Advair HFA in Healthy and HAPE Predisposed Subjects

NCT06040268 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 23-0463W81WXH2290024
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.

Conditions

Altitude Edema

Keywords

salmeterol; fluticasone; exercise performance; high altitude pulmonary edema; hypoxia

Outcome Measures

Primary Outcomes (1)

• VO2 max

  peak oxygen consumption with exercise

  day 3 of treatment

Secondary Outcomes (6)

• Aa Gradient

  day 3 of treatment

• blood lactate

  day 3 of treatment

• nadir PaO2

  day 3 of treatment

• highest PaO2

  day 3 of treatment

• MPAP

  day 3 of treatment

Other Outcomes (5)

• Cardiac rhythm (symptomatic)

  7 days of treatment and 7 days of washout

• Cardiac rhythm (asymptomatic)

  7 days of treatment and 7 days of washout

• Serum potassium

  Up to 7 days of treatment

Study Arms (2)

Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days

EXPERIMENTAL

Participants will inhale salmeterol 126 ug and fluticasone 270 ug twice daily for up to 7 days

Drug: Advair HFA

Placebo

PLACEBO COMPARATOR

Participants will inhale placebo (same puff number) twice daily for up to 7 days

Drug: Placebo

Interventions

Advair HFA DRUG

6 puffs (total: salmeterol 126 ug and fluticasone 270 ug) twice daily

Also known as: salmeterol and fluticasone in hydrofluoroalkane (HFA) propellant

Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days

Placebo DRUG

HFA134a inhaler

Also known as: HFA134a (hydrofluoroalkane 134a, same propellant as in Advair HFA)

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent signed prior to entry into the study.
• Male or female age 18-50 years of age
• BMI ≥ 20 and \< 35 kg/m2
• Agreement to comply with the study-required interventions and treatment during the full duration of the study.
• In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip.
• Adequate peripheral venous access for IV insertion and blood sample collection (assessments will be made prior to undergoing further assessments).
• HAPE-susceptible individuals (Study 2 only) must have had a medically documented (hospital admission or emergency room visit) HAPE episode characterized by noncardiogenic pulmonary edema and hypoxemia that occurred during high altitude travel in Colorado and must reside below 3,000 feet (unacclimatized individuals; non-Colorado residents).
• HAPE-resistant individuals (Study 2 only) will have had no evidence of HAPE during high altitude travel in Colorado, and must reside below 3,000 feet (unacclimatized; often being travel partners of HAPE-susceptible subjects).
• Healthy controls (Study 1 only) will all be Colorado residents.

You may not qualify if:

• Currently participating in or has been enrolled in another clinical trial within the last 30 days (observational studies are acceptable).
• Donation of any blood or plasma in the last month, or donation of \> 500 milliliters (ml) of blood within the 3 months preceding study drug administration.
• Female subjects of childbearing potential with positive serum pregnancy (beta human chorionic gonadotropin) test, who are breastfeeding, plan to become pregnant during the study, or decline to either be abstinent or use highly effective birth control if they have sexual intercourse with a male partner (ie, oral contraceptives; contraceptive patches, implants, injections, and rings; intrauterine devices - both hormonally-impregnated and untreated devices) throughout the study and for at least 1 month after study completion;
• Known history of impaired liver function
• Clinically significant laboratory abnormalities (one retest is allowed at the discretion of the Investigator and Medical Monitor), defined as:
• Impaired renal function as estimated glomerular filtration rate \< 60 mL/min/1.73 m2) as estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening.(81)
• Serum Potassium \< 3.2 millimolar (mM)
• aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 2x upper reference limit
• international normalized ratio (INR) \> 1.5
• Fasting serum triglycerides \> 500 mg/dL (lipemic serum affects assays)
• TSH \< 0.5 or \> 5 milliunits/Liter (mU/L)
• Hemoglobin \< 12.0 g/dL
• Bilirubin \> 2, unless consistent with Gilbert's disorder (indirect bilirubinemia)
• Platelet count \< 100,000/µL
• Any other abnormality deemed by the Investigator to exceed normal safety limits for this study or exclude subject participation.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Altitude Sickness; Hypoxia

Interventions

Fluticasone-Salmeterol Drug Combination; Salmeterol Xinafoate; Fluticasone; apaflurane; norflurane

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• James P Maloney, MD

  Univ. of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James P Maloney, MD

CONTACT

3037246072; james.maloney@ucdenver.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: September 15, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)