Eosinophilic Esophagitis (EoE)
Conditions
Brief summary
The principal aim of this study is to obtain safety and tolerability data when AQ280 is administered orally as single and multiple doses to healthy subjects. This information, together with the pharmacokinetic (PK) data, will help establish the doses and dosing regimen suitable for future studies in patients.
Interventions
DRUGAQ280
Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral
DRUGPlacebo
Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral
Sponsors
AQILION AB
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must satisfy all of the following criteria at the screening visit (and/or at check-in, where noted): 1. Males or females, of any race, between 18 and 65 years of age, inclusive. 2. Body mass index between 18.0 and 32.0 kg/m2, inclusive. 3. In good health, determined by no clinically significant findings from medical history, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and check-in and from the physical examination at check-in, as assessed by the investigator (or designee). 4. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception. 5. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by the study restrictions.
Exclusion criteria
Subjects will be excluded from the study if they satisfy any of the following criteria at the screening visit (or at check-in, where noted): 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 any surgical (eg, stomach or intestinal surgery or resection) or medical condition that would potentially alter absorption, distribution, metabolism, and/or excretion of orally administered drugs. Uncomplicated appendectomy and hernia repair will be allowed. Cholecystectomy will not be allowed. 4. History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose of IMP. 5. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values \>1.2 × upper limit of normal (ULN). 6. Congenital nonhemolytic hyperbilirubinemia (including suspicion of Gilbert's syndrome). 7. Hemoglobin value, neutrophil count, and/or lymphocyte count \<lower limit of normal. 8. Clinically significant abnormal ECG at screening or check-in. 9. Positive hepatitis panel and/or positive human immunodeficiency virus test. Subjects whose results are compatible with prior immunization may be included at the discretion of the investigator 10. Current active tuberculosis based on Quantiferon™ tuberculosis Gold test. Prior/concomitant therapy 11. Administration of a coronavirus disease 2019 vaccine in the past 30 days prior to the first dose of investigational medicinal product (IMP). 12. 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 the first dose of IMP, unless deemed acceptable by the investigator (or designee). 13. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to the first dose of IMP, unless deemed acceptable by the investigator (or designee). 14. Use or intend to use slow release medications/products considered to still be active within 14 days prior to check in, unless deemed acceptable by the investigator (or designee). 15. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to check in, unless deemed acceptable by the investigator (or designee). Prior/concurrent clinical study experience 16. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing. 17. Have previously completed or withdrawn from this study. Diet and lifestyle 18. Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits. 19. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in. 20. History of alcoholism or drug/chemical abuse within 2 years prior to check-in. 21. Smoking \>5 cigarettes per day, on average, or use the equivalent tobacco- or nicotine containing products per day. 22. Ingestion of poppy seed , Seville orange , star fruit-, or grapefruit containing foods or beverages within 7 days prior to check-in. Other exclusions 23. Receipt of blood products within 2 months prior to check-in. 24. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening. 25. Poor peripheral venous access. 26. Subjects who, in the opinion of the investigator (or designee), should not participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts | The number of participants who experienced a treatment-emergent event (TEAE) are presented. |
| Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts | The number of total events experienced by participants are presented. |
| Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | Part B (MAD): Screening up to Day 14(±3) | The number of participants who experienced a treatment-emergent event (TEAE) are presented. |
| Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | Part B (MAD): Screening up to Day 14(±3) | The number of total TEAE events experienced by participants are presented. |
| Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | Part A (SAD): Screening up to Day 3 | The number of participants with clinically significant abnormalities in vital signs is presented. Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature |
| Part A (SAD): Number of Participants With Abnormal ECG | Part A (SAD): Screening up to Day 3 | The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec. |
| Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | Part A (SAD): Screening up to Day 3 | The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented. |
| Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | Part B (MAD): Screening up to Day 14(±3) | The number of participants with clinically significant abnormalities in vital signs is presented. Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature |
| Part B (MAD): Number of Participants With Abnormal ECG | Part B (MAD): Screening up to Day 14(±3) | The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec. |
| Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Part B (MAD): Screening up to Day 14(±3) | The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | Days 1, 2 and 3 | Primary PK parameters derived from plasma concentration-time profile of AQ280: area under the concentration time curve from time 0 extrapolated to infinity following Single Oral Dose Administration of 3, 9, 16, 48, and 60 mg AQ280 in a Fasted State and 16 mg AQ280 in a Fed State |
| Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 1 and Day 7 | Maximum observed concentration (Cmax) of metabolite AQ282 following single oral dose administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7). |
| Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Days 1, 2 and 3 | Part A (SAD) - Primary PK parameter derived from plasma concentration-time profile of AQ280: maximum observed concentration (Cmax) following Single Oral Dose Administration of 3, 9, 16, 48, and 60 mg AQ280 in a Fasted State and 16 mg AQ280 in a Fed State |
| Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | Days 1, 2 and 3 | Area under the concentration time curve from time 0 extrapolated to infinity of metabolite AQ282 following single oral dose administration of 3, 9, 16, 48, and 60 mg AQ280 in a fasted state and 16 mg AQ280 in a fed state |
| Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Days 1, 2 and 3 | Maximum observed concentration (Cmax) of metabolite AQ282 following single oral dose administration of 3, 9, 16, 48, and 60 mg AQ280 in a fasted state and 16 mg AQ280 in a fed state |
| Part A (SAD) - Difference in Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity in Fasted State and in Fed State | Days 1, 2 and 3 | Difference in area under the concentration time curve from time 0 extrapolated to infinity derived from plasma concentration-time profile of AQ280 in fasted state and in fed state to assess the effect of food on single oral doses of 16 mg AQ280. The within-subject coefficient of variation is presented under the 16 mg fed results. |
| Part A (SAD) - Difference in Maximum Observed Concentration (Cmax) in Fasted State and in Fed State | Days 1, 2 and 3 | Difference in maximum observed concentration (Cmax) derived from plasma concentration-time profile of AQ280 in fasted state and in fed state to assess the effect of food on single oral doses of 16 mg AQ280. The within-subject coefficient of variation is presented under the 16 mg fed results. |
| Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | Day 1 to Day 7 | Accumulation ratio (AR) AQ280 following multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state on Day 7. ARAUC = accumulation ratio based on area under the concentration-time curve over a dosing interval ARCmax = accumulation ratio based on maximum observed concentration |
| Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 1 and Day 7 | Area under the concentration time curve over a dosing interval (AUCτ) following single oral administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and after multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7). |
| Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 1 and Day 7 | Maximum observed concentration (Cmax) following single oral administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and after multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7). |
| Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 1 and Day 7 | Area under the concentration time curve over a dosing interval (AUCτ) of metabolite AQ282 following single oral dose administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A (SAD): Placebo (Fasted) Single dose of placebo, fasted
Dose form: capsule, hard Method of administration: oral | 8 |
| Part A (SAD): 3 mg (Fasted) Single dose of 3 mg AQ280, fasted
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part A (SAD): 9 mg (Fasted) Single dose of 9 mg AQ280, fasted
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part A (SAD): Placebo (Fasted/Fed) Single dose of placebo fasted on Day 1 of Treatment Period 1 and fed on Day 1 of Treatment Period 2.
Dose form: capsule, hard Method of administration: oral | 2 |
| Part A (SAD): 16 mg (Fasted/Fed) Single dose of 16 mg AQ280 fasted on Day 1 of Treatment Period 1 and fed on Day 1 of Treatment Period 2.
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part A (SAD): 48 mg (Fasted) Single dose of 48 mg AQ280, fasted
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part A (SAD): 60 mg (Fasted) Single dose of 60 mg AQ280, fasted
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part B (MAD): Placebo Placebo, once daily (QD) for seven days
Dose form: capsule, hard Method of administration: oral | 7 |
| Part B (MAD): 9 mg AQ280 9 mg once daily (QD) for seven days
AQ280: Dose form: capsule, hard Method of administration: oral | 7 |
| Part B (MAD): 27 mg AQ280 27 mg once daily (QD) for seven days
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Part B (MAD): 60 mg AQ280 60 mg once daily (QD) for seven days
AQ280: Dose form: capsule, hard Method of administration: oral | 6 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Fasted) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Treatment Period 1 (Fasted) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 2 (Fed Groups Only) | Discontinued prior to dosing in fed period due to a failed drug screen at check-in | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A (SAD): Placebo (Fasted) | Part A (SAD): 3 mg (Fasted) | Part A (SAD): 9 mg (Fasted) | Part A (SAD): Placebo (Fasted/Fed) | Part A (SAD): 16 mg (Fasted/Fed) | Part A (SAD): 48 mg (Fasted) | Part A (SAD): 60 mg (Fasted) | Part B (MAD): Placebo | Part B (MAD): 9 mg | Part B (MAD): 27 mg | Part B (MAD): 60 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 11.65 | 38.8 years STANDARD_DEVIATION 15.46 | 40.0 years STANDARD_DEVIATION 14.7 | 32.0 years STANDARD_DEVIATION 7.07 | 53.5 years STANDARD_DEVIATION 13.63 | 39.8 years STANDARD_DEVIATION 21.78 | 43.0 years STANDARD_DEVIATION 18.21 | 38.0 years STANDARD_DEVIATION 13.96 | 43.6 years STANDARD_DEVIATION 12.75 | 36.3 years STANDARD_DEVIATION 14.64 | 47.8 years STANDARD_DEVIATION 13.67 | 43.0 years STANDARD_DEVIATION 14.97 |
| Body mass index | 26.90 kilograms/meter^2 STANDARD_DEVIATION 3.601 | 23.97 kilograms/meter^2 STANDARD_DEVIATION 3.315 | 27.68 kilograms/meter^2 STANDARD_DEVIATION 2.218 | 24.95 kilograms/meter^2 STANDARD_DEVIATION 3.041 | 26.37 kilograms/meter^2 STANDARD_DEVIATION 2.069 | 22.67 kilograms/meter^2 STANDARD_DEVIATION 3.647 | 25.55 kilograms/meter^2 STANDARD_DEVIATION 4.157 | 25.37 kilograms/meter^2 STANDARD_DEVIATION 2.914 | 23.23 kilograms/meter^2 STANDARD_DEVIATION 2.319 | 24.15 kilograms/meter^2 STANDARD_DEVIATION 4.097 | 22.88 kilograms/meter^2 STANDARD_DEVIATION 2.785 | 24.92 kilograms/meter^2 STANDARD_DEVIATION 3.369 |
| Body weight | 80.15 kilograms STANDARD_DEVIATION 12.279 | 73.88 kilograms STANDARD_DEVIATION 12.495 | 83.48 kilograms STANDARD_DEVIATION 12.015 | 81.25 kilograms STANDARD_DEVIATION 15.486 | 85.20 kilograms STANDARD_DEVIATION 8.323 | 62.17 kilograms STANDARD_DEVIATION 14.016 | 75.12 kilograms STANDARD_DEVIATION 17.688 | 77.77 kilograms STANDARD_DEVIATION 15.225 | 65.91 kilograms STANDARD_DEVIATION 7.416 | 72.6 kilograms STANDARD_DEVIATION 18.304 | 66.73 kilograms STANDARD_DEVIATION 11.898 | 74.62 kilograms STANDARD_DEVIATION 14.251 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants | 6 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 172.58 centimeters STANDARD_DEVIATION 9.031 | 175.32 centimeters STANDARD_DEVIATION 7.802 | 173.48 centimeters STANDARD_DEVIATION 11.127 | 180.05 centimeters STANDARD_DEVIATION 6.293 | 179.65 centimeters STANDARD_DEVIATION 4.281 | 165.20 centimeters STANDARD_DEVIATION 10.623 | 170.87 centimeters STANDARD_DEVIATION 12.692 | 174.90 centimeters STANDARD_DEVIATION 17.24 | 168.37 centimeters STANDARD_DEVIATION 6.033 | 172.35 centimeters STANDARD_DEVIATION 9.957 | 170.47 centimeters STANDARD_DEVIATION 7.277 | 172.54 centimeters STANDARD_DEVIATION 10.192 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 4 Participants | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 5 Participants | 58 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 5 Participants | 1 Participants | 3 Participants | 26 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 6 Participants | 2 Participants | 5 Participants | 3 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 10 | 0 / 2 | 1 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 0 / 6 | 1 / 6 | 3 / 7 | 3 / 7 | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part A (SAD): Number of Participants With Abnormal ECG
The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec.
Time frame: Part A (SAD): Screening up to Day 3
Population: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any results for the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Results for the 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed)'.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 16 mg (Fed) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 48 mg (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 60 mg (Fasted) | Part A (SAD): Number of Participants With Abnormal ECG | 0 Participants |
Primary
Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs
The number of participants with clinically significant abnormalities in vital signs is presented. Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature
Time frame: Part A (SAD): Screening up to Day 3
Population: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any results for the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Results for the 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed)'.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 16 mg (Fed) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 48 mg (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 60 mg (Fasted) | Part A (SAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Primary
Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations
The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented.
Time frame: Part A (SAD): Screening up to Day 3
Population: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any results for the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Results for the 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed)'.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 16 mg (Fed) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 48 mg (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
| Part A (SAD): 60 mg (Fasted) | Part A (SAD): Number of Subjects With Clinically Significant Changes in Laboratory Evaluations | 0 Participants |
Primary
Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant
The number of participants who experienced a treatment-emergent event (TEAE) are presented.
Time frame: Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts
Population: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any AEs experienced by the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Any AEs experienced by these 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 1 Participants |
| Part A (SAD): Placebo (Fed) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 1 Participants |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 2 Participants |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 1 Participants |
| Part A (SAD): 16 mg (Fed) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 2 Participants |
| Part A (SAD): 48 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 0 Participants |
| Part A (SAD): 60 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 1 Participants |
Primary
Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced
The number of total events experienced by participants are presented.
Time frame: Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts
Population: Safety population. The 'Part A (SAD): Placebo (Fasted)' cohort includes the 8 participants in the fasted only cohort as well as any AEs experienced by the 2 participants in the 'Part A (SAD): Placebo (Fasted/Fed)' cohort whilst in the fasting during Treatment Period 1. Any AEs experienced by these 2 participants during Treatment Period 2 (ie, the fed stage) only are listed separately under the cohort 'Part A (SAD): Placebo (Fed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 1 events |
| Part A (SAD): Placebo (Fed) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 0 events |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 1 events |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 2 events |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 2 events |
| Part A (SAD): 16 mg (Fed) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 3 events |
| Part A (SAD): 48 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 0 events |
| Part A (SAD): 60 mg (Fasted) | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 1 events |
Primary
Part B (MAD): Number of Participants With Abnormal ECG
The number of participants with abnormal electrocardiogram (ECG) results is presented. Abnormal ECGs were considered to be those with a QTcF interval of greater than 450 msec for males and greater than 470 msec for females, or change from baseline of greater than 30 msec.
Time frame: Part B (MAD): Screening up to Day 14(±3)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Participants With Abnormal ECG | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Participants With Abnormal ECG | 0 Participants |
Primary
Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs
The number of participants with clinically significant abnormalities in vital signs is presented. Vital signs: systolic and diastolic blood pressure, pulse rate, and oral body temperature
Time frame: Part B (MAD): Screening up to Day 14(±3)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Primary
Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations
The number of participants with clinically significant changes in any laboratory evaluations (clinical chemistry, haematology, coagulation, or urinalysis) is presented.
Time frame: Part B (MAD): Screening up to Day 14(±3)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in leukocyte count (to above the reference range) | 0 Participants |
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in any other evaluation | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in any other evaluation | 0 Participants |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in leukocyte count (to above the reference range) | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in leukocyte count (to above the reference range) | 0 Participants |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in any other evaluation | 0 Participants |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in leukocyte count (to above the reference range) | 1 Participants |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Participants With Clinically Significant Changes in Laboratory Evaluations | Change in any other evaluation | 0 Participants |
Primary
Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant
The number of participants who experienced a treatment-emergent event (TEAE) are presented.
Time frame: Part B (MAD): Screening up to Day 14(±3)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 3 Participants |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 3 Participants |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 3 Participants |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) by Participant | 3 Participants |
Primary
Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced
The number of total TEAE events experienced by participants are presented.
Time frame: Part B (MAD): Screening up to Day 14(±3)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 7 events |
| Part A (SAD): Placebo (Fed) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 6 events |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 8 events |
| Part A (SAD): 9 mg (Fasted) | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | 4 events |
Secondary
Part A (SAD) - Difference in Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity in Fasted State and in Fed State
Difference in area under the concentration time curve from time 0 extrapolated to infinity derived from plasma concentration-time profile of AQ280 in fasted state and in fed state to assess the effect of food on single oral doses of 16 mg AQ280. The within-subject coefficient of variation is presented under the 16 mg fed results.
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population of the 16mg fed and fasted groups in Part A. No other dose groups were assessed for food effect.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Difference in Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity in Fasted State and in Fed State | 539 h*ng/mL | — |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Difference in Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity in Fasted State and in Fed State | 527 h*ng/mL | Geometric Coefficient of Variation 5.66 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess the Effect of Food on Single Oral Doses of 16 mg AQ28090% CI: [0.915, 1.04]
Secondary
Part A (SAD) - Difference in Maximum Observed Concentration (Cmax) in Fasted State and in Fed State
Difference in maximum observed concentration (Cmax) derived from plasma concentration-time profile of AQ280 in fasted state and in fed state to assess the effect of food on single oral doses of 16 mg AQ280. The within-subject coefficient of variation is presented under the 16 mg fed results.
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population of the 16mg fed and fasted groups in Part A. No other dose groups were assessed for food effect.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Difference in Maximum Observed Concentration (Cmax) in Fasted State and in Fed State | 113 ng/mL | — |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Difference in Maximum Observed Concentration (Cmax) in Fasted State and in Fed State | 90.8 ng/mL | Geometric Coefficient of Variation 20.5 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess the Effect of Food on Single Oral Doses of 16 mg AQ28090% CI: [0.635, 1.02]
Secondary
Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax)
Part A (SAD) - Primary PK parameter derived from plasma concentration-time profile of AQ280: maximum observed concentration (Cmax) following Single Oral Dose Administration of 3, 9, 16, 48, and 60 mg AQ280 in a Fasted State and 16 mg AQ280 in a Fed State
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 20.0 ng/mL | Geometric Coefficient of Variation 16.1 |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 70.1 ng/mL | Geometric Coefficient of Variation 25.1 |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 113 ng/mL | Geometric Coefficient of Variation 16.5 |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 90.8 ng/mL | Geometric Coefficient of Variation 19.6 |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 418 ng/mL | Geometric Coefficient of Variation 40.8 |
| Part A (SAD): 16 mg (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | 638 ng/mL | Geometric Coefficient of Variation 23.3 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 3 to 60 mg AQ280p-value: 0.365395% CI: [1.04, 1.22]Lack of Fit 2-sided
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280p-value: 0.293395% CI: [1.01, 1.31]Lack of Fit 2-sided
Secondary
Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity
Area under the concentration time curve from time 0 extrapolated to infinity of metabolite AQ282 following single oral dose administration of 3, 9, 16, 48, and 60 mg AQ280 in a fasted state and 16 mg AQ280 in a fed state
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | NA h*ng/mL | — |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 32.7 h*ng/mL | Geometric Coefficient of Variation 28.2 |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 43.7 h*ng/mL | Geometric Coefficient of Variation 68.9 |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 45.1 h*ng/mL | Geometric Coefficient of Variation 66.4 |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 239 h*ng/mL | Geometric Coefficient of Variation 75.8 |
| Part A (SAD): 16 mg (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 210 h*ng/mL | Geometric Coefficient of Variation 82 |
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 3 to 60 mg AQ280p-value: 0.4695% CI: [0.908, 1.41]Lack of Fit 2-sided
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280p-value: 0.315795% CI: [0.795, 1.45]Lack of Fit 2-sided
Secondary
Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax) of metabolite AQ282 following single oral dose administration of 3, 9, 16, 48, and 60 mg AQ280 in a fasted state and 16 mg AQ280 in a fed state
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 0.722 ng/mL | Geometric Coefficient of Variation 34.4 |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 3.38 ng/mL | Geometric Coefficient of Variation 22.4 |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 3.91 ng/mL | Geometric Coefficient of Variation 55.9 |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 3.84 ng/mL | Geometric Coefficient of Variation 62.4 |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 24.4 ng/mL | Geometric Coefficient of Variation 81.2 |
| Part A (SAD): 16 mg (Fed) | Part A (SAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | 24.4 ng/mL | Geometric Coefficient of Variation 64.8 |
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 3 to 60 mg AQ280p-value: 0.23595% CI: [1.02, 1.37]Lack of fit 1-sided p-value
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280p-value: 0.163295% CI: [0.88, 1.5]Lack of fit 1-sided p-value
Secondary
Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity
Primary PK parameters derived from plasma concentration-time profile of AQ280: area under the concentration time curve from time 0 extrapolated to infinity following Single Oral Dose Administration of 3, 9, 16, 48, and 60 mg AQ280 in a Fasted State and 16 mg AQ280 in a Fed State
Time frame: Days 1, 2 and 3
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 77.0 h*ng/mL | Geometric Coefficient of Variation 17.2 |
| Part A (SAD): Placebo (Fed) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 318 h*ng/mL | Geometric Coefficient of Variation 23.8 |
| Part A (SAD): 3 mg (Fasted) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 539 h*ng/mL | Geometric Coefficient of Variation 35.4 |
| Part A (SAD): 9 mg (Fasted) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 527 h*ng/mL | Geometric Coefficient of Variation 33.7 |
| Part A (SAD): 16 mg (Fasted) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 1860 h*ng/mL | Geometric Coefficient of Variation 43.2 |
| Part A (SAD): 16 mg (Fed) | Part A (SAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity | 2820 h*ng/mL | Geometric Coefficient of Variation 26.5 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 3 to 60 mg AQ280p-value: 0.635895% CI: [1.07, 1.27]Lack of fit 2-sided
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280p-value: 0.550695% CI: [0.963, 1.31]Lack of Fit 2-sided
Secondary
Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ)
Area under the concentration time curve over a dosing interval (AUCτ) of metabolite AQ282 following single oral dose administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7).
Time frame: Day 1 and Day 7
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 1 | 31.3 h*ng/mL | Geometric Coefficient of Variation 33.7 |
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 7 | 37.0 h*ng/mL | Geometric Coefficient of Variation 29.7 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 1 | 121 h*ng/mL | Geometric Coefficient of Variation 43.1 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 7 | 123 h*ng/mL | Geometric Coefficient of Variation 61 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 1 | 217 h*ng/mL | Geometric Coefficient of Variation 44.4 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Area Under the Concentration Time Curve Over a Dosing Interval (AUCτ) | Day 7 | 214 h*ng/mL | Geometric Coefficient of Variation 71.6 |
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Multiple Oral Doses of 9 to 60 mg AQ280 once daily for 7 Consecutive Days in a Fasted Statep-value: 0.485695% CI: [0.602, 1.28]Lack of fit 2-sided
Secondary
Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax) of metabolite AQ282 following single oral dose administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7).
Time frame: Day 1 and Day 7
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 1 | 3.37 ng/mL | Geometric Coefficient of Variation 25.3 |
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 7 | 3.59 ng/mL | Geometric Coefficient of Variation 15.9 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 1 | 15.6 ng/mL | Geometric Coefficient of Variation 35.1 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 7 | 14.2 ng/mL | Geometric Coefficient of Variation 53 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 1 | 24.6 ng/mL | Geometric Coefficient of Variation 35.9 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameter Derived From Plasma Concentration-time Profile of the AQ280 Main Metabolite, AQ282: Maximum Observed Concentration (Cmax) | Day 7 | 21.3 ng/mL | Geometric Coefficient of Variation 61.1 |
Comparison: Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Multiple Oral Doses of 9 to 60 mg AQ280 once daily for 7 Consecutive Days in a Fasted Statep-value: 0.145595% CI: [0.666, 1.28]Lack of fit 2-sided
Secondary
Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR)
Accumulation ratio (AR) AQ280 following multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state on Day 7. ARAUC = accumulation ratio based on area under the concentration-time curve over a dosing interval ARCmax = accumulation ratio based on maximum observed concentration
Time frame: Day 1 to Day 7
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARAUC | 1.13 ratio | Geometric Coefficient of Variation 12 |
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARCmax | 1.11 ratio | Geometric Coefficient of Variation 22.7 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARAUC | 1.03 ratio | Geometric Coefficient of Variation 11.4 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARCmax | 0.910 ratio | Geometric Coefficient of Variation 20 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARAUC | 1.12 ratio | Geometric Coefficient of Variation 5.5 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Accumulation Ratio (AR) | ARCmax | 1.12 ratio | Geometric Coefficient of Variation 13.1 |
Secondary
Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval
Area under the concentration time curve over a dosing interval (AUCτ) following single oral administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and after multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7).
Time frame: Day 1 and Day 7
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 1 | 300 h*ng/mL | Geometric Coefficient of Variation 28.9 |
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 7 | 345 h*ng/mL | Geometric Coefficient of Variation 26.1 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 1 | 978 h*ng/mL | Geometric Coefficient of Variation 29.8 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 7 | 1000 h*ng/mL | Geometric Coefficient of Variation 21.7 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 1 | 2910 h*ng/mL | Geometric Coefficient of Variation 36.8 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Area Under the Concentration Time Curve Over a Dosing Interval | Day 7 | 3150 h*ng/mL | Geometric Coefficient of Variation 36.4 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Multiple Oral Doses of 9 to 60 mg AQ280 QD for 7 Consecutive Days in a Fasted Statep-value: 0.155895% CI: [0.954, 1.34]Lack of fit 2-sided
Secondary
Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax) following single oral administration of 9, 27, and 60 mg AQ280 in a fasted state (Day 1) and after multiple oral dose administration of 9, 27, and 60 mg AQ280 once daily for 7 consecutive days in a fasted state (Day 7).
Time frame: Day 1 and Day 7
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 1 | 64.5 ng/mL | Geometric Coefficient of Variation 30.1 |
| Part A (SAD): Placebo (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 7 | 72.0 ng/mL | Geometric Coefficient of Variation 23 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 1 | 248 ng/mL | Geometric Coefficient of Variation 24.3 |
| Part A (SAD): Placebo (Fed) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 7 | 226 ng/mL | Geometric Coefficient of Variation 20.5 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 1 | 560 ng/mL | Geometric Coefficient of Variation 32.1 |
| Part A (SAD): 3 mg (Fasted) | Part B (MAD) - Primary PK Parameters Derived From Plasma Concentration-time Profile of AQ280: Maximum Observed Concentration (Cmax) | Day 7 | 590 ng/mL | Geometric Coefficient of Variation 28.8 |
Comparison: Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Multiple Oral Doses of 9 to 60 mg AQ280 QD for 7 Consecutive Days in a Fasted Statep-value: 0.545895% CI: [0.946, 1.26]Lack of Fit 2-sided model