Clinical trial NCT06019065: A SAD, MAD and Food Effect Study to Evaluate the Safety, Tolerability, PK, and PD of AJA001 in Healthy Subjects
Official title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AJA001 in Fasting and Fed Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: AJNA Australia Pty Ltd
Sponsor class: INDUSTRY
First posted: 2023-08-31
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, double-blind, randomized, placebo- controlled, SAD and MAD study to assess safety, tolerability, PK, and PD of AJA001 in fasted healthy participants. Food effect will be evaluated in one cross-over SAD fed dose cohort.

Detailed description: The study is comprised of two parts, Part A (SAD) and Part B (MAD). Participants will be randomized (active or placebo) in each cohort of Parts A and B. Participants in Part A will receive a single dose of AJA001 or placebo on Day 1. Part A will include a fed-cohort (A-X) for one cohort where the participants will return to the clinical site on Day 14 to receive AJA001 or placebo. Participants in Part B will receive a split dose of AJA001 or placebo, where one dose will be administered as two equal doses taken twice daily, (BID; administered approximately every 12 hours \[± 30 minutes\]) for 6 consecutive days (Day 1-Day 6), and 1 morning dose on Day 7.

Eligibility criteria: Inclusion Criteria:

1. Provide signed ethics committee (EC)-approved consent form prior to any study procedures, can understand and comply with the requirements of the study, and are able to communicate with the Investigator
2. Males and females, aged 18 and 65 years (inclusive), with body mass index (BMI) of 18 32.0 kg/m2 and body weight ≥50.0 kg at screening
3. No known allergic reaction to cannabis products and formulation components (Glyceryl Monolinoleate, NF and organic chocolate mint flavoring agent)
4. Medically healthy with no clinically significant medical history (fully resolved childhood asthma and mild asthma that does not require a reliever more than once per month, and does not require a preventer or any additional therapies is not considered clinically significant and permissible), physical examination, laboratory profiles, vital signs, or ECG, as deemed by the Investigator
5. Must have hepatic and renal clinical laboratory test results (ALT, AST, total bilirubin \[including direct and indirect bilirubin results\], and eGFR) within a laboratory defined normal range
6. Male participants who are not vasectomized for at least 6 months prior to dosing and who are sexually active with a female partner of childbearing potential must be willing to use one of the acceptable contraceptive methods specified below under "Contraception" in Section 8.1 from the first dose and for 90 days after the last dose
7. Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized at least 6 months prior to the first study drug administration) must be willing to use one of the acceptable contraceptive methods specified below specified below under "Contraception" throughout the study and for at least 3 months after the last study drug administration
8. Refrain from donating sperm for the duration of the study and for at least 90 days after the last dose of investigational product (IP)
9. Females must have a negative serum pregnancy test (SPT) at screening and urinary pregnancy test (UPT) at check-in on Day -1
10. Agree to frequent blood sampling during the course of the study and with adequate venous access
11. Agree to be confined for parts of the study in the Phase 1 unit and follow study procedures
12. Agree to comply with the study-specified diet while confined in the Phase 1 unit. Participants in the Part A - cohort which enter the fed cross-over design (A-X) must agree to complete consumption of a standardized high-fat breakfast during the fed period on Day 15
13. Negative drug and alcohol tests at screening and at admissions on Day -1 and willing to abstain from alcohol/illegal drug use from the screening visit until the End of Study (EOS) visit
14. Able to read, understand, provide signed informed consent, communicate adequately, and comply with the requirements for the entire study.

Exclusion Criteria:

1. Use of any medications or over the-counter (OTC) products within 10 days or 5 half lives (whichever is longer) prior to administration of study medication (including analgesics \[note: except paracetamol up to 2 g per day\], antibiotics, hormonal contraceptives\* \[except, which is permitted\], natural food supplements, vitamins, garlic as a supplement)

   \*Note: Stable doses of oral contraceptives for birth control in women of childbearing potential (WOCBP) (minimum of 3 months without issue as deemed by the Investigator) will be allowed. No other hormonal treatment will be allowed.
2. Use of an investigational drug or participation in an investigational study within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing
3. Use of known inhibitors or inducers of hepatic drug metabolism (e.g., rifampin, carbamazepine, phenytoin, norethindrone, barbiturates \[e.g., phenobarbital\], dexamethasone, antidepressants \[e.g., fluoxetine, paroxetine\], proton pump inhibitors, ketoconazole) 1 month before the start of the study (Day 1)
4. Hypersensitivity or any significant allergic reaction to the investigational compound/compound class being used in this study or any ingredients of this medication
5. Medical history or any clinically significant disorder (as determined by the Investigator and Sponsor) including but not limited to: clinically significant allergies, asthma (fully resolved childhood asthma with no reoccurrences in adulthood is permissible), angioedema, pulmonary, bronchospasm, ulcer disease, gastrointestinal (GI), GI bleeding, coagulation defects, hypertension, edema, heart failure, hypokalemia, cardiovascular disease, significant dermatologic diseases or conditions; hematological, neurological, psychiatric, hepatic, or renal disorders; condition that would significantly influence the immune response; or history of infections of unexplained frequency or severity;
6. Personal diagnosis or first-degree relative diagnosis of psychosis/schizophrenia
7. Presence of current psychiatric condition, suicide ideations or psychiatric condition requiring pharmacological management within the last 6 months
8. History or presence of any condition that, in the opinion of the Investigator, could interfere with the study conduct or observation (to be confirmed by medical history)
9. Has used any tobacco / nicotine-containing products (e.g., cigarettes, vaporizers, cigars, pipe tobacco, smokeless tobacco, nicotine gum, lozenges, patches) on more than 5 occasions within 1 month of the Screening visit
10. History of significant drug abuse within 1 year prior to screening or use of drugs such as cannabis within 2 months prior to the screening visit or drugs such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
11. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week for female participants and 21 units for male participants (1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%).
12. History of or risk for seizures (one-off febrile seizure as a child is permissible)
13. History or positive screening results to hepatitis B surface antigen or C virus Ab tests, or to human immunodeficiency virus (HIV) Ag/Ab combination, or has known immune deficiency disease at screening
14. Surgical (history of stomach or intestinal surgery or resection) or medical condition (evidence of prior chronic GI disease such a cholecystitis, cholecystectomy, Gilbert's syndrome) that would interfere with gastric motility, pH, or absorption of study drug
15. Laboratory values outside normal ranges based on the laboratory reference values and are clinically significant or ≥ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE; v5.0) (repeat testing is allowed once) at screening and Day -1
16. Presence of out-of-range cardiac interval (PR ≥120 msec, PR ≤220 msec, QRSD \<120 msec and QTcF ≤450 msec for males and females) on the ECG at screening and Day -1 or other clinically significant ECG abnormalities, unless deemed non significant by the Investigator
17. Presence of clinically significant vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 resp/min) at screening and Day -1.
18. Use of Δ9-tetrahydrocannabinol (THC)- or cannabidiol (CBD)-containing products within 60 days of start of study (Day 1)
19. Serious illness in the 30 days preceding the beginning of treatment on Day 1 (i.e., that resulted in hospitalization)
20. Receipt of treatment for any type of internal cancer within the 5 years prior to enrollment (fully treated and resolved basal cell carcinoma and or squamous cell carcinoma are permissible)
21. Females who are pregnant, plan to become pregnant during the study, or are breastfeeding a child
22. Positive alcohol breath test or urine drug screen at screening or at admissions on Day -1
23. Blood or plasma donation (500 mL) within the past month, or receipt of blood transfusion within 1 month prior to Day 1
24. Employee, family member, or student of the Investigator or clinical site(s)

Contraception:

Male participants who are not vasectomized for at least 6 months prior to dosing, and who are sexually active with a female partner of childbearing potential must be willing to use one of the following acceptable contraceptive methods from the first dose and for 90 days after the last dose:

* Simultaneous use of condom and established use of oral, injected or implanted hormonal contraceptive (at least 4 weeks prior to screening)
* Simultaneous use of condom and placement of intrauterine device (IUD) or intrauterine system (IUS)

There are no contraceptive requirements if any of following conditions apply:

* Sexual partner is surgically sterile;
* Partner of non-childbearing potential;
* Same sex relationship;
* Abstinence from heterosexual intercourse as usual and preferred lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.

Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomised at least 6 months prior to the first study drug administration) must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 3 months after the last study drug administration:

- Simultaneous use of intrauterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration; or intrauterine contraceptive device with hormone release system placed at least 12 weeks prior to first study drug administration; or oral hormonal contraceptives (minimum 12 week use without issue), and a condom for the male partner.

Females of non-childbearing potential must be:

* Post-menopausal (absence of menses for at least 12 months prior to the first study drug administration) with confirmation of the post menopausal status by documented FSH level ≥40 mIU/mL; or
* Surgically sterile (complete hysterectomy or bilateral oophorectomy at least 3 months prior to the first study drug administration).

Please note women with tubal ligation will be required to undergo a pregnancy tests and partner to use a condom (ie. they will be treated as WOCBP).

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 21 days
measure: Serious Adverse Events
timeFrame: Up to 21 days
measure: Adverse Events of Special Interest
timeFrame: Up to 21 days
measure: Changes from baseline in hematology
timeFrame: Up to 21 days
measure: Changes from baseline in serum chemistry
timeFrame: Up to 21 days
measure: Changes from baseline in urinalysis
timeFrame: Up to 21 days
measure: Changes from baseline in blood pressure
timeFrame: Up to 21 days
measure: Changes from baseline in heart rate
timeFrame: Up to 21 days
measure: Changes from baseline in respiratory rate
timeFrame: Up to 21 days
measure: Changes from baseline in body temperature
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of heart rate
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of PR interval
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of RR interval
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of QRS duration
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of QT interval
timeFrame: Up to 21 days
measure: Changes from baseline in ECG recording of QTcF
timeFrame: Up to 21 days
measure: Clinically significant physical examination findings
timeFrame: Up to 21 days
measure: Changes in suicidal ideation and behavior
timeFrame: Up to 21 days
measure: Use of concomitant medications
timeFrame: Up to 21 days
Secondary outcomes:
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Cmin
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Cmax
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Tmax
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: AUC0-last
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: AUC0-inf
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: lz
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: t1/2
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: Cl/F
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: Vz/F
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: CTlast
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: AUC0-tau
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: Vd/F,ss
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: Cl/F,ss
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: Aer
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: fe%
timeFrame: Up to 21 days
measure: Pharmacokinetics for primary cannabinoids and metabolites in Cohort B: CLr [Ae0-t/AUC0-t]
timeFrame: Up to 21 days
measure: Change from baseline in subjective pharmacodynamic effects
timeFrame: Up to 21 days
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Q-Pharm Pty Ltd
state: Queensland
Study officials:
affiliation: Q-Pharm Pty Ltd
name: Kristi McLendon, MD
role: PRINCIPAL_INVESTIGATOR
References: