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

Phase 2

Completed

• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Drug: Placebo; Drug: TrIP-2D; Drug: TrIP-2SS; Drug: TrIP-2SS + Foradil

• Registration Number: NCT00801684
• Lead Sponsor: Alkermes, Inc.

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).

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 Timeline

• Study First Submitted: 2008-12-02
• Study First Submitted QC: 2008-12-02
• Study First Posted: 2008-12-03
• Study Start: 2009-02
• Primary Completion: 2009-04
• Study Completion: 2009-07
• Results First Submitted: 2011-03-18
• Status Verified: 2011-05
• Results First Submitted QC: 2011-05-09
• Results First Posted: 2011-05-10
• Last Update Submitted: 2011-08-17
• Last Update Posted: 2011-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Represents Dose A in the Dosing Sequence assignments.
TrIP-2D (100mcg)	TrIP-2D	Represents Dose B
TrIP-2SS (100mcg)	TrIP-2SS	Represents Dose C
TrIP-2D (400mcg)	TrIP-2D	Represents Dose D
TrIP-2SS (100mcg) + Foradil (12mcg)	TrIP-2SS + Foradil	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.

Primary Outcome Measures

Name	Time	Method
Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L)	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

Name	Time	Method
FEV1 Response to Treatment	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.
Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP	up to 24 hours post-treatment	Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma.

Trial Locations

Locations (1)

Spartanburg Medical Research; 🇺🇸 Spartanburg, South Carolina, United States