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.

Full Title of Study: “A Prospective, Blinded, Cross-Over Trial of the Exposure-Response Relationship of Terbutaline Sulfate in Adults With Asthma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: December 2025

Detailed 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.

Interventions

  • Drug: Terbutaline
    • management of asthma symptoms

Arms, Groups and Cohorts

  • Experimental: Terbutaline Arm A
    • • Arm A: (n=6) IV bolus (0.25 mg) over 5 minutes SQ administration (0.25 mg) Participants in Part 1 Arms A and B (n=12) will be randomized to one of two treatment arms.No masking will be applied for Part 1 or for the SQ dosing in Part 2. All IV treatments in Part 2 will be masked, with exception to the unmasked study pharmacist, refer to the MOP for details.
  • Experimental: Terbutaline Arm B
    • • Arm B: (n=6) SQ administration (0.25 mg) IV bolus (0.25 mg) over 5 minutes Participants in Part 1 Arms A and B (n=12) will be randomized to one of two treatment arms.No masking will be applied for Part 1 or for the SQ dosing in Part 2. All IV treatments in Part 2 will be masked, with exception to the unmasked study pharmacist, refer to the MOP for details.
  • Experimental: Terbutaline Arm C
    • • Arm C: (n=6) SQ (0.25 mg) IV low dose over 5 minutes IV medium dose over 5 minutes IV high dose over 5 minutes Participants in Part 2 (n=18) will be randomized to one of three treatment arms. To maintain masking the first treatment will be 0.25 mg of study drug SQ, followed by one of three IV dose regimes (low, medium, high) below, which are estimated to be 0.1 mg, 0.5 mg, 1.0 mg, but may be adjusted based on the interim analysis completed in Part 1. No masking will be applied for Part 1 or for the SQ dosing in Part 2. All IV treatments in Part 2 will be masked, with exception to the unmasked study pharmacist, refer to the MOP for details.
  • Experimental: Terbutaline Arm D
    • • Arm D: (n=6)SQ (0.25 mg) IV medium dose over 5 minutes IV high dose over 5 minutes IV low dose over 5 minutes Participants in Part 2 (n=18) will be randomized to one of three treatment arms. To maintain masking the first treatment will be 0.25 mg of study drug SQ, followed by one of three IV dose regimes (low, medium, high) below, which are estimated to be 0.1 mg, 0.5 mg, 1.0 mg, but may be adjusted based on the interim analysis completed in Part 1. No masking will be applied for Part 1 or for the SQ dosing in Part 2. All IV treatments in Part 2 will be masked, with exception to the unmasked study pharmacist, refer to the MOP for details.
  • Experimental: Terbutaline Arm E
    • • Arm E: (n=6) SQ (0.25 mg) IV high dose over 5 minutes IV low dose over 5 minutes IV medium dose over 5 minutes Participants in Part 2 (n=18) will be randomized to one of three treatment arms. To maintain masking the first treatment will be 0.25 mg of study drug SQ, followed by one of three IV dose regimes (low, medium, high) below, which are estimated to be 0.1 mg, 0.5 mg, 1.0 mg, but may be adjusted based on the interim analysis completed in Part 1. No masking will be applied for Part 1 or for the SQ dosing in Part 2. All IV treatments in Part 2 will be masked, with exception to the unmasked study pharmacist, refer to the MOP for details.

Clinical Trial Outcome Measures

Primary Measures

  • PK: Maximum concentration (CMAX)
    • Time Frame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and next calendar day after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route versus the IV route.
  • PK: Time to Research Maximum Concentration (Tmax)
    • Time Frame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route versus the IV route.
  • PK: Clearance (Cl)
    • Time Frame: 5 mins, 15 mins, 30 mins, 45 mins, 1 hr, 2 hrs, 3 hrs, 4 hrs, 6 hrs, after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route
  • PK: Volume of Distribution (Vd)
    • Time Frame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route
  • PK: Half Life (t1/2)
    • Time Frame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route
  • Concentration Achieving Maximum FEV1 Improvement (CeMax)
    • Time Frame: 0-6 hours
    • Estimate a target plasma concentration and IV dose which achieves maximum FEV1 improvement from baseline and FEV1 AUC 0 to 6 hours.
  • Area Under the Concentration Time Curve (AUC)
    • Time Frame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and next calendar day after dose
    • Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route versus the IV route.
  • Forced Expiratory Volume in 1 second (FEV1)
    • Time Frame: 0-6 hours
    • Estimate a target plasma concentration and IV dose which achieves maximum FEV1 improvement from baseline and FEV1 AUC 0 to 6 hours.

Secondary Measures

  • Number of Adverse Events (AEs)
    • Time Frame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
    • Adverse events (AEs) in participants receiving terbutaline sulfate.
  • Number of Serious Adverse Events (SAEs)
    • Time Frame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
    • Serious Adverse Events (SAEs) in participants receiving terbutaline sulfate.
  • Number of Suspected Unexpected Serious Adverse Reactions (SUSARs)
    • Time Frame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
    • Suspected Unexpected Serious Adverse Reactions (SUSARs) in participants receiving terbutaline sulfate.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 50 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Kanecia Obie Zimmerman
  • Collaborator
    • Duke Health
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Kanecia Obie Zimmerman, Associate Professor of Pediatrics – Duke University
  • Overall Official(s)
    • Jason Lang, MD, Principal Investigator, Duke University
  • Overall Contact(s)
    • Talaya McCright-Gill, MA, 321 566 3091, talaya.mccright-gill@duke.edu

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