The Multicenter Topic Trial

NCT04066751 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-300003967P30DK072482
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this protocol is to test the safety, pharmacokinetics, and pharmacodynamics of the Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. This project will investigate the hypothesis that ivacaftor can augment CFTR activity in individuals with COPD who exhibit chronic bronchitis, resulting in meaningful improvements in epithelial function and respiratory health. The study is a multicenter, randomized, double-blind, placebo-controlled, stratified study of orally-administered ivacaftor.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (2)

• CFTR activity

  Change in peripheral CFTR activity as detected by sweat chloride testing

  assessed at day1, day 28, day 56, and day 84

• FEV1

  Change in lung function as measured by FEV1 (Pulmonary Function testing.)

  assesed at day 1, day 28, day 56, and day 84

Study Arms (2)

Ivacaftor

ACTIVE COMPARATOR

Ivacaftor, 150 mg PO every 12 hrs for 84 days

Drug: Ivacaftor

Placebo

PLACEBO COMPARATOR

Placebo, 150 mg PO every 12 hrs for 84 days

Drug: Ivacaftor

Interventions

Ivacaftor DRUG

Ivacaftor will be supplied as a tablet for oral administration, film-coated, 150 mg

Also known as: Kalydeco

Ivacaftor; Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female age 40-80
• A Clinical diagnosis of COPD as defined by GOLD
• At Least a 10 pack year smoking history
• Exhibit symptoms of chronic bronchitis as defined by the Medical Research Council
• FEV1% predicted ≥ 35% and ≤80% Post Bronchodilator
• Clinically stable in the last 4 weeks with no evidence of COPD exacerbation
• Weight of 40 kg-120 kg
• Willingness to use at least one form of acceptable birth control including abstinence, condom with spermicide, or hormonal contraceptives from time of signing ICF through study follow up visit
• Willing to monitor blood glucose if known history of insulin dependent diabetes mellitus
• Capable of giving signed informed consent

You may not qualify if:

• Current Diagnosis of Asthma
• Known Diagnosis of Cystic Fibrosis
• Use of Continuous Oxygen Therapy of greater than 2 liters per minute - patients on 2 liters of Oxygen or less will be excluded if they have been hospitalized for COPD in the prior year or had more than 2 exacerbations requiring steroids and/or antibiotics in the prior year.
• Documented history of drug abuse within the last year
• Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary disease within 28 days before receiving the first dose of study drug.
• Cirrhosis or elevated liver transaminases \> 3X ULN
• GFR \< 50 estimated by Cockroft-Gault
• Any illness or abnormal lab finding that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the subject.
• Pregnant or Breastfeeding
• Subjects taking moderate or strong inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit juice. (Excluded medications and foods including the drugs and foods listed in the IRB HSP application.)
• Uncontrolled Diabetes
• Recent (e.g 1year) arterial thrombotic events (peripheral arterial disease, thrombotic stroke)
• Clinically significant arrhythmias requiring anti-arrhythmic agent(s) or conduction abnormalities that in the opinion of the investigator affect patient safety
• A standard digital ECG demonstrating QTc \>450 msec for men and \> QTc 470 msec for women at screening. If QTc exceeds 450 msec for men and \> QTc 470 msec for women at the screening ECG, the ECG should be repeated 2 more times during the screening period, and the subject will be excluded if the average of the 3 QTc values is \>450 msec for men and \> QTc 470 msec for women.
• Angina symptoms

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Vertex Pharmaceuticals Incorporated: collaborator

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark Dransfield, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 26, 2019
• Study Start: December 1, 2021
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: January 27, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share