Terbutaline Sulfate in Adults With Asthma (TBS02)

Kanecia Obie Zimmerman

Status and phase: Suspended; Phase 3; Phase 2

Conditions: Asthma

Treatments: Drug: Terbutaline

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04973345

Pro00113848

Pro00107910

Details and patient eligibility

About

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 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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30 participants in 5 patient groups

Terbutaline Arm A

Experimental group

Description:

• 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.

Treatment:

Drug: Terbutaline

Terbutaline Arm B

Experimental group

Description:

• 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.

Treatment:

Drug: Terbutaline

Terbutaline Arm C

Experimental group

Description:

• 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.

Treatment:

Drug: Terbutaline

Terbutaline Arm D

Experimental group

Description:

• 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.

Treatment:

Drug: Terbutaline

Terbutaline Arm E

Experimental group

Description:

• 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.

Treatment:

Drug: Terbutaline