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A Study of the Safety, Tolerability, Pharmacokinetics and Food Effect After Single and Multiple Ascending Oral Doses

A Randomised, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, and Pharmacokinetics of AX-158 Following Administration of Single and, Multiple Ascending Oral Doses and Food Effect Sub-study in Healthy Male Volunteers

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05218434
Enrollment
64
Registered
2022-02-01
Start date
2021-11-17
Completion date
2022-12-03
Last updated
2024-08-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autoimmune Diseases

Brief summary

This is a Phase I Healthy volunteer study with the primary objective to evaluate the safety and pharmacokinetics profile of AX-158. The first part will evaluate single ascending dose administrations. A substudy will be performed as well to evaluate possible impact of food on drug exposure if administered under fasted or fed state. The second part will evaluate multiple ascending dose over 10 days of dosing in fed or fast state depending on the results of the substudy food effect on AX-158.

Detailed description

This is a phase I, randomised, double-blind , placebo controlled study to investigate the safety, tolerability, and PK of AX-158 in healthy male participants following single (Part A) and multiple (Part C) ascending doses including food effect (Part B).The study will be conducted in three parts (Part A, Part B and Part C). Part A will enrol 8 participants per cohort randomised (3 :1) to receive AX-158 (6 participants) or placebo (2 participants). Part A will follow a single ascending dose (SAD) design with all participants receiving one dose of AX-158 (or placebo) in the fasted state. Part B (Food Effect) will be conducted in 8 participants in a cross-over manner; each participant will receive AX-158 in the fed and fasted state. Part C will enrol 8 participants per cohort randomised to (3 :1) to receive AX-158 (6 participants) or placebo (2 participants). Part C will follow a multiple ascending dose (MAD) design with participants receiving AX-158 (or placebo) once daily for 10 consecutive days, in a fed or fasted state (depending on the outcome of the Part B (Food Effect).

Interventions

DRUGAX-158

Oral administrations of AX-158

Sponsors

Simbec-Orion Group
CollaboratorINDUSTRY
Artax Biopharma Inc
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

1. Healthy Male participant, between 18 and 50 years of age, inclusive. 2. Male participant (and partner of childbearing potential) willing to use a highly effective method of contraception in addition to a condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from first dose until 4 months after last dose of Investigational Medicinal Product (IMP). 3. Participant with a body mass index (BMI) of 18-30kg/m2. BMI = body weight (kg) / \[height (m)\]2. 4. Total serum bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x upper limit of normal (ULN). If total bilirubin is above the upper limit of normal and is then fractionated, direct bilirubin must be within normal limits. 5. Total serum Testosterone levels 2 x above the lower limit of the normal range within 28 days before the first dose administration of the IMP. 6. Participant with a negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP (N.B.: A positive test result may be repeated at the Investigator's discretion). 7. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg)) and hepatitis C virus antibody (HCV Ab) test results at Screening. 8. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP including a QRS interval \> 120ms, PR interval \> 220ms and QTcF \> 450ms. 9. No clinically significant abnormalities in vital signs (e.g., blood pressure/pulse rate, respiration rate and oral temperature) determined within 28 days before first dose of IMP. 10. Participant must be available to complete the study (including all follow-up visits). 11. Participant must satisfy an Investigator about his fitness to participate in the study. 12. Participant must provide written informed consent to participate in the study. 13. Participants with a negative COVID-19 PCR test on admission.

Exclusion criteria

1. A clinically significant history of gastrointestinal disorder likely to influence IMP absorption. 2. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP. Occasional use of paracetamol will be allowed. 3. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction. 4. Clinically significant history of previous allergy / sensitivity to AX-158 or any of the excipients contained within the IMP. 5. Participant with history of autoimmune disease, cardiac disease, kidney disease or any food intolerance. 6. Participants with clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP 7. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units \[for male and female participants\] of alcohol a week) within the past two years. 8. Inability to communicate well with the Investigators (i.e., language problem, poor mental development, or impaired cerebral function). 9. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within the 30 days or five half-lives, whichever is longer, before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study). 10. Donation of 450 milliliters or more blood within the 3 months before the first dose of IMP. 11. Vegans, vegetarians, or other dietary restrictions (e.g., restrictions for medical, religious, or cultural reasons, etc), which would prevent participants from consuming a high-fat breakfast or standardised meal. 12. Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to screening or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums). 13. Participants who have received a COVID-19 vaccine injection within 28 days prior to the first dose of IMP.

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Treatment-Emergent Adverse EventsUp to 10 days of treatmentThe number of participants with recorded treatment emergent adverse events following single and multiple doses of AX-158.

Secondary

MeasureTime frameDescription
Maximal Plasma Concentration (Cmax)Up to 13 days following dose administrationValues calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose
Total Plasma Drug Exposure (AUC0-t)Up to 13 days following dose administrationValues calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose
Terminal Half Life (t1/2)Up to 13 days following dose administrationValues calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose

Countries

United Kingdom

Participant flow

Recruitment details

Study recruitment for this study was undertaken in South Wales in the United Kingdom. A sufficient number of participants were screened in order to successfully recruit 64 eligible participants.

Pre-assignment details

Volunteers were screened to the inclusion/exclusion criteria of the study protocol. The following assessments were performed: Physical exam, Demographics,ECG,Vital signs, Safety Laboratory testing/Urinalysis.

Participants by arm

ArmCount
Part A - 5mg AX-158
Single Oral Dose of 5 mg AX-158 administered on Day 1
6
Part A - 10mg AX-158
Single Oral Dose of 10 mg AX-158 administered on Day 1
5
Part A - 15mg AX-158
Single Oral Dose of 15 mg AX-158 administered on Day 1
4
Part A - 25mg AX-158
Single Oral Dose of 25 mg AX-158 administered on Day 1
4
Part A - 50mg AX-158
Single Oral Dose of 50 mg AX-158 administered on Day 1
6
Part A - Placebo
Denotes participants across all Part A cohorts who received matching placebo.
9
Part B - 15mg AX-158 Fed/Fasted
Single Oral Dose of 15 mg AX-158 administered on Day 1 of treatment period 1 in the fed state following a high-fat breakfast and administered on Day 1 in a fasted state in treatment period 2.
8
Part C - 5mg AX-158
Single Oral Dose of 5 mg AX-158 administered once daily from Day 1 to Day 10
6
Part C - 10mg AX-158
Single Oral Dose of 10 mg AX-158 administered once daily from Day 1 to Day 10
5
Part C - 15mg AX-158
Single Oral Dose of 15 mg AX-158 administered once daily from Day 1 to Day 10
6
Part C - Placebo
Denotes participants across all Part C cohorts who received matching placebo.
5
Total64

Baseline characteristics

CharacteristicPart A - 10mg AX-158Part A - 15mg AX-158Part A - 25mg AX-158Part A - 50mg AX-158Part A - PlaceboPart B - 15mg AX-158 Fed/FastedPart A - 5mg AX-158Part C - 5mg AX-158Part C - 10mg AX-158Part C - 15mg AX-158Part C - PlaceboTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
5 Participants4 Participants4 Participants6 Participants9 Participants8 Participants6 Participants6 Participants5 Participants6 Participants5 Participants64 Participants
BMI25.880 kg/m2
STANDARD_DEVIATION 2.0092
23.580 kg/m2
STANDARD_DEVIATION 2.8956
25.548 kg/m2
STANDARD_DEVIATION 2.5745
24.313 kg/m2
STANDARD_DEVIATION 1.369
25.557 kg/m2
STANDARD_DEVIATION 3.3519
26.850 kg/m2
STANDARD_DEVIATION 3.0544
25.508 kg/m2
STANDARD_DEVIATION 2.1783
24.053 kg/m2
STANDARD_DEVIATION 3.2247
24.392 kg/m2
STANDARD_DEVIATION 3.0302
24.672 kg/m2
STANDARD_DEVIATION 4.5817
22.584 kg/m2
STANDARD_DEVIATION 1.5257
25.143 kg/m2
STANDARD_DEVIATION 2.485
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants4 Participants4 Participants6 Participants9 Participants8 Participants6 Participants6 Participants5 Participants6 Participants4 Participants63 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Height1.788 Metres
STANDARD_DEVIATION 0.037
1.780 Metres
STANDARD_DEVIATION 0.0594
1.783 Metres
STANDARD_DEVIATION 0.0699
1.762 Metres
STANDARD_DEVIATION 0.0436
1.783 Metres
STANDARD_DEVIATION 0.0532
1.771 Metres
STANDARD_DEVIATION 0.0617
1.800 Metres
STANDARD_DEVIATION 0.062
1.747 Metres
STANDARD_DEVIATION 0.0592
1.772 Metres
STANDARD_DEVIATION 0.0694
1.805 Metres
STANDARD_DEVIATION 0.0485
1.734 Metres
STANDARD_DEVIATION 0.0488
1.783 Metres
STANDARD_DEVIATION 0.0513
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants0 Participants0 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants4 Participants4 Participants6 Participants9 Participants8 Participants5 Participants6 Participants4 Participants6 Participants5 Participants62 Participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
5 Participants4 Participants4 Participants6 Participants9 Participants8 Participants6 Participants6 Participants5 Participants6 Participants5 Participants64 Participants
Weight82.62 Kg
STANDARD_DEVIATION 5.034
74.60 Kg
STANDARD_DEVIATION 8.636
81.53 Kg
STANDARD_DEVIATION 12.829
75.55 Kg
STANDARD_DEVIATION 6.486
81.24 Kg
STANDARD_DEVIATION 10.989
84.34 Kg
STANDARD_DEVIATION 11.244
83.2 Kg
STANDARD_DEVIATION 12.019
73.25 Kg
STANDARD_DEVIATION 9.194
76.74 Kg
STANDARD_DEVIATION 11.959
79.88 Kg
STANDARD_DEVIATION 12.015
67.78 Kg
STANDARD_DEVIATION 2.842
80.01 Kg
STANDARD_DEVIATION 9.638

Adverse events

Event typeEG000
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 / 60 / 50 / 40 / 40 / 60 / 90 / 80 / 80 / 60 / 50 / 60 / 5
other
Total, other adverse events
0 / 60 / 50 / 40 / 41 / 61 / 91 / 81 / 81 / 61 / 50 / 62 / 5
serious
Total, serious adverse events
0 / 00 / 50 / 40 / 40 / 60 / 90 / 80 / 80 / 60 / 50 / 60 / 5

Outcome results

Primary

Number of Participants With Treatment-Emergent Adverse Events

The number of participants with recorded treatment emergent adverse events following single and multiple doses of AX-158.

Time frame: Up to 10 days of treatment

ArmMeasureValue (NUMBER)
Part A - 5 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part A - 10 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part A - 15 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part A - 25 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part A - 50 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part B - 15 mg AX-158 Fed StateNumber of Participants With Treatment-Emergent Adverse Events1 participants
Part B - 15 mg AX-158 FastedNumber of Participants With Treatment-Emergent Adverse Events1 participants
Part C - 5 mg AX-158Number of Participants With Treatment-Emergent Adverse Events3 participants
Part C - 10 mg AX-158Number of Participants With Treatment-Emergent Adverse Events1 participants
Part C - 15 mg AX-158Number of Participants With Treatment-Emergent Adverse Events0 participants
Part A - PlaceboNumber of Participants With Treatment-Emergent Adverse Events1 participants
Part C - PlaceboNumber of Participants With Treatment-Emergent Adverse Events4 participants
Secondary

Maximal Plasma Concentration (Cmax)

Values calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose

Time frame: Up to 13 days following dose administration

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Part A - 5 mg AX-158Maximal Plasma Concentration (Cmax)0.0831 µg/mLGeometric Coefficient of Variation 16.3
Part A - 10 mg AX-158Maximal Plasma Concentration (Cmax)0.174 µg/mLGeometric Coefficient of Variation 9.7
Part A - 15 mg AX-158Maximal Plasma Concentration (Cmax)0.29 µg/mLGeometric Coefficient of Variation 10
Part A - 25 mg AX-158Maximal Plasma Concentration (Cmax)0.487 µg/mLGeometric Coefficient of Variation 15.8
Part A - 50 mg AX-158Maximal Plasma Concentration (Cmax)0.86 µg/mLGeometric Coefficient of Variation 18.9
Part B - 15 mg AX-158 Fed StateMaximal Plasma Concentration (Cmax)0.237 µg/mLGeometric Coefficient of Variation 20.7
Part B - 15 mg AX-158 FastedMaximal Plasma Concentration (Cmax)0.273 µg/mLGeometric Coefficient of Variation 26.3
Part C - 5 mg AX-158Maximal Plasma Concentration (Cmax)0.108 µg/mLGeometric Coefficient of Variation 7.1
Part C - 10 mg AX-158Maximal Plasma Concentration (Cmax)0.194 µg/mLGeometric Coefficient of Variation 15.4
Part C - 15 mg AX-158Maximal Plasma Concentration (Cmax)0.298 µg/mLGeometric Coefficient of Variation 17.5
Secondary

Terminal Half Life (t1/2)

Values calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose

Time frame: Up to 13 days following dose administration

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Part A - 5 mg AX-158Terminal Half Life (t1/2)8.94 hGeometric Coefficient of Variation 18.4
Part A - 10 mg AX-158Terminal Half Life (t1/2)8.48 hGeometric Coefficient of Variation 13.1
Part A - 15 mg AX-158Terminal Half Life (t1/2)8.56 hGeometric Coefficient of Variation 22.1
Part A - 25 mg AX-158Terminal Half Life (t1/2)10.6 hGeometric Coefficient of Variation 25.4
Part A - 50 mg AX-158Terminal Half Life (t1/2)9.58 hGeometric Coefficient of Variation 10.5
Part B - 15 mg AX-158 Fed StateTerminal Half Life (t1/2)8.19 hGeometric Coefficient of Variation 25.6
Part B - 15 mg AX-158 FastedTerminal Half Life (t1/2)8.44 hGeometric Coefficient of Variation 18.8
Part C - 5 mg AX-158Terminal Half Life (t1/2)9.7 hGeometric Coefficient of Variation 4.7
Part C - 10 mg AX-158Terminal Half Life (t1/2)8.41 hGeometric Coefficient of Variation 21.4
Part C - 15 mg AX-158Terminal Half Life (t1/2)9.84 hGeometric Coefficient of Variation 20.9
Secondary

Total Plasma Drug Exposure (AUC0-t)

Values calculated for derived PK parameters following samples obtained at the following timepoints: Part A & B: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, Day 2: 24 hr, 36 hr, Day 3: 48 hr & Day 4: 72 hr post-Day 1 dose Part C: Day 1: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 1 dose Day 2: 24 hr, 36 hr post-Day 1 dose Day 3: 48 hr post-Day 1 dose Day 4: 72 hr post-Day 1 dose Day 5: prior to dose Day 10: pre-dose, 30 mins, 45 mins, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr post-Day 10 dose Day 11: 24 hr, 36 hr post-Day 10 dose Day 12: 48 hr post-Day 10 dose Day 13: 72 hr post-Day 10 dose

Time frame: Up to 13 days following dose administration

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Part A - 5 mg AX-158Total Plasma Drug Exposure (AUC0-t)1.07 h*µg/mLGeometric Coefficient of Variation 35.6
Part A - 10 mg AX-158Total Plasma Drug Exposure (AUC0-t)2.06 h*µg/mLGeometric Coefficient of Variation 20.8
Part A - 15 mg AX-158Total Plasma Drug Exposure (AUC0-t)3.87 h*µg/mLGeometric Coefficient of Variation 25.2
Part A - 25 mg AX-158Total Plasma Drug Exposure (AUC0-t)6.88 h*µg/mLGeometric Coefficient of Variation 34
Part A - 50 mg AX-158Total Plasma Drug Exposure (AUC0-t)11.9 h*µg/mLGeometric Coefficient of Variation 24.6
Part B - 15 mg AX-158 Fed StateTotal Plasma Drug Exposure (AUC0-t)3.3 h*µg/mLGeometric Coefficient of Variation 36.3
Part B - 15 mg AX-158 FastedTotal Plasma Drug Exposure (AUC0-t)3.43 h*µg/mLGeometric Coefficient of Variation 34
Part C - 5 mg AX-158Total Plasma Drug Exposure (AUC0-t)1.67 h*µg/mLGeometric Coefficient of Variation 22.5
Part C - 10 mg AX-158Total Plasma Drug Exposure (AUC0-t)2.65 h*µg/mLGeometric Coefficient of Variation 38.6
Part C - 15 mg AX-158Total Plasma Drug Exposure (AUC0-t)4.97 h*µg/mLGeometric Coefficient of Variation 28.5

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026