Anti-Inflammatory Lipid Mediators in Asthma

NCT03680976 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: PRO16020149
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate the efficacy and safety of 10-nitro-9(E)-octadec-9-enoic acid (CXA-10) in obese adult asthmatics. The study's hypothesis is that 150 mg/day of CXA-10 for 12 weeks will alleviate obesity-related airway hyper-reactivity in obese adult asthmatics.

Conditions

Asthma

Keywords

Asthma; Obesity; Nitrated fatty acids

Outcome Measures

Primary Outcomes (1)

• Change in airway responsiveness after treatment with CXA-10 using a methacholine challenge test

  Measured by the response to administration of methacholine. The PC20 is a calculated value of the amount of methacholine required to cause a 20% fall in the subject's FEV1.

  12 weeks

Secondary Outcomes (3)

• Treatment with CXA-10 compared to baseline: Change in the concentration of Nitrite/Nitrate (NO2/NO3). and NO2-Conjugated Linoleic Acid (CLA) in plasma and urine

  12 weeks

• Treatment with CXA-10 compared to baseline: Characterization of the pharmacokinetic (PK) profile of CXA-10 in plasma and urine

  12 weeks

• Treatment with CXA-10 compared to baseline: Changes in airway epithelial gene expression

  12 weeks

Study Arms (2)

10-nitro-octadeca-9-enoic acid (CXA-10)

EXPERIMENTAL

CXA-10 150 mg tablet taken orally once a day for 12 weeks

Drug: CXA-10

Placebo

PLACEBO COMPARATOR

Placebo 150 mg tablet taken orally once a day for 12 weeks

Drug: Placebo

Interventions

CXA-10 DRUG

Liquid-filled capsule containing 150 mg CXA-10 in super refined olive oil.

Also known as: 10-nitro-octadeca-9-enoic acid

10-nitro-octadeca-9-enoic acid (CXA-10)

Placebo DRUG

Liquid-filled capsule containing olive oil manufactured to mimic CXA-10 150 mg capsule

Placebo

Eligibility Criteria

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

You may qualify if:

• Adequate completion of informed consent process with written documentation. Male and female patients, 18 to 65 yrs old female subjects should be either post-menopausal, surgically sterile, or women of child-bearing potential (WOCP) with a negative pregnancy test prior to entering the study and who agree to use an acceptable method of contraception, for the duration of the study.
• Diagnosis of asthma: based on previous physician diagnosis for \> 6 months, and either baseline pre-bronchodilator (BD) FEV1 between 50 and 90% predicted with a 12% or greater bronchodilator response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response (\<12% change), within 2 years of Visit 0. If no historical reversibility or historical PC20, and the participant does not reverse 12% at V0, the participant can return for V0a to meet this eligibility criteria.
• Daily treatment with inhaled corticosteroids and long acting beta agonists (ICS/LABA) combination medication for at least 3 months; on a stable dose for the 4 weeks prior to Visit 0
• Asthma control questionnaire ACQ \> 1.5 \& ≤ 3
• Smoking history \<10 pack years and no smoking in the last year
• Body Mass Index (BMI) ≥ 30 kg/m2
• Hemoglobin A1c (HbA1c) \<8%
• Average systolic blood pressure \<160 or diastolic \< 100 mmHg (average of three measurements))
• Resting HR ≥45 beats per minute (BPM) after 5 minute rest at screening
• QTcF interval (Fredericia's correction factor) must be ≤430 msec at screening and pre-dose for males and ≤450 msec for females.
• For randomization: No exacerbations or treatment failures during the run in. Patients, who exacerbate or experience treatment failure during the run-in, may re-enroll 4 weeks after the exacerbation has resolved (completed course of systemic corticosteroids).

You may not qualify if:

• Respiratory tract infection within the last 4 weeks
• Oral or systemic corticosteroid burst within the last 4 weeks
• Asthma-related hospitalization within the last 2 months
• Three or more asthma exacerbations requiring treatment with systemic corticosteroids in the past year consistent with severe asthma
• Asthma-related ER visit within the previous 4 weeks
• Significant or uncontrolled concomitant medical illness including (but not limited to) heart disease, cancer, or diabetes at the discretion of the investigator
• History of ICU admission/intubation due to asthma in the past year
• Current statins use, patients may stop and re-enroll after 4 weeks of stopping statins
• Positive pregnancy test at screening and at pre-dose
• Women who are breastfeeding
• Women of childbearing potential who are unwilling to use an acceptable method of birth control.
• Intolerance or hypersensitivity to the CXA-10 or it's excipients
• Treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of dosing (this includes investigational formulations of marketed products, inhaled and topical drugs
• Unable or unlikely to complete study assessments or the study intervention (i.e. bronchoscopy) poses undue risk to patient in the opinion of the Investigator;
• Any kind of oral nitrates such as nitroglycerin

Sponsors & Collaborators

• Sally E. Wenzel MD: lead

Study Sites (1)

The University of Pittsburgh Asthma Institute at UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Asthma; Obesity

Interventions

CXA-10

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sally E Wenzel, MD

  The University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: September 21, 2018
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: September 21, 2018

Record last verified: 2018-09

Locations

US (1)