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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Efficacy, Safety, Tolerability, and Pharmacokinetics of Trospium Inhalation Powder (TrIP) Administered to Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Placebo
* Drug: TrIP-2D
* Drug: TrIP-2SS
* Drug: TrIP-2D
* Drug: TrIP-2SS + Foradil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Represents Dose A in the Dosing Sequence assignments. | Drug: Placebo<br>* Supplied as an empty size-2 capsule and administered as a single dose via C2S inhaler.<br>|
| Experimental: TrIP-2D (100mcg)<br>Represents Dose B | Drug: TrIP-2D<br>* 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.<br>|
| Experimental: TrIP-2SS (100mcg)<br>Represents Dose C | Drug: TrIP-2SS<br>* 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.<br>|
| Experimental: TrIP-2D (400mcg)<br>Represents Dose D | Drug: TrIP-2D<br>* 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.<br>|
| Experimental: TrIP-2SS (100mcg) + Foradil (12mcg)<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, pulmonary, inhalation