Clinical trial NCT04631354: Study in Healthy Adults to Quantify Lung Deposition and Distribution of Radio-labelled S-770108 Inhalation Powder Formulation Delivered by a Novel Inhaler Device
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-17
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The primary objective of this study is to assess the total lung deposition of radiolabelled S-770108 inhalation powder formulation after each of two separate single inhaled doses in healthy adult participants at two different target peak inspiratory flow rates (PIFRs)


Eligibility criteria: Inclusion Criteria:

1. Subjects who are able to understand this study and comply with all study procedures, are able to be trained and use the device correctly at screening and willing to provide written informed consent before screening.
2. Subjects judged to be healthy by the principal or sub investigator, based on medical history and clinical evaluation.
3. Male and female subjects ≥ 40 to ≤ 80 years of age at the time of informed consent.
4. Subjects whose body mass index (BMI) is ≥ 18.0 and \< 30.0 kg/m2 during the screening visit．
5. Subjects able to produce a peak inspiratory flow rate of at least 30.00L/min at screening using the investigational device attached to an electronic flow meter.
6. Subjects who have smoked within 12 months before admission cannot be entered the study.
7. Subjects judged to have normal lung function. Specifically, with percent predicted forced expiratory volume in 1 second (%FEV1) ≥ 80% and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio ≥70%.
8. Male subjects are eligible to participate if they agree to the following during the treatment period and for at least 3 months (a spermatogenesis cycle) after the last dose of study intervention.

   * Refrain from donating sperm.
   * Must agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as described in Appendix 2, as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
9. Female subjects who agree to use of appropriate contraception measures from time of screening until 3 months after the last dose of study drug, except for female subjects who are surgically sterile by bilateral oophorectomy for at least 6 weeks with appropriate documentation or who are post-menopausal (defined as at least 6 months of spontaneous amenorrhea in woman \> 45 years with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL at screening, or at least 12 months of spontaneous amenorrhea in woman \> 45 years)

Exclusion Criteria:

1. Subjects deemed by the principal or sub investigator to be ineligible for the study due to history of, or concurrent and clinically significant metabolic or endocrine, hepatic, renal, haematological, respiratory, cardiovascular, gastrointestinal, urological, immunological, neurological or psychiatric disorders, or any malignant neoplasms at any diagnosed stage.
2. Radiation exposure, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2018, shall participate in the study.
3. Subjects who have a history of clinically relevant respiratory disease, diseases affecting respiratory function, E.N.T. diseases, or lung surgery.
4. Subjects who have had an upper respiratory infection in the last 7 days which could affect inhalation/absorption of study medication.
5. Subjects who use regular medication (prescribed and/or over the counter) or have used any medication (excluding non-prescription drugs, vitamins, and dietary or herbal supplements which do not interfere with respiratory function according to their labelling) within 14 days before admission; exceptions may be permitted on a case by case basis if considered not to interfere with the aims of the study and agreed by the investigator and sponsor's medical monitor.
6. Subjects with a history of lactose intolerance, intolerance to dairy products, or a history of gluten intolerance.
7. Subjects with a history of serious adverse reaction or serious hypersensitivity to the active ingredient or excipients in any drug.
8. Subjects with a history of drug and/or alcohol addiction within the past 2 years before screening or a positive test for drugs or alcohol at screening or admission visit.
9. Regular alcohol consumption in males of \> 21 units per week, or females of \> 14 units per week (1 unit = 1/2 pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
10. Subjects with a positive result on any of the tests for the serologic detection of human immunodeficiency virus (HIV) antigen/antibody, hepatitis B surface antigen (HBsAg), and hepatitis C antibody.
11. Female subjects who are pregnant, breast-feeding, have a positive pregnancy test result during the screening assessment or admissions; or intending to become pregnant during the study period or within 3 months after the last dose of study treatment.
12. Subjects who have donated \> 400 mL of blood within 3 months before screening, \> 200 mL within 4 weeks before screening, or who donated blood between screening and admission.
13. Subjects who have been exposed to an investigational drug within 90 days prior to study drug administration.
14. Subjects who have previously received pirfenidone (Esbriet®, Pirespa®) in any form, or S 770108.
15. Subjects who are study site employees or immediate family members of a study site employee, or sponsor employees.
16. Subjects who are ineligible for the study for any other reason, as judged by the investigator or sub investigator.

Primary outcomes:
measure: Total lung deposition of 99mTc radio-labelled S-770108
timeFrame: Day 1 of each treatment period
Secondary outcomes:
measure: Central lung deposition of 99mTc radio-labelled S-770108
timeFrame: Day 1 of each treatment period
measure: Peripheral lung deposition of 99mTc radio-labelled S-770108
timeFrame: Day 1 of each treatment period
measure: Penetration index of 99mTc radio-labelled S-770108
timeFrame: Day 1 of each treatment period
measure: Extra-pulmonary deposition of 99mTc radio-labelled S-770108
timeFrame: Day 1 of each treatment period
measure: Number of device deficiencies
timeFrame: Day 1 of each treatment period
measure: Number of participants with adverse events
timeFrame: From first dose of study drug to 14 days after last dose.
Other outcomes:
Locations:
city: Merthyr Tydfil
country: United Kingdom
facility: Simbec-Orion
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: