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

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Placebo; Drug: TrIP-2D; Drug: TrIP-2D; Drug: TrIP-2SS; Drug: TrIP-2SS + Foradil

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / 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.; 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); 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 100 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alkermes, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: December 2, 2008
• First Submitted That Met QC Criteria: December 2, 2008
• First Posted (ESTIMATE): December 3, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 19, 2011
• Last Update Submitted That Met QC Criteria: August 17, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: COPD; inhalation; pulmonary
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Luteolytic Agents; Triptorelin Pamoate; Formoterol Fumarate
• Other Study ID Numbers: ALK27-001