Terbutaline Sulfate in Adults With Asthma (TBS02)

A Prospective, Blinded, Cross-Over Trial of the Exposure-Response Relationship of Terbutaline Sulfate in Adults With Asthma

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.

Study Overview

• Status: Withdrawn
• Conditions: Asthma
• Intervention / Treatment: Drug: Terbutaline

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant has provided informed consent
2. History of physician-diagnosed asthma
3. Age ≥18 to <60 at time of consent

4. Past (within 12 months of consent) or current (at screening visit)evidence of airway reactivity, defined as:

   • Documentation of ≥10% FEV1 improvement following bronchodilator OR
   • Positive methacholine challenge (20% or more FEV1 decrease at ≤ 16 mg/mL)
5. Willing and able to undergo study procedures and attend required study visits.
6. Adequate venous access for blood draws and drug administration, as determined by study investigator, or designee
7. Weight ≥ 40kg
8. FEV1 ≥ 60% predicted on day of terbutaline sulfate dosing
9. Systolic blood pressure (BP) ≤ 150 millimeters of Mercury (mmHg) and diastolic BP ≤ 90 mmHg measured after 10 to 15 minutes of rest
10. Heart rate > 45 and < 110 beats per minute (bpm) measured after 10 to 15 minutes of rest
11. 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 combustible cigarette smoking of more than 1 pack per day.
7. Greater than 20 pack-year smoking history
8. Any history of cardiac disease (e.g. coronary insufficiency, cardiac arrhythmias), non-skin cancer, hyperthyroidism, diabetes mellitus type 1, uncontrolled diabetes mellitus type II (HbA1C>7.5 documented within past 12 months of screening) uncontrolled epilepsy (2 or more seizures within the past 12 months and not taking anti-seizure medication)
9. History of ocular, brain, abdominal or thoracic surgery in the 12 months prior to screening
10. Known hypersensitivity to terbutaline sulfate or albuterol
11. Use of any medications from the following classes within 28 days prior to Visit 1: monoamine oxidase inhibitors, tricyclic antidepressants, beta blockers, non-potassium-sparing 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Terbutaline; management of asthma symptoms
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.	Drug: Terbutaline; management of asthma symptoms
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.	Drug: Terbutaline; management of asthma symptoms
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.	Drug: Terbutaline; management of asthma symptoms
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.	Drug: Terbutaline; management of asthma symptoms

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Kanecia Obie Zimmerman
• Collaborators: Duke Health; The Emmes Company, LLC
• Investigators: Principal Investigator: Jason Lang, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Terbutaline
• Other Study ID Numbers: Pro00113848; Pro00107910 (Other Identifier: Duke site protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No