Selective β2-AR Antagonism in Asthma

Trio Medicines

Status and phase: Completed; Phase 1

Conditions: Asthma

Treatments: Drug: TR4; Other: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07272135

T-030

Details and patient eligibility

About

The objectives are to assess the safety, tolerability and effect on the airways of TR4 in patients with mild-to-moderate asthma. The Phase 1 trial is randomised, double-blind, placebo-controlled, and ascending-dose in design.

Full description

After a run-in period of 2 weeks, 12 eligible patients will be randomised to treatment with either TR4 or placebo. Nine patients will take incremental doses of 2.5, 5, 10 and 20 mg of TR4 capsules, each dose three times daily for 7 days, and then 40 mg three times daily for 21 days, over a total period of 7 weeks. Three patients will take matching placebo capsules in a similar manner.

The number of visits and the types are as follows. There will be a maximum of 10 visits to Hammersmith Medicines Research (HMR) for those subjects who complete the whole study according to the protocol. Visit 1 is an out-patient visit for informed consent and screening. Visit 2 is a short out-patient visit at the start of a 2-week run-in period for those subjects who pass screening. After the run-in period, patients who are still eligible will be given a schedule for 8 further visits (Visits 3-10). Participants will stay on the ward for 2 nights during 5 of those visits (Visits 3-7), and for 1 night during Visit 10. Visits 8 and 9 are short out-patient visits. The study will take each subject ~10 weeks to complete. For purposes of data collection and management the study is divided into one session for screening, a run-in period and 5 treatment periods.

Enrollment: 12 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men or women
• Minimum 21 years old
• History of mild-to-moderate asthma for at least 6 months and controlled by an inhaled SABA, as required
• Otherwise healthy
• Ideally have participated in previous asthma studies
• No corticosteroid for whatever reason within 8 weeks of the start of dosing
• No other prescription medicine within 28 days (apart from a short acting beta-agonist (SABA) or contraceptives in women)
• No over-the-counter medicine within 7 days (apart from acetaminophen) before the start of dosing
• Negative screen for drugs of abuse; forced expiratory volume in 1 second (FEV1) more than or equal to 70% predicted
• Fractional exhaled nitric oxide (FeNO) more than or equal to 35 ppb
• 15% fall in FEV1 after inhaled mannitol (PD15)
• Non-smoker or past smoker (<5 pack years)
• Substitution of subject's SABA inhaler with an anti-cholinergic inhaler, ipratropium bromide, for use as a reliever or rescue medication during a run-in period and during dosing with TR4 or placebo.

Exclusion criteria

• Positive test for hepatitis B & C or HIV
• Drug or alcohol abuse
• Airway infection or asthma exacerbation in the last 4 weeks
• Current seasonal asthma
• History of emergency treatment of asthma
• Loss of more than 400 mL blood, or participation in other clinical trials of unlicensed medicines within the previous 3 months
• Consumption of grapefruit or herbal remedies within the past 7 days
• Objection by the subject's general practitioner (GP)
• Subjects who are sexually active and not using reliable contraception
• Women who are lactating, pregnant or plan to become pregnant during the study period
• Positive polymerase chain reaction (PCR) test for SARS-CoV-2 virus
• Subjects who have not received both doses of a COVID-19 vaccine.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups, including a placebo group

TR4

Experimental group

Description:

After a run-in period of 2 weeks, 9 patients will be randomly assigned to the TR4 treatment arm. These 9 patients will take incremental doses of 2.5, 5, 10, and 20 mg of TR4, each dose three times daily for 7 days, and then 40 mg three times daily for 21 days, over a total period of 7 weeks.

Treatment:

Drug: TR4

Placebo

Placebo Comparator group

Description:

Three patients will take matching placebo capsules in a similar manner to TR4.

Treatment:

Other: Placebo