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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A (SAD): Group A1 | Experimental | Single dose of AQ280, 3 mg or placebo |
|
| Part A (SAD): Group A2 | Experimental | Single dose of AQ280, dose to be determined (TBD) or placebo |
|
| Part A (SAD): Group A3 | Experimental | Single dose of AQ280, dose TBD or placebo |
|
| Part A (SAD): Group A4 | Experimental | Single dose of AQ280, dose TBD or placebo |
|
| Part A (SAD): Group A5 | Experimental | Single dose of AQ280, dose TBD or placebo |
|
| Part B (MAD): Group B1 | Experimental | AQ280 dose TBD or placebo, once daily (QD) for seven days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AQ280 | Drug | Dose form: capsule, hard Strength: 3 to 100 mg Method of administration: oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts |
| Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | The number of total events experienced by participants are presented. | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts |
| 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. | Part B (MAD): Screening up to Day 14(±3) |
| Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | The number of total TEAE events experienced by participants are presented. | Part B (MAD): Screening up to Day 14(±3) |
| 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 | Part A (SAD): Screening up to Day 3 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Subjects must satisfy all of the following criteria at the screening visit (and/or at check-in, where noted):
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
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).
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee).
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.
History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose of IMP.
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values >1.2 × upper limit of normal (ULN).
Congenital nonhemolytic hyperbilirubinemia (including suspicion of Gilbert's syndrome).
Hemoglobin value, neutrophil count, and/or lymphocyte count <lower limit of normal.
Clinically significant abnormal ECG at screening or check-in.
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
Current active tuberculosis based on Quantiferon™ tuberculosis Gold test.
Prior/concomitant therapy
Administration of a coronavirus disease 2019 vaccine in the past 30 days prior to the first dose of investigational medicinal product (IMP).
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).
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).
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).
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
Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
Have previously completed or withdrawn from this study.
Diet and lifestyle
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.
Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in.
History of alcoholism or drug/chemical abuse within 2 years prior to check-in.
Smoking >5 cigarettes per day, on average, or use the equivalent tobacco- or nicotine containing products per day.
Ingestion of poppy seed , Seville orange , star fruit-, or grapefruit containing foods or beverages within 7 days prior to check-in.
Other exclusions
Receipt of blood products within 2 months prior to check-in.
Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
Poor peripheral venous access.
Subjects who, in the opinion of the investigator (or designee), should not participate in this study.
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| Name | Affiliation | Role |
|---|---|---|
| Jan Törnell, MD, PhD | AQILION AB | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fortrea Clinical Research Unit Ltd. | Leeds | LS2 9LH | United Kingdom |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A (SAD): Placebo (Fasted) | Single dose of placebo, fasted Dose form: capsule, hard Method of administration: oral |
| FG001 | Part A (SAD): 3 mg (Fasted) | Single dose of 3 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| FG002 | Part A (SAD): 9 mg (Fasted) | Single dose of 9 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | Part A (SAD): 48 mg (Fasted) | Single dose of 48 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| FG006 | Part A (SAD): 60 mg (Fasted) | Single dose of 60 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| FG007 | Part B (MAD): Placebo | Placebo, once daily (QD) for seven days Dose form: capsule, hard Method of administration: oral |
| FG008 | Part B (MAD): 9 mg | AQ280 9 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| FG009 | Part B (MAD): 27 mg | AQ280 27 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| FG010 | Part B (MAD): 60 mg | AQ280 60 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Fasted) |
|
| ||||||||||||||||||
| Treatment Period 2 (Fed Groups Only) |
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A (SAD): Placebo (Fasted) | Single dose of placebo, fasted Dose form: capsule, hard Method of administration: oral |
| BG001 | Part A (SAD): 3 mg (Fasted) | Single dose of 3 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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). | Posted | Count of Participants | Participants | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts |
|
Part A: up to 7 weeks, from screening up to safety follow up Part B: up to 8 weeks, from screening up to safety follow up
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A (SAD): Placebo (Fasted) | Single dose of placebo, fasted Dose form: capsule, hard Method of administration: oral |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anneli Tinnerholm | AQILION AB | +46 730 88 14 15 | anneli.tinnerholm@aqilion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 30, 2023 | Mar 21, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 2, 2022 | Mar 21, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D057765 | Eosinophilic Esophagitis |
| ID | Term |
|---|---|
| D004941 | Esophagitis |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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|
| Part B (MAD): Group B2 | Experimental | AQ280 dose TBD or placebo, once daily (QD) for seven days |
|
| Part B (MAD): Group B3 | Experimental | AQ280 dose TBD or placebo, once daily (QD) for seven days |
|
| Placebo | Drug | Active substance: none Dose form: capsule, hard Strength/dose: not applicable Method of administration: oral |
|
| Part A (SAD): Screening up to Day 3 |
| 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. | Part A (SAD): Screening up to Day 3 |
| 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 | Part B (MAD): Screening up to Day 14(±3) |
| 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. | Part B (MAD): Screening up to Day 14(±3) |
| 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. | Part B (MAD): Screening up to Day 14(±3) |
| Days 1, 2 and 3 |
| 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 | Days 1, 2 and 3 |
| 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 | Days 1, 2 and 3 |
| 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 | Days 1, 2 and 3 |
| 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. | Days 1, 2 and 3 |
| 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. | Days 1, 2 and 3 |
| 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 | Day 1 to Day 7 |
| 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). | Day 1 and Day 7 |
| 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). | Day 1 and 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) | 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). | Day 1 and Day 7 |
| 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). | Day 1 and Day 7 |
| Physician Decision |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | Part A (SAD): 9 mg (Fasted) | Single dose of 9 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | Part A (SAD): 48 mg (Fasted) | Single dose of 48 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| BG006 | Part A (SAD): 60 mg (Fasted) | Single dose of 60 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| BG007 | Part B (MAD): Placebo | Placebo, once daily (QD) for seven days Dose form: capsule, hard Method of administration: oral |
| BG008 | Part B (MAD): 9 mg | AQ280 9 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| BG009 | Part B (MAD): 27 mg | AQ280 27 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| BG010 | Part B (MAD): 60 mg | AQ280 60 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral |
| BG011 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Body weight | Mean | Standard Deviation | kilograms |
|
| Body mass index | Mean | Standard Deviation | kilograms/meter^2 |
|
| OG001 | Part A (SAD): Placebo (Fed) | Single dose of placebo, fed Dose form: capsule, hard Method of administration: oral |
| OG002 | Part A (SAD): 3 mg (Fasted) | Single dose of 3 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| OG003 | Part A (SAD): 9 mg (Fasted) | Single dose of 9 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| OG004 | Part A (SAD): 16 mg (Fasted) | Single dose of 16 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| OG005 | Part A (SAD): 16 mg (Fed) | Single dose of 16 mg AQ280, fed AQ280: Dose form: capsule, hard Method of administration: oral |
| OG006 | Part A (SAD): 48 mg (Fasted) | Single dose of 48 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
| OG007 | Part A (SAD): 60 mg (Fasted) | Single dose of 60 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral |
|
|
| Primary | Part A (SAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | The number of total events experienced by participants are presented. | 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). | Posted | Number | events | Part A (SAD): Screening up to Day 8 for fasted cohorts and Day 18(±2) for fed/fasted cohorts |
|
|
|
| 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. | Safety Population | Posted | Count of Participants | Participants | Part B (MAD): Screening up to Day 14(±3) |
|
|
|
| Primary | Part B (MAD): Number of Treatment Emergent Adverse Events (TEAEs) Experienced | The number of total TEAE events experienced by participants are presented. | Safety Population | Posted | Number | events | Part B (MAD): Screening up to Day 14(±3) |
|
|
|
| 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 | 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)'. | Posted | Count of Participants | Participants | Part A (SAD): Screening up to Day 3 |
|
|
|
| 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. | 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)'. | Posted | Count of Participants | Participants | Part A (SAD): Screening up to Day 3 |
|
|
|
| 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. | 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)'. | Posted | Count of Participants | Participants | Part A (SAD): Screening up to Day 3 |
|
|
|
| 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 | Safety population | Posted | Count of Participants | Participants | Part B (MAD): Screening up to Day 14(±3) |
|
|
|
| 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. | Safety population | Posted | Count of Participants | Participants | Part B (MAD): Screening up to Day 14(±3) |
|
|
|
| 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. | Safety population | Posted | Count of Participants | Participants | Part B (MAD): Screening up to Day 14(±3) |
|
|
|
| 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 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1, 2 and 3 |
|
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|
| 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 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1, 2 and 3 |
|
|
|
|
| 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 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1, 2 and 3 |
|
|
|
|
| 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 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 1, 2 and 3 |
|
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| 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. | Pharmacokinetic population of the 16mg fed and fasted groups in Part A. No other dose groups were assessed for food effect. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | h*ng/mL | Days 1, 2 and 3 |
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| 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. | Pharmacokinetic population of the 16mg fed and fasted groups in Part A. No other dose groups were assessed for food effect. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | ng/mL | Days 1, 2 and 3 |
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| 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 | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Day 1 to Day 7 |
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| 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). | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1 and Day 7 |
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| 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). | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 and Day 7 |
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| 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). | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1 and Day 7 |
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| 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). | Pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 and Day 7 |
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| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
| EG001 | Part A (SAD): Placebo (Fed) | Single dose of placebo, fed Dose form: capsule, hard Method of administration: oral | 0 | 2 | 0 | 2 | 0 | 2 |
| EG002 | Part A (SAD): 3 mg (Fasted) | Single dose of 3 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Part A (SAD): 9 mg (Fasted) | Single dose of 9 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Part A (SAD): 16 mg (Fasted) | Single dose of 16 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Part A (SAD): 16 mg (Fed) | Single dose of 16 mg AQ280, fed AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 2 | 6 |
| EG006 | Part A (SAD): 48 mg (Fasted) | Single dose of 48 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 0 | 6 |
| EG007 | Part A (SAD): 60 mg (Fasted) | Single dose of 60 mg AQ280, fasted AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 1 | 6 |
| EG008 | Part B (MAD): Placebo | Placebo, once daily (QD) for seven days Dose form: capsule, hard Method of administration: oral | 0 | 7 | 0 | 7 | 3 | 7 |
| EG009 | Part B (MAD): 9 mg | AQ280 9 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 7 | 0 | 7 | 3 | 7 |
| EG010 | Part B (MAD): 27 mg | AQ280 27 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 3 | 6 |
| EG011 | Part B (MAD): 60 mg | AQ280 60 mg once daily (QD) for seven days AQ280: Dose form: capsule, hard Method of administration: oral | 0 | 6 | 0 | 6 | 3 | 6 |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Hyperaesthesia teeth | Gastrointestinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Vessel puncture site reaction | General disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Lumbar radiculopathy | Nervous system disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA Version 25.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA Version 25.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA Version 25.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 25.0 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA Version 25.0 | Systematic Assessment |
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The results of this study may be published or presented at scientific meetings. If foreseen, the PI agrees to submit all manuscripts or abstracts to the sponsor before submission.
The sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data.
| D005759 |
| Gastroenteritis |
| D004802 | Eosinophilia |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Change in any other evaluation |
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Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280 | Lack of Fit 2-sided | Lack of Fit Model: ln(parameter) = intercept + slope × ln(dose) + dose + random error | 0.5506 | Slope | 1.13 | 2-Sided | 95 | 0.963 | 1.31 | Between-subject geometric coefficient of variation was 32.9. Data were analyzed using a power model. ln(parameter) = intercept + slope ×ln(dose) + random error. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Statistical Analysis of AQ280 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280 | Lack of Fit 2-sided | Lack of Fit Model: ln(parameter) = intercept + slope × ln(dose) + dose + random error | 0.2933 | Slope | 1.16 | 2-Sided | 95 | 1.01 | 1.31 | Between-subject geometric coefficient of variation was 27.7. Data were analyzed using a power model. ln(parameter) = intercept + slope ×ln(dose) + random error | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280 | Lack of Fit 2-sided | Lack of Fit Model: ln(parameter) = intercept + slope × ln(dose) + dose + random error | 0.3157 | Slope | 1.12 | 2-Sided | 95 | 0.795 | 1.45 | Between-subject geometric coefficient of variation was 65.6. Data were analyzed using a power model. ln(parameter) = intercept + slope ×ln(dose) + random error | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Statistical Analysis of Metabolite AQ282 Primary Pharmacokinetic Endpoints to Assess Dose Proportionality of Single Oral Doses of 9 to 60 mg AQ280 | Lack of fit 1-sided p-value | Lack of Fit Model: ln(parameter) = intercept + slope × ln(dose) + dose + random error | 0.1632 | Slope | 1.19 | 2-Sided | 95 | 0.880 | 1.50 | Between-subject geometric coefficient of variation was 58.5. Data were analyzed using a power model. ln(parameter) = intercept + slope ×ln(dose) + random error. | Equivalence | Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
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| Day 7 |
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Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Day 7 |
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Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Day 7 |
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Study was not powered and confidence intervals were assessed for containing unity (1) within them. |
| Day 7 |
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Study was not powered and confidence intervals were assessed for containing unity (1) within them. |