SAD, MAD and Food Effect Evaluation of Safety, Tolerability, and PK of AQ280 in Healthy Subjects

Phase 1

Completed

Conditions: Eosinophilic Esophagitis (EoE)

Interventions: Drug: AQ280
Drug: Placebo

Registration Number: NCT05485779

Lead Sponsor: AQILION AB

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

Subjects must satisfy all of the following criteria at the screening visit (and/or at check-in, where noted):

Males or females, of any race, between 18 and 65 years of age, inclusive.
Body mass index between 18.0 and 32.0 kg/m2, inclusive.
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).
Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
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

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A (SAD): Group A3	AQ280	Single dose of AQ280, dose TBD or placebo
Part B (MAD): Group B1	AQ280	AQ280 dose TBD or placebo, once daily (QD) for seven days
Part A (SAD): Group A2	Placebo	Single dose of AQ280, dose to be determined (TBD) or placebo
Part A (SAD): Group A1	AQ280	Single dose of AQ280, 3 mg or placebo
Part A (SAD): Group A1	Placebo	Single dose of AQ280, 3 mg or placebo
Part A (SAD): Group A2	AQ280	Single dose of AQ280, dose to be determined (TBD) or placebo
Part A (SAD): Group A3	Placebo	Single dose of AQ280, dose TBD or placebo
Part A (SAD): Group A4	AQ280	Single dose of AQ280, dose TBD or placebo
Part A (SAD): Group A4	Placebo	Single dose of AQ280, dose TBD or placebo
Part A (SAD): Group A5	AQ280	Single dose of AQ280, dose TBD or placebo
Part A (SAD): Group A5	Placebo	Single dose of AQ280, dose TBD or placebo
Part B (MAD): Group B1	Placebo	AQ280 dose TBD or placebo, once daily (QD) for seven days
Part B (MAD): Group B2	AQ280	AQ280 dose TBD or placebo, once daily (QD) for seven days
Part B (MAD): Group B2	Placebo	AQ280 dose TBD or placebo, once daily (QD) for seven days
Part B (MAD): Group B3	AQ280	AQ280 dose TBD or placebo, once daily (QD) for seven days
Part B (MAD): Group B3	Placebo	AQ280 dose TBD or placebo, once daily (QD) for seven days

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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).
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).