TBS02: Terbutaline Sulfate in Adults With Asthma
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Detailed Description
Primary Objectives:
-
Describe differences in the PK profiles of terbutaline sulfate administered via the SQ route versus the IV route.
-
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- PK: Maximum concentration (CMAX) [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) [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) [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) [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) [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) [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) [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) [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 Outcome Measures
- Number of Adverse Events (AEs) [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) [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) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant has provided informed consent
-
History of physician-diagnosed asthma
-
Age ≥18 to <50 at time of consent
-
Past evidence of airway reactivity (within 12 months of consent), defined as:
-
Documentation of ≥12% FEV1 improvement following bronchodilator OR
-
Positive methacholine challenge (20% or more FEV1 decrease at ≤ 16 mg/mL)
- Evidence of recent asthma symptoms measured at Screening, 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
-
Willing and able to undergo study procedures and attend required study visits
-
Adequate venous access for blood draws and drug administration, as determined by study investigator, or designee
-
Weight ≥ 40kg
-
FEV1 ≥ 60% predicted on day of terbutaline sulfate dosing
-
Systolic blood pressure (BP) ≤ 150 millimeters of Mercury (mmHg) and diastolic BP ≤ 90 mmHg measured after 10 to 15 minutes of rest
-
Heart rate > 45 and < 110 beats per minute (bpm) measured after 10 to 15 minutes of rest
-
Female participants of child-bearing potential: negative pregnancy test ((uUrine hCG)) at Screening screening 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:
-
Self-reported pregnancy or lactating or breastfeeding
-
Previous enrollment in the current study (any part)
-
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
-
Body Mass Index (BMI) > 35 kg/m2 (class II or III obesity)
-
Moderate to severe renal impairment, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2
-
Self-reported smoking (including any vaping/e-cigarettes/marijuana) in past 6 months
-
Greater than 10 pack-year smoking history
-
Any history of cardiac disease (e.g. coronary insufficiency, cardiac arrhythmias), non-skin cancer, clinically diagnosed hypertension, hyperthyroidism, diabetes mellitus or epilepsy
-
History of ocular, brain, abdominal or thoracic surgery in the 12 months prior to screening
-
Known hypersensitivity to terbutaline sulfate
-
Use of any medications from the following classes within 30 days prior to Visit 1: monoamine oxidase inhibitors, tricyclic antidepressants, betablockers, antihypertensive diuretics
-
Self-reported respiratory tract infection in the 14 days prior to Visit 1
-
Any current chronic condition or past history of disease that, in the opinion of the PI would make the participant unsuitable for the study
-
Baseline prolongation of QTc (QTc ≥ 460 ms by Fridericia's formula)
-
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Kanecia Obie Zimmerman
- Duke Health
- The Emmes Company, LLC
Investigators
- Principal Investigator: Jason Lang, MD, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00107910