A SAD, MAD and Food Effect Study to Evaluate the Safety, Tolerability, PK, and PD of AJA001 in Healthy Subjects

NCT06019065 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AJA001-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (19)

• Adverse Events

  Incidence, severity and relationship of Adverse events (AEs)

  Up to 21 days

• Serious Adverse Events

  Incidence of Serious adverse events (SAEs)

  Up to 21 days

• Adverse Events of Special Interest

  Incidence of AEs of special interest (AESI), including abnormal clinically significant liver function test values (aspartate aminotransferase, alanine aminotransferase, total bilirubin and estimated glomerular filtration rate) due to major active pharmaceutical ingredient

  Up to 21 days

• Changes from baseline in hematology

  Number of participants with changes from baseline in hematocrit, hemoglobin, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, platelet count, red blood cell count, reticulocyte count, white blood cell count, and differential white blood cell count

  Up to 21 days

• Changes from baseline in serum chemistry

  Number of participants with changes from baseline in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, sodium, potassium, chloride, calcium, magnesium, phosphorus, glucose, serum urea, uric acid, total bilirubin, creatinine, total protein, albumin, total cholesterol, triglycerides, creatinine phosphokinase, and follicle-stimulating hormone

  Up to 21 days

• Changes from baseline in urinalysis

  Number of participants with changes from baseline in microscopic examination, specific gravity, pH, protein, glucose, ketones, blood, urobilinogen, bilirubin, nitrites, leucocytes, immunoassay for THC

  Up to 21 days

• Changes from baseline in blood pressure

  Number of participants with changes from baseline in systolic and diastolic blood pressure in mm Hg

  Up to 21 days

• Changes from baseline in heart rate

  Number of participants with changes from baseline in pulse rate (beats/minute)

  Up to 21 days

• Changes from baseline in respiratory rate

  Number of participants with changes from baseline in respiratory rate (breaths/minute)

  Up to 21 days

• Changes from baseline in body temperature

  Number of participants with changes from baseline in body temperature (tympanic; °C)

  Up to 21 days

• Changes from baseline in ECG recording of heart rate

  Number of participants with changes in 12-lead electrocardiogram (ECG) recordings of heart rate in beats/minute

  Up to 21 days

• Changes from baseline in ECG recording of PR interval

  Number of participants with changes in 12-lead electrocardiogram (ECG) recordings of PR interval in msec

  Up to 21 days

• Changes from baseline in ECG recording of RR interval

  Number of participants with changes in 12-lead electrocardiogram (ECG) recordings of RR interval in msec

  Up to 21 days

• Changes from baseline in ECG recording of QRS duration

  Number of participants with changes in 12-lead electrocardiogram (ECG) recordings of QRS duration in msec

  Up to 21 days

• Changes from baseline in ECG recording of QT interval

  12-lead electrocardiogram (ECG) recordings of QT interval in msec

  Up to 21 days

• Changes from baseline in ECG recording of QTcF

  Number of participants with changes in 12-lead electrocardiogram (ECG) recordings of QTcF in msec

  Up to 21 days

• Clinically significant physical examination findings

  Number of participants with changes in the following parameters assessed during physical exams: general appearance, head, ears, eyes, nose, throat, neck (including thyroid), skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes and nervous system

  Up to 21 days

• Changes in suicidal ideation and behavior

  Number of participants with changes in Columbia Suicide Severity Rating Scale evaluation of suicidal ideation (yes/no), intensity of ideation (1-5 with 1 being the least severe and 5 being the most severe), and suicidal behavior (yes/no; if yes, include the number of attempts)

  Up to 21 days

• Use of concomitant medications

  All medications taken after the first dose of the study drug and through the EOS visit will be considered a concomitant medication

  Up to 21 days

Secondary Outcomes (17)

• Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Cmin

  Up to 21 days

• Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Cmax

  Up to 21 days

• Pharmacokinetics for primary cannabinoids and metabolites in Cohorts A and B: Tmax

  Up to 21 days

• Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: AUC0-last

  Up to 21 days

• Pharmacokinetics for primary cannabinoids and metabolites in Cohort A: AUC0-inf

  Up to 21 days

Study Arms (16)

Cohort A1: Single ascending dose of AJA001

EXPERIMENTAL

AJA001 active q.d. 2.2 mL oral dose level 1

Drug: AJA001

Cohort A1: Single ascending dose of placebo

PLACEBO COMPARATOR

AJA001 placebo q.d. 2.2 mL oral dose level 1

Other: Placebo

Cohort A2: Single ascending dose of AJA001

EXPERIMENTAL

AJA001 active q.d. ascending oral dose level 2

Drug: AJA001

Cohort A2: Single ascending dose of placebo

PLACEBO COMPARATOR

AJA001 placebo q.d. ascending oral dose level 2

Other: Placebo

Cohort A3: Single ascending dose of AJA001

EXPERIMENTAL

AJA001 active q.d. ascending oral dose level 3

Drug: AJA001

Cohort A3: Single ascending dose of placebo

PLACEBO COMPARATOR

AJA001 placebo q.d. ascending oral dose level 3

Other: Placebo

Cohort A4: Single ascending dose of AJA001

EXPERIMENTAL

AJA001 active q.d. ascending oral dose level 4

Drug: AJA001

Cohort A4: Single ascending dose of placebo

PLACEBO COMPARATOR

AJA001 placebo q.d. ascending oral dose level 4

Other: Placebo

Cohort B1: Multiple ascending doses of AJA001

EXPERIMENTAL

AJA001 active b.i.d. oral dose level 1

Drug: AJA001

Cohort B1: Multiple ascending doses of placebo

PLACEBO COMPARATOR

AJA001 placebo b.i.d. oral dose level 1

Other: Placebo

Cohort B2: Multiple ascending doses of AJA001

EXPERIMENTAL

AJA001 active b.i.d. oral dose level 2

Drug: AJA001

Cohort B2: Multiple ascending doses of placebo

PLACEBO COMPARATOR

AJA001 placebo b.i.d. oral dose level 2

Other: Placebo

Cohort B3: Multiple ascending doses of AJA001

EXPERIMENTAL

AJA001 active b.i.d. oral dose level 3

Drug: AJA001

Cohort B3: Multiple ascending doses of placebo

PLACEBO COMPARATOR

AJA001 placebo b.i.d. oral dose level 3

Other: Placebo

Cohort B4: Multiple ascending doses of AJA001

EXPERIMENTAL

AJA001 active b.i.d. oral dose level 4

Drug: AJA001

Cohort B4: Multiple ascending doses of placebo

PLACEBO COMPARATOR

AJA001 placebo b.i.d. oral dose level 4

Other: Placebo

Interventions

AJA001 DRUG

AJA001

Cohort A1: Single ascending dose of AJA001; Cohort A2: Single ascending dose of AJA001; Cohort A3: Single ascending dose of AJA001; Cohort A4: Single ascending dose of AJA001; Cohort B1: Multiple ascending doses of AJA001; Cohort B2: Multiple ascending doses of AJA001; Cohort B3: Multiple ascending doses of AJA001; Cohort B4: Multiple ascending doses of AJA001

Placebo OTHER

Placebo

Cohort A1: Single ascending dose of placebo; Cohort A2: Single ascending dose of placebo; Cohort A3: Single ascending dose of placebo; Cohort A4: Single ascending dose of placebo; Cohort B1: Multiple ascending doses of placebo; Cohort B2: Multiple ascending doses of placebo; Cohort B3: Multiple ascending doses of placebo; Cohort B4: Multiple ascending doses of placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• No known allergic reaction to cannabis products and formulation components (Glyceryl Monolinoleate, NF and organic chocolate mint flavoring agent)
• 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
• 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
• 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
• 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
• Refrain from donating sperm for the duration of the study and for at least 90 days after the last dose of investigational product (IP)
• Females must have a negative serum pregnancy test (SPT) at screening and urinary pregnancy test (UPT) at check-in on Day -1
• Agree to frequent blood sampling during the course of the study and with adequate venous access
• Agree to be confined for parts of the study in the Phase 1 unit and follow study procedures
• 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
• 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
• Able to read, understand, provide signed informed consent, communicate adequately, and comply with the requirements for the entire study.

You may not qualify if:

• 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.
• 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
• 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)
• Hypersensitivity or any significant allergic reaction to the investigational compound/compound class being used in this study or any ingredients of this medication
• 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;
• Personal diagnosis or first-degree relative diagnosis of psychosis/schizophrenia
• Presence of current psychiatric condition, suicide ideations or psychiatric condition requiring pharmacological management within the last 6 months
• 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)
• 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
• 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.
• 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%).
• History of or risk for seizures (one-off febrile seizure as a child is permissible)
• 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
• 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

Sponsors & Collaborators

• AJNA Australia Pty Ltd: lead

Study Sites (1)

Q-Pharm Pty Ltd

Brisbane, Queensland, 4006, Australia

Location

Study Officials

• Kristi McLendon, MD

  Q-Pharm Pty Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2023
• First Posted: August 31, 2023
• Study Start: September 13, 2023
• Primary Completion: March 26, 2024
• Study Completion: May 15, 2024
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)