ALK27-001: A Study of Trospium Inhalation Powder (TrIP)Administered to Subjects With COPD

Study Description

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Brief Summary:

The purpose of this study was to evaluate the efficacy, safety, and tolerability of single doses of trospium inhalation powder (TrIP) administered to subjects with chronic obstructive pulmonary disease (COPD).

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Placebo; Drug: TrIP-2D; Drug: TrIP-2SS; Drug: TrIP-2SS + Foradil	Phase 2

Detailed Description:

This was a single-center, randomized, double-blind, cross-over, placebo-controlled study. Following screening, each eligible subject was randomized to a dosing sequence. Study subjects received a total of 5 single doses, each separated by a 3- to 14-day washout period. Doses A, B, C, and D were administered in a double-blind fashion, in sequences generated by a 4-period Latin square design. The 4 dosing sequences were: ABCD, BDAC, CADB, and DCBA. Dose E was administered in an open-label fashion as the final dose in each dosing sequence for all subjects.

Subjects reported to the clinic the evening prior to each dose. Protocol assessments were carried out until 24 hours postdose. Pulmonary function testing (via spirometry) was captured at specified timepoints at baseline as well as before and after dosing. Other efficacy and safety outcomes were assessed according to protocol. Blood sampling was performed for assessment of trospium concentrations at specified timepoints.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Efficacy, Safety, Tolerability, and Pharmacokinetics of Trospium Inhalation Powder (TrIP) Administered to Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Study Start Date :	February 2009
Actual Primary Completion Date :	April 2009
Actual Study Completion Date :	July 2009

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Placebo; Represents Dose A in the Dosing Sequence assignments.	Drug: Placebo; Supplied as an empty size-2 capsule and administered as a single dose via C2S inhaler.
Experimental: TrIP-2D (100mcg); Represents Dose B	Drug: TrIP-2D; Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
Experimental: TrIP-2SS (100mcg); Represents Dose C	Drug: TrIP-2SS; Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
Experimental: TrIP-2D (400mcg); Represents Dose D	Drug: TrIP-2D; Trospium inhalation powder containing 400 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
Experimental: TrIP-2SS (100mcg) + Foradil (12mcg); Represents Dose E. All subjects received Dose E as their final (5th) dose, after completing their initial 4 single doses according to their sequence assignment.	Drug: TrIP-2SS + Foradil; Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), plus foradil (12 mcg formoterol fumarate) supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.

Outcome Measures

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Primary Outcome Measures :

1. Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) [ Time Frame: 15 minutes to 24 hours post-treatment ]

   Following screening, each subject was randomized to a sequence of 5 dosing periods (Doses A, B, C, D, and E). Each period was separated by a 3- to 14-day washout interval.

   The dosing formulations were as follows:

   Dose A = placebo Dose B = TrIP-2D (100 μg TrCl formulated in leucine and DPPC) Dose C = TrIP-2SS (100 μg TrCl formulated in leucine and sodium saccharin) Dose D = TrIP-2D (400 μg TrCl) Dose E = TrIP-2SS (100 μg TrCl) + Foradil (12 μg formoterol fumarate) FEV1 (L)was measured at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose.

Secondary Outcome Measures :

1. FEV1 Response to Treatment [ Time Frame: Up to 24 hours post-treatment ]
   Response was defined as the number of subjects reporting a post-treatment FEV1 of ≥12% (or 200 mL) above baseline.
2. Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP [ Time Frame: up to 24 hours post-treatment ]
   Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma.

Eligibility Criteria

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Ages Eligible for Study:	40 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female COPD subjects between the ages of 40 and 80 years
• Body mass index between 18 and 35
• Medically healthy (other than COPD)
• FEV1/FVC less than or equal to 0.70
• Current non-smoker or able to abstain from smoking for at least 8 hours postdose
• Within the previous 6 months, demonstrated improvement in FEV1 (greater than or equal to 10%) 1 hour following administration of ipratropium bromide inhalation (4 puffs)
• Females of childbearing potential must agree to use an acceptable method of contraception for the duration of the study

Exclusion Criteria:

• Asthma in the last 10 years
• Allergic rhinitis, atopy, cystic fibrosis, bronchiectasis, or tuberculosis
• Bladder neck obstruction, including urinary retention or known symptomatic prostatic hypertrophy not controlled with medication
• Narrow angle glaucoma
• Tachyarrhythmia
• Alcohol dependence or illicit drug abuse within the past year
• Using long-term oxygen therapy
• Female subjects who are pregnant or breastfeeding
• Participating in another clinical trial

Contacts and Locations

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Locations

United States, South Carolina
Spartanburg Medical Research
Spartanburg, South Carolina, United States, 29303

Sponsors and Collaborators

Alkermes, Inc.

Investigators

Study Director:	Bernard L. Silverman, MD	Alkermes, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Bernard L. Silverman, MD / VP, Clinical Development, Alkermes, Inc.
ClinicalTrials.gov Identifier:	NCT00801684 History of Changes
Other Study ID Numbers:	ALK27-001
First Posted:	December 3, 2008
Results First Posted:	May 10, 2011
Last Update Posted:	August 19, 2011
Last Verified:	May 2011

Keywords provided by Alkermes, Inc.:

COPD; pulmonary; inhalation

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Formoterol Fumarate; Trospium chloride; Triptorelin Pamoate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents	Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents