Terbutaline Sulfate in Adults With Asthma

Overview

The overall aim in Part 1 is to compare the pharmacokinetic (PK)/pharmacodynamics (PD) relationship in intravenous (IV) versus subcutaneous (SQ) terbutaline sulfate to identify the optimal IV dosing range for use in Part 2.

The overall aim in Part 2 is to evaluate the optimal IV dosing of terbutaline sulfate based on PD response and safety data.

Description

Primary Objectives:

1. Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route versus the IV route.
2. Estimate a target plasma concentration and IV dose which achieves maximum FEV1 improvement from baseline and FEV1 AUC.

Secondary Objective: Describe all adverse events (AEs) in participants receiving terbutaline sulfate.

Eligibility

Inclusion Criteria:

1. Participant has provided informed consent
2. History of physician-diagnosed asthma
3. Age ≥18 to <50 at time of consent
4. Past evidence of airway reactivity (within 12 months of consent), defined as:
   • Documentation of ≥10% FEV1 improvement following bronchodilator OR
   • Positive methacholine challenge (20% or more FEV1 decrease at ≤ 16 mg/mL)
5. Evidence of recent asthma symptoms, defined as either:
   • Self-reported use of short-acting beta-agonist (SABA) for asthma symptoms at least twice/week on average over the past month OR
   • Asthma Control Questionnaire, 5-item version (ACQ - 5) ≥ 1.25
6. Willing and able to undergo study procedures and attend required study visits
7. Adequate venous access for blood draws and drug administration, as determined by study investigator, or designee
8. Weight ≥ 40kg
9. FEV1 ≥ 60% predicted on day of terbutaline sulfate dosing
10. Systolic blood pressure (BP) ≤ 150 millimeters of Mercury (mmHg) and diastolic BP ≤ 90 mmHg measured after 10 to 15 minutes of rest
11. Heart rate > 45 and < 110 beats per minute (bpm) measured after 10 to 15 minutes of rest
12. Female participants of child-bearing potential: negative pregnancy test (urine hCG) and agreement to use effective contraception (complete abstinence from vaginal intercourse, combination barrier and spermicide, partner vasectomy, bilateral tubal ligation, intrauterine device (IUD), progestin implants, or hormonal) during study participation

Exclusion Criteria:

1. Self-reported pregnancy or lactating or breastfeeding
2. Previous enrollment in the current study (any part)
3. Any chronic respiratory condition besides asthma (including, but not limited to Chronic Obstructive Pulmonary Disease (COPD), emphysema, or interstitial lung disease) that in the opinion of the Principal Investigator (PI) or clinical site investigator, would make the participant unsuitable for the study
4. Body Mass Index (BMI) > 35 kg/m2 (class II or III obesity)
5. Moderate to severe renal impairment, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2
6. Self-reported smoking (including any vaping/e-cigarettes/marijuana) in past 6 months
7. Greater than 10 pack-year smoking history
8. Any history of cardiac disease (e.g. coronary insufficiency, cardiac arrhythmias), non-skin cancer, clinically diagnosed hypertension, hyperthyroidism, diabetes mellitus or epilepsy
9. History of ocular, brain, abdominal or thoracic surgery in the 12 months prior to screening
10. Known hypersensitivity to terbutaline sulfate
11. Use of any medications from the following classes within 28 days prior to Visit 1: monoamine oxidase inhibitors, tricyclic antidepressants, beta blockers, antihypertensive diuretics, or systemic corticosteroids
12. Self-reported respiratory tract infection in the 14 days prior to Visit 1
13. Any current chronic condition or past history of disease that, in the opinion of the PI would make the participant unsuitable for the study
14. Baseline prolongation of QTc (QTc ≥ 460 ms by Fridericia's formula)
15. Participation in another research study that includes use of any investigational drug treatment within the 30 days prior to Visit 1, or planned participation during the study period.