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

This study has been completed.
Sponsor:
Information provided by:
Alkermes, Inc.
ClinicalTrials.gov Identifier:
NCT00801684
First received: December 2, 2008
Last updated: August 17, 2011
Last verified: May 2011
  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:


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
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

No publications provided

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:
Respiratory Aspiration
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Formoterol
Trospium chloride
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on September 11, 2014