Clinical trial NCT04973345: Terbutaline Sulfate in Adults With Asthma
Official title: A Prospective, Blinded, Cross-Over Trial of the Exposure-Response Relationship of Terbutaline Sulfate in Adults With Asthma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Asthma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Duke Health
name: The Emmes Company, LLC
First posted: 2021-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A Prospective, Blinded, Cross-over Trial of the Exposure-Response Relationship of Terbutaline Sulfate in Adults with Asthma (TBS02)
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: PK: Maximum concentration (CMAX)
timeFrame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and next calendar day after dose
measure: PK: Time to Research Maximum Concentration (Tmax)
timeFrame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
measure: PK: Clearance (Cl)
timeFrame: 5 mins, 15 mins, 30 mins, 45 mins, 1 hr, 2 hrs, 3 hrs, 4 hrs, 6 hrs, after dose
measure: PK: Volume of Distribution (Vd)
timeFrame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
measure: PK: Half Life (t1/2)
timeFrame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours after dose
measure: Concentration Achieving Maximum FEV1 Improvement (CeMax)
timeFrame: 0-6 hours
measure: Area Under the Concentration Time Curve (AUC)
timeFrame: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and next calendar day after dose
measure: Forced Expiratory Volume in 1 second (FEV1)
timeFrame: 0-6 hours
Secondary outcomes:
measure: Number of Adverse Events (AEs)
timeFrame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
measure: Number of Serious Adverse Events (SAEs)
timeFrame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
measure: Number of Suspected Unexpected Serious Adverse Reactions (SUSARs)
timeFrame: From baseline through the end of study (Part I up to 60 days, Part II up to 180 days)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
Study officials:
affiliation: Duke University
name: Jason Lang, MD
role: PRINCIPAL_INVESTIGATOR
References: