Trial Outcomes & Findings for Assessment of Arformoterol for Chronic Obstructive Pulmonary Disease (COPD) Using Hyperpolarized 3He MRI (NCT NCT00846287)

Results Overview

Subjects had hyperpolarized helium-3 MR scans completed before administration of an intervention and 2 hours after administration. These images were compared as described: The change in the total ventilation volume (Litres) measured in the hyperpolarized helium-3 MR image from pre-nebulizer inhalation to post-nebulizer inhalation.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

16 participants

Primary outcome timeframe

2 hours

Results posted on

2012-11-01

Participant Flow

Patients with moderate to severe COPD were recruited and enrolled from the UMass Lung and Allergy Center from November 2008 to April 2011.

Participant milestones

Participant milestones
Measure	Active Comparator: Saline Subjects (n=10) will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the placebo will be administered and an hour will pass. The placebo consists of a nebulized saline solution (2.1 mL). After administration of the placebo, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.	Active Comparator: Drug Subjects Subjects (n=10) will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the drug aformoterol will be administered and an hour will pass. BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. After administration of the drug, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.
Overall Study STARTED	16	15
Overall Study COMPLETED	6	10
Overall Study NOT COMPLETED	10	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Assessment of Arformoterol for Chronic Obstructive Pulmonary Disease (COPD) Using Hyperpolarized 3He MRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saline n=16 Participants Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the placebo will be administered and an hour will pass. The placebo consists of a nebulized saline solution (2.1 mL). After administration of the placebo, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.	Drug Subjects n=15 Participants Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the drug aformoterol will be administered and an hour will pass. BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. After administration of the drug, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Age Continuous	63 years STANDARD_DEVIATION 7 • n=5 Participants	68 years STANDARD_DEVIATION 11 • n=7 Participants	66 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: Analysis per protocol.

Subjects had hyperpolarized helium-3 MR scans completed before administration of an intervention and 2 hours after administration. These images were compared as described: The change in the total ventilation volume (Litres) measured in the hyperpolarized helium-3 MR image from pre-nebulizer inhalation to post-nebulizer inhalation.

Outcome measures

Outcome measures
Measure	Placebo Subjects n=6 Participants Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the placebo will be administered and an hour will pass. The placebo consists of a nebulized saline solution (2.1 mL). After administration of the placebo, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag	Brovana Subjects n=10 Participants Subjects (n=10) will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the drug aformoterol will be administered and an hour will pass. BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. After administration of the drug, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.
Change in Total Ventilation Volume	0.154317 Litres Standard Deviation 0.512	-0.13687 Litres Standard Deviation 0.306

SECONDARY outcome

Timeframe: 2 hours

Population: As per protocol

Spirometry was taken which measures FEV1 (in Litres), before administration of an intervention and again 2 hours after administration of an intervention. The change in FEV1 (Litres) from pre-nebulizer inhalation to post-nebulizer inhalation was compared.

Outcome measures

Outcome measures
Measure	Placebo Subjects n=6 Participants Subjects will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the placebo will be administered and an hour will pass. The placebo consists of a nebulized saline solution (2.1 mL). After administration of the placebo, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag	Brovana Subjects n=10 Participants Subjects (n=10) will be required to breath in individual 1 liter bags of gas while in an MRI to produce lung images. These bags of gas are each made up of 333mL of hyperpolarized Helium-3 gas and 667mL of Nitrogen. The first three bags will be administered with a break between each of five to ten minutes. Then the drug aformoterol will be administered and an hour will pass. BROVANA (arformoterol tartrate) Inhalation Solution is supplied as 2 mL of arformoterol tartrate solution packaged in 2.1 mL unit-dose, low-density polyethylene (LDPE) unit-dose vials. Each unit-dose vial contains 15 mcg of arformoterol (equivalent to 22 mcg of arformoterol tartrate) in a sterile, isotonic saline solution, pH-adjusted to 5.0 with citric acid and sodium citrate. After administration of the drug, three additional bags of hyperpolarized helium-3 will be administered, again with five to ten minutes between each bag.
Change in FEV1	-0.12 Litres Standard Deviation 0.25	0.16 Litres Standard Deviation 0.26

Adverse Events

Saline

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Drug Subjects

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Mitchell Albert

UMass Medical School

Phone: (807) 684-7270

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60