PC20

Time frame: 3-7 days after visits 1 and 2. Geometric mean (95% Confidence Interval). Unit: mg/mL

Measure	12 Mcg Formoterol n = 10	24 Mcg Formoterol n = 10
Value	7 (2 to 22)	16 (5 to 45)

Population analysed: Of the 12 subjects who qualified for randomization, 2 had a PC20 greater than 128 mg/mL (the maximum concentration of methacholine administered), after receiving 12 mcg of formoterol. Therefore, they were discontinued from the study since their PC20 would not be measurable with a higher dose of formoterol.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Formoterol 12	0 of 10 (0%)	0 of 10 (0%)	Not reported
Formoterol 24	0 of 10 (0%)	0 of 10 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 3294976Ahrens RC, Harris JB, Milavetz G, Annis L, Ries R. Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma. J Allergy Clin Immunol. 1987 Jun;79(6):876-82. doi: 10.1016/0091-6749(87)90235-1.
Background: PubMed 1310456Blake KV, Hoppe M, Harman E, Hendeles L. Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation. Chest. 1992 Feb;101(2):309-15. doi: 10.1378/chest.101.2.309.
Background: PubMed 15208585Hendeles L, Beaty R, Ahrens R, Stevens G, Harman EM. Response to inhaled albuterol during nocturnal asthma. J Allergy Clin Immunol. 2004 Jun;113(6):1058-62. doi: 10.1016/j.jaci.2004.03.046.
Background: PubMed 10390425Parameswaran KN, Inman MD, Ekholm BP, Morris MM, Summers E, O'Byrne PM, Hargreave FE. Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist. Am J Respir Crit Care Med. 1999 Jul;160(1):354-7. doi: 10.1164/ajrccm.160.1.9812035.
Background: PubMed 10508813Ahrens RC, Hendeles L, Clarke WR, Dockhorn RJ, Hill MR, Vaughan LM, Lux C, Han SH. Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine. Am J Respir Crit Care Med. 1999 Oct;160(4):1238-43. doi: 10.1164/ajrccm.160.4.9806101.
Background: PubMed 12417879Creticos PS, Adams WP, Petty BG, Lewis LD, Singh GJ, Khattignavong AP, Molzon JA, Martinez MN, Lietman PS, Williams RL. A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers. J Allergy Clin Immunol. 2002 Nov;110(5):713-20. doi: 10.1067/mai.2002.129036.
Background: PubMed 16055882Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
Background: PubMed 9872837Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108.
Background: PubMed 12006455Asmus MJ, Vaughan LM, Hill MR, Chesrown SE, Hendeles L. Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation. Chest. 2002 May;121(5):1634-7. doi: 10.1378/chest.121.5.1634.

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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Leslie Hendeles, PharmD principal investigator

University of Florida

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing formoterol and Dry Powder Inhaler (Twisthaler) in people with Asthma, run by University of Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post-dose PC20 (time frame: 3-7 days after visits 1 and 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00643578, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2011.