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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001250325
Ethics application status
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Approved
Date submitted
Help: Date submitted
25/09/2026
Date registered
Help: Date registered
14/10/2026
Date last updated
Help: Date last updated
14/10/2026
Date data sharing statement initially provided
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14/10/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Effect of Food on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PNV-8297 in Healthy Volunteers
Scientific title
A Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Effect of Food on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PNV-8297 in Healthy Volunteers
Additional trial identifiers [1] 318357 0
PNV-8297-001
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Major Depressive Disorder 343496 0
Depression 343785 0
Condition category
Condition code
Mental Health 339592 339592 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
The study drug, PNV-8297, is a potent, highly selective negative allosteric modulator (NAM) of a5-GABAA receptors (a5-GABAARs). The study drug is formulated as a tablet for oral administration.

Part C: Food Effect (FