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

Purpose

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	Intervention	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Placebo Drug: TrIP-2D Drug: TrIP-2SS Drug: TrIP-2SS + Foradil	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

MedlinePlus related topics: COPD Lung Diseases

Drug Information available for: Trospium chloride Formoterol fumarate Trospium Formoterol Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by Alkermes, Inc.:

Primary Outcome Measures:

Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) [ Time Frame: 15 minutes to 24 hours post-treatment ] [ Designated as safety issue: No ]
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:

FEV1 Response to Treatment [ Time Frame: Up to 24 hours post-treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: up to 24 hours post-treatment ] [ Designated as safety issue: No ]
Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma.


Enrollment:	24
Study Start Date:	February 2009
Study Completion Date:	July 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility


Ages Eligible for Study:	40 Years to 80 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801684

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


Responsible Party:	Bernard L. Silverman, MD / VP, Clinical Development, Alkermes, Inc.
ClinicalTrials.gov Identifier:	NCT00801684 History of Changes
Other Study ID Numbers:	ALK27-001
Study First Received:	December 2, 2008
Results First Received:	March 18, 2011
Last Updated:	August 17, 2011
Health Authority:	United States: Food and Drug Administration

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 Trospium chloride Formoterol Fumarate Parasympatholytics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs	Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Urological Agents Bronchodilator Agents Anti-Asthmatic Agents Respiratory System Agents Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents

ClinicalTrials.gov processed this record on September 26, 2016