Terbutaline Sulfate in Adults With Asthma

Asthma Clinical Trial

— TBS02  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04973345
• Other study ID #: Pro00113848
• Secondary ID: Pro00107910
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 7, 2023
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Duke University
• Contact: Talaya McCright-Gill, MA
• Phone: 321 566 3091
• Email: talaya.mccright-gill[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Terbutaline
management of asthma symptoms

Locations

Country	Name	City	State
United States	Duke Early Phase Research Unit (DEPRU)	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Kanecia Obie Zimmerman	Duke Health, The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)