TC-6987 for the Treatment of Mild to Moderate Asthma

A Phase II Multicenter, Randomized, Double-Blind,Parallel Group, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetic Parameters of TC-6987 in Subjects With Persistent Mild to Moderate Asthma

This study is designed to determine whether TC-6987 improves respiratory function in subjects with asthma by reducing airway hyper-responsiveness and inflammation.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: TC-6987; Drug: Placebo

Detailed Description

Asthma is a common, chronic inflammatory disorder of the airways that affects an estimated 20 to 22 million people in the United States. It is characterized by variable and recurring symptoms, notably airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The bronchospasm is caused by inflammation of the muscles surrounding the air passageways, making them smaller, thus more difficult for air to freely move in and out of the lungs. Cardinal symptoms of asthma include coughing, chest tightness, shortness of breath and wheezing. These symptoms are often more severe in the morning and late night, and usually reversible with medications. Clinically, asthma is typically classified according to the frequency of symptoms, forced expiratory volume in 1 second (FEV1), and peak expiratory flow rate.

The rationale for this Phase II proof of concept study is to demonstrate that TC-6987 improves respiratory function in subjects with asthma, compared to placebo, as measured by the Baseline FEV1 on Day 1 compared to the End-of-Treatment FEV1 on Day 28 or Early Withdrawal (EW); and also to assess the safety and tolerability profile of TC-6987 in subjects with asthma.

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Medical Research of Arizona
  • California
    • Los Angeles, California, United States, 90025
      • California Allergy and Asthma Medical Group, Inc.
    • Palmdale, California, United States, 93551
      • California Allergy & Asthma Medical Group
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Waterbury Pulmonary Associates
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Sarasota, Florida, United States, 34233
      • Sarasota Clinical Research
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, Inc.
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Allergy Partners of Western North Carolina
  • Ohio
    • Sylvania, Ohio, United States, 43560
      • Toledo Center for Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy & Asthma Clinical Research Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon, PC
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 19115
      • Altoona Lung Specialists
    • Philadelphia, Pennsylvania, United States, 19115
      • Allergy & Asthma Research of New Jersey, Inc.
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Texas
    • Houston, Texas, United States, 77036
      • Pioneer Research Solutions
    • San Antonio, Texas, United States, 78205
      • Paragon Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Utah Clinical Trials, LLC
  • Virginia
    • Richmond, Virginia, United States, 23229
      • VA Adult & Pediatric Allergy & Asthma PC
  • Washington
    • Tacoma, Washington, United States, 98405
      • Pulmornary Consultants, PLLC
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A clinical diagnosis of persistent mild to moderate asthma requiring at least 3 months of daily treatment with inhaled corticosteroids (ICS).
2. A FEV1 value at Screening that is 60-90% of predicted FEV1.
3. Age 18 to 65, males or females.

Exclusion Criteria:

1. Diagnosis or presence of other pulmonary diseases including chronic obstructive pulmonary disease (COPD) and emphysema.
2. Previous life-threatening asthma, such as asthma requiring intubation or ICU admission for asthma.
3. Prolonged hospitalization for asthma within the past year (emergency room treatments using nebulized beta-agonists is permitted).
4. Not able and willing to stop the use of long-acting beta-agonists (LABAs), cromolyn sodium, methylxanthines, anticholinergic agents, leukotriene inhibitors, or any other non-ICS or non-SABA prescription or over-the-counter anti-asthma medication, including antihistamines, during Screening and during the Study.
5. Use of moderate to strong cytochrome P450 3A4 (CYP3A4) inhibitors.
6. Use of oral steroids within the last 1 month, or use of >/= 3 steroid bursts in the last 12 months.
7. History of upper respiratory tract infection (URI) requiring treatment during the last month prior to Screening.
8. Tobacco use within 3 months prior to Screening, or > 5 pack-year lifetime tobacco use.
9. Use of smoking cessation therapy within 3 months prior to Screening.
10. Uncontrolled Gastroesophageal reflux disease (GERD). Subjects on a stable dose of non-prescription or prescription medications who have been symptom free for 4 wks prior to screening are eligible.
11. History within past 6 months of alcohol abuse or illicit drug abuse.
12. Myocardial infarction within 12 months prior to Screening.
13. Known hypothyroidism, vitamin B12, or folic acid deficiency.
14. Known systemic infection (HBV, HCV, HIV, TB).
15. FSH level of < 35 IU/L and a LH level < 25 IU/L.
16. Urine cotinine level > 50 ng/ml.
17. Body Mass Index (BMI) <15 and >35.
18. Participation in another clinical trial in the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo capsule given once daily on Days 1 to 28
Experimental: TC-6987	Drug: TC-6987; TC-6987 50 mg capsule given once daily on Days 1 to 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FEV1 status on Day 28 compared to baseline as a function of treatment (TC-6987 versus placebo)	Co-primary efficacy endpoints: the change in FEV1 from pre dose on Day 1 to pre dose on Day 28; the change in FEV1 from pre dose on Day 1 to 2 h post dose on Day 28	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Asthma Control Days	Number of Asthma Control Days from 14 days prior to Day 1, compared to the 14 days prior to Day 28, as a function of Treatment	Day 1
Decrease in FEV1 after methacholine dose as a function of treatment	Percentage of patients in which methacholine dose decreases FEV1 by 20% (PC20) at Day 29 compared to Day -1	Day 29
Number of Asthma Control Days	Number of Asthma Control Days from 14 days prior to Day 1, compared to the 14 days prior to Day 28, as a function of Treatment	Day 28

Collaborators and Investigators

• Sponsor: Targacept Inc.
• Investigators: Principal Investigator: John Winder, MD, Toledo Center for Clinical Research

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 11, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 15, 2011

Study Record Updates

• Last Update Posted (Estimate): September 13, 2013
• Last Update Submitted That Met QC Criteria: September 3, 2013
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Asthma; Mild to Moderate Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: TC-6987-23-CRD-001