Asthma, Healthy Adults, Healthy Participants, Healthy Volunteer Study
Conditions
Keywords
Human, Randomized, Metabolism, Excretion, Drug-Drug Interaction, Food effect
Brief summary
The purpose of this study is to learn about the safety of a new study medicine called PF-08103402 in healthy adults (do not have disease) and or in adults with mild-to-moderate asthma. This is the first time the study medicine is being given to people. For Parts A, B, C, D and F, the study is seeking participants who: * Are healthy (do not have disease) males or females who can no longer have children, * Are 18 to 65 years old, * Have a body mass index (BMI) of 16 to 32 kilograms per meter squared and a body weight of more than 50 kilograms (110 pounds). Body mass index is a way to measure body fat by using a person's height and weight For Part A (optional group or cohort 3: Japanese participants only): * A body weight of more than 45 kilograms (100 pounds). * Have 4 biological Japanese grandparents who were born in Japan. For Part E only: * Adults with a documented history of asthma (confirmed by a doctor) for at least 12 months before entering the study. * Have a body mass index (BMI) of 16 to 35 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). The study has six parts: Part A, Part B, Part C, Part D, Part E and Part F. The study medicine will be taken as a suspension or tablet by mouth 1 time a day (except in Parts B and E where it will be taken 1 time a day for 14 days) at the study clinic. The study will help understand: * how the body processes the study medicine in healthy participants (Parts A and B), * how much of the study medicine gets into the bloodstream and if food affects the amount of study medicine in the blood in healthy participants (Part C), * how the study medicine is broken down and leaves the body in healthy participants (Optional Part D), * how the study medicine is processed in adults with mild-to-moderate asthma (Optional Part E), * if taking the study medicine together with another medicine affects how each medicine is processed by the body in healthy participants (Optional Part F). Participants will take part in the study for about 10 weeks (Parts A and F), 12 weeks (Part B), 9 weeks (Parts C and D), and 16 weeks (Part E). During this time, they will have 2 study visits at the study clinic and up to 28 overnight stays (Part A), 18 overnight stays (Parts B and E), 10 overnight stays (Part C), 11 overnight stays (Part D), and 16 overnight stays (Part F). The study team will also call participants 1 time over the phone at the end of the study to assess how they are doing. Study measurements will be taken by body examination, monitoring side effects, blood and urine tests, heart tests (ECG), vital signs (blood pressure and pulse), questionnaires (Parts C and E), stool samples (Part D only), and breathing tests (Part E only).
Interventions
DRUGPF-08103402
Oral suspension (Parts A to F); Tablets (Parts C and F only)
DRUGPlacebo
Oral suspension (Parts A, B and E).
DRUGMidazolam
Oral syrup
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Parts A, B, and E (Double-blind) Parts C, D, and F (Open-label)
Intervention model description
Sequential design (Part A), Parallel design (Part B), Crossover design (Parts C & F), Single period (Parts D & E)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion criteria (Parts A, B, C, D and F): 1. Are males or females who can no longer have children, 2. Are 18 to 65 years old, 3. Have a body mass index (BMI) of 16 to 32 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). For Part A (Optional group or cohort 3: Japanese participants only): 1. A total body weight of more than 45 kg (100 pounds). 2. Have 4 biological Japanese grandparents who were born in Japan. For Part E only: 1. Adults with a documented doctor's-diagnosis history of asthma for at least 12 months before entering the study. 2. Have a body mass index (BMI) of 16 to 35 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). Key
Exclusion criteria
1. Evidence or history of clinically significant medical conditions. 2. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb). 3. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. 4. Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. 5. Any history of parasitic infection requiring treatment within 28 days prior to screening. 6. Positive tuberculosis infection test result. 7. Part C only: Evidence or history of conditions interfering with the ability to taste. 8. Part D only: History of irregular bowel movements. 9. Part E only: Evidence of lung disease(s) other than asthma. 10. Part E only: Asthma exacerbation within 3 months prior to screening. 11. Part F only: History of acute narrow-angle glaucoma, untreated open-angle glaucoma, sleep apnea, respiratory insufficiency, myasthenia gravis or adverse reaction to midazolam or other benzodiazepines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | Parts A: Change From Baseline to Day 7; Part B and E: Change From Baseline to Day 17 | Part A: Cohorts 1, 2 and Cohort 3 (optional). Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). Part E: Cohorts 11 (optional) and 12 (optional). |
