Eosinophilic Esophagitis
Conditions
Brief summary
This is a Phase 1, investigator- and participant-blinded, placebo-controlled, randomized, crossover study to compare bioavailability of AQ280 following single oral doses of a capsule formulation versus a tablet for oral suspension formulation in healthy participants.
Interventions
DRUGAQ280 Capsule
AQ280 administered orally in capsule formulation.
DRUGAQ280 Tablet for Oral Suspension
AQ280 administered orally in tablet for oral suspension formulation.
DRUGPlacebo Capsule
Placebo administered orally in capsule formulation.
DRUGPlacebo Tablet for Oral Suspension
Placebo administered orally in tablet for oral suspension formulation.
Sponsors
AQILION AB
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
- 1. Male or female, of any race, between 18 and 65 years of age, inclusive. 1. Females must not be pregnant or lactating. 2. Males and females of childbearing potential must agree to use contraception 2. Body mass index between 18.0 and 29.9 kg/m2, inclusive. 3. In good health, as determined by no clinically significant findings from medical history, 12-lead ECG and vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in, and from the physical examination at check-in, as assessed by the investigator or designee. 4. Able to comprehend and are willing to sign the ICF and abide by the study restrictions.
Exclusion criteria
- An individual who meets any of the following criteria at screening, unless otherwise stated, will be excluded from participation in this study: Medical Conditions 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator or designee. 2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator or designee. 3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair are allowed). 4. Any of the following: 1. QTcF \>450 ms in males or \>470 ms in females, based on the longest value from the triplicate ECG measurements 2. QRS duration \>120 ms, based on the longest value from the triplicate ECG measurements 3. PR interval \>210 ms, based on the longest value from the triplicate ECG measurements 4. findings which would make QTc measurements difficult or QTc data uninterpretable 5. history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, or family history of long QT syndrome). 5. Participants with an increased risk of thromboembolic events (eg, history of recurrent venous thrombosis or Factor V Leiden mutation). 6. Magnesium \< LLN; participants with values that are borderline \< LLN may be included, as determined by the investigator or designee. 7. History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose of IMP. 8. AST and/or ALT values \> 1.2 × ULN. 9. Congenital nonhemolytic hyperbilirubinemia. 10. Hemoglobin value, neutrophil count (absolute), lymphocyte count (absolute), and/or platelet count \< LLN; participants with values that are borderline \< LLN may be included, as determined by the investigator or designee. 11. White blood cell count \> ULN; participants with values that are borderline \> ULN may be included, as determined by the investigator or designee. 12. eGFR \< 90 mL/min/1.73 m2 (calculated using the CKD-EPI equation3). 13. Significant history of herpes infection (ie, severe herpes outbreaks requiring anti-viral treatment). 14. Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included. 15. Current active tuberculosis based on Quantiferon™ tuberculosis Gold test or history of latent infection. Prior and Concomitant Therapy 16. Administration of any vaccine within 30 days prior to dosing. 17. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee. 18. Use or intend to use any prescription medications/products, other than hormone replacement therapy, oral, implantable, transdermal, injectable, intravaginal, or intrauterine contraceptives, within 14 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee. 19. Use or intend to use any slow-release medications/products considered to still be active within 14 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee. 20. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to dosing, considered to potentially impact participant safety or the objectives of the study, as determined by the investigator or designee. Prior and Concurrent Clinical Study Experience 21. Participation in a clinical study involving administration of an IMP (new chemical entity) in the past 90 days or 5 half-lives of that drug (if known) prior to dosing, whichever is longer. 22. Have previously completed or withdrawn from this study or any other study investigating AQ280 and have previously received AQ280. Diet and Lifestyle 23. Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine. 24. Positive urine drug screen at screening. Positive alcohol test result or positive urine drug screen at check-in. 25. History of alcoholism or drug/chemical abuse within 2 years prior to check-in. Other 26. Use of tobacco- or nicotine-containing products within 3 months prior to check-in. 27. Receipt of blood products within 2 months prior to check-in. 28. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening. 29. Poor peripheral venous access. 30. Participants who, in the opinion of the investigator or designee, should not participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of AUC0-Inf for AQ280 Capsule vs Oral Suspension | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Ratio values were derived based on values for AUC0-Inf of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation. |
| Ratio of Cmax for AQ280 Capsule vs Oral Suspension | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Ratio values were derived based on values for Cmax of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation. |
| Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | AUC0-∞ of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | AUC0-tlast of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Maximum Observed Concentration (Cmax) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Cmax of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Time of the Maximum Observed Concentration (Tmax) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Tmax of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Apparent Terminal Elimination Half-life (t1/2) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | T1/2 of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Apparent Total Clearance (CL/F) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | CL/F of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Vz/F of relative bioavailability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Incidence and severity of adverse events to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Number of Participants With Abnormal Electrocardiograms | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | QTcF interval of \>500 msec or change from baseline (Day 1, predose) \>60 msec |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs - Blood Pressure (Systolic in mm Hg) | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Number of participants with clinically significant abnormalities in vital signs - blood pressure (systolic in mm Hg) to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs - Blood Pressure (Diastolic in mm Hg) | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Number of participants with clinically significant abnormalities in vital signs - blood pressure (diastolic in mm Hg) to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs - Pulse Rate (Beats Per Minute) | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Number of participants with clinically significant abnormalities in vital signs - pulse rate (beats per minute) to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs - Oral Body Temperature (°C) | Screening, Day -1, pre dose and up to 48 hours post dose (up to end of study - approximately 7 weeks) | Number of participants with clinically significant abnormalities in vital signs - oral body temperature (°C) to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation |
| Incidence of Abnormal Physical Examinations | From screening up to end of study (approximately 7 weeks) | Incidence of abnormal physical examinations to assess the safety and tolerability of single oral doses of 100 mg AQ280 capsule formulation and 100 mg AQ280 tablet for oral suspension formulation. Any clinically significant findings observed during physical examinations following dose administration were reported as adverse events. |
Countries
United States
Contacts
STUDY_DIRECTORJan Törnell
AQILION AB
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41 years |
| Body Mass Index | 23.25 kg/m2 |
| Body Weight | 66.15 kg |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 163.60 cm STANDARD_DEVIATION 8.228 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 3 | 0 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 0 / 6 |
Outcome results
None listed