A scintigraphy study of S-770108/inhaler device in healthy volunteers
Research type
Research Study
Full title
A phase one open label, crossover study in healthy adult subjects to quantify lung deposition and distribution of 99mTc radiolabelled S-770108 inhalation powder formulation delivered by a novel inhaler device
IRAS ID
261987
Contact name
Annelize Koch
Contact email
Sponsor organisation
Shionogi Ltd
Eudract number
2018-004469-15
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 1 months, 27 days
Research summary
Research Summary
This study is a single-dose, crossover, open-label, randomised gamma scintigraphy study investigating the deposition in the lungs and distribution of a dry powder formulation of S-770108 when administered from a novel dry powder inhalation device.S-770108 is a combination of pirfenidone, magnesium stearate and lactose carrier in an inhalable formulation meaning that it can be breathed in rather than swallowed. This drug is being developed for the treatment and management of idiopathic pulmonary fibrosis (IPF) which is a chronic lung disease characterised by progressive decline in lung function and difficulty breathing.
The purpose of this study is to assess the deposition and distribution pattern of S-770108 in the lungs and to additionally determine if changes in inspiratory flow rate affect the inhaler device and its' effectiveness at delivering the drug to its' target.
To facilitate determination of how much of the drug gets into the lungs and the distribution pattern, a technique called gamma scintigraphy will be used. Gamma scintigraphy is a technique for detecting and quantifying a radiolabelled tracer inside the body.
The study will involve the following visits: 1 screening visit, 2 treatment visits (around 3 days in duration, separated by a 5-12 day washout period) and a post-study follow up visit 5-12 days after the last dose.
The study population will be 12 healthy volunteers.
Summary of Results
The purpose of this study was to investigate the distribution of the study drug (S-770108) in the lungs from a dry powder inhaler device following inhalation at 2 different targeted peak inspiratory flow rates.The study drug is being developed for the treatment of Idiopathic Pulmonary Fibrosis (IPF) which is a chronic lung disease that causes scarring of the lungs and leads to progressive difficulty in breathing. S-770108 contains a drug called pirfenidone at a dose of 6 mg per capsule. In this study, participants were administered 2 capsules per treatment period, meaning that the overall dose administered was 24 mg.
The purpose of this study was to further assess the safety of
S-770108 and to formally evaluate how the drug is distributed in the lungs. This will provide key information to support further development of the product. The study drug was administered via a dry powder inhaler device. The purpose of this device is to pierce/break down the capsules to release small particles of the study drug. When inhaled, these small particles can get into the lungs.The study evaluated how much of the drug distributed into the lungs after a single dose from the inhaler at 2 treatment periods where participants were asked to inhale at 2 different target flow rates. Peak inspiratory flow rate is the measure of the maximum amount of air that can be inhaled over the time course of 1 deep breath.
In this study, participants were asked to aim for 2 target peak inspiratory flow rates; one at 15 litres per minute and another at 30 litres per minute. This is important to assess in studies involving inhalers as this flow rate can have an effect on how much of the drug is delivered to the lungs. Therefore, another purpose of this study was to assess if the changes in targeted peak inspiratory flow rate affect how much drug can get into the lungs.
To enable the determination of the distribution of the drug in the lungs, a technique called gamma scintigraphy was used. Gamma scintigraphy is a technique which uses a special camera to detect and measure a radiolabelled tracer inside the body. In this case, the study drug S-770108 contained a small amount of radioactivity within each capsule that allowed the drug to be visible in the lungs when the camera scanned the body.
With respect to the safety objectives of the study, it was determined that the dose of S-770108 was considered to be safe and well tolerated. All adverse events (side effects) reported during the study which were considered to be mild in severity with the majority being considered as related to the study drug i.e., coughing following inhalation etc which resolved immediately following the administration of the study drug.
With respect to the evaluation of the distribution of the drug in the lungs and the measurement of the levels of the study drug in the blood, the following outcomes were reported:
- The distribution of the drug in the lungs was observed to be significantly more at a flow rate of 30 L/min when compared to 15 L/min.
- The inhaler device released significantly more of the study drug at a flow rate of 30 L/min when compared to 15 L/min, showing that the efficiency of the device is dependent on the target flow rate for inhalation.
- The drug was shown to distribute in the appropriate areas of the lungs as desired.
- However, the distribution pattern of the drug between the two different flow rates varied significantly.In summary, the data gathered during the study was considered sufficient to meet the objectives of the study and warrant further clinical trials and investigations of the study drug.
REC name
Wales REC 2
REC reference
19/WA/0152
Date of REC Opinion
21 May 2019
REC opinion
Favourable Opinion