| Area under the curve from time zero to extrapolated infinite time (AUCinf) if data permit, otherwise (AUClast) in the fasted state | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 | Part C: Cohort 9 |
| Maximum observed plasma concentration (Cmax) in the fasted state | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 | Part C: Cohort 9 |
| Total recovery of drug-related material in urine and feces separately, and both routes combined, expressed as a percent of total dose administered | Pre-dose (Hour 0) and at 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 hours post-dose (Day 2) | Part D: Cohort 10 (optional) |
| Maximum observed plasma concentration (Cmax) | Pre-dose (Hour 0) and at 0.5, 1, 2, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 hours post-dose (Day 2) | Part F: Cohort 13 (optional) |
| Area under the curve from time zero to extrapolated infinite time (AUCinf) if data permit, otherwise AUClast | Pre-dose (Hour 0) and at 0.5, 1, 2, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 hours post-dose (Day 2) | Part F: Cohort 13 (optional) |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Parts A: Change From Baseline to Day 7; Part B and E: Change From Baseline to Day 17 | Part A: Cohorts 1, 2 and Cohort 3 (optional). Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). Part E: Cohorts 11 (optional) and 12 (optional). |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | Parts A: Up to Day 36; Part B and E: Up to Day 50 | Part A: Cohorts 1, 2 and Cohort 3 (optional). Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). Part E: Cohorts 11 (optional) and 12 (optional) |
| Number of Participants with Serious Adverse Events (SAEs) | Parts A: Up to Day 36; Part B and E: Up to Day 50 | Part A: Cohorts 1, 2 and Cohort 3 (optional). Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). Part E: Cohorts 11 (optional) and 12 (optional) |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Parts A: Change From Baseline to Day 7; Part B and E: Change From Baseline to Day 17 | Part A: Cohorts 1, 2 and Cohort 3 (optional). Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). Part E: Cohorts 11 (optional) and 12 (optional) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Half-life (t½) if data permit | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 and 36 hours post-dose (Day 2) | Part A: Cohorts 1, 2 and Cohort 3 (optional) |
| Area under the curve over 1 dosing interval (AUCtau) | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1, Day 7 and Day 14 | Part B: Cohorts 4, 5, 6, and 7 and Cohort 8 (optional). |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | Up to Day 36 | Part C: Cohort 9 |
| Number of Participants With Serious Adverse Events (SAEs) | Up to Day 36 | Part C: Cohort 9 |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Change From Baseline to Day 4 | Part C: Cohort 9 |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Change From Baseline to Day 4 | Part C: Cohort 9 |
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | Change From Baseline to Day 4 | Part C: Cohort 9 |
| Area under the curve from time zero to extrapolated infinite time (AUCinf) if data permit, otherwise AUClast | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1, 24 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6), 144 hours post-dose (Day 7) | Part D: Cohort 10 (optional) |
| Change From Baseline (CFB) in Fractional concentration of exhaled Nitric Oxide (FeNO) at Day 14 | Pre-dose (Hour 0) and at 72 hours post-dose (Day 4), 144 hours post-dose (Day 7), 264 hours post-dose (Day 12), 312 hours post-dose (Day 14) and 384 hours post-dose (Day 17) | Part E: Cohorts 11 (optional) and 12 (optional) |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 51 | Part F: Cohort 13 (optional) |
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 and 36 hours post-dose (Day 2) | Part A: Cohorts 1, 2 and Cohort 3 (optional). |
| Maximum observed plasma concentration (Cmax) | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 and 36 hours post-dose (Day 2) | Part A: Cohorts 1, 2 and Cohort 3 (optional). |
| Time of Maximum observed plasma concentration (Tmax) | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 and 36 hours post-dose (Day 2) | Part A: Cohorts 1, 2 and Cohort 3 (optional). |
| Area under the curve from time zero to extrapolated infinite time (AUCinf) if data permit | Pre-dose (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1 and at 24 and 36 hours post-dose (Day 2) | Part A: Cohorts 1, 2 and Cohort 3 (optional). |
Countries
United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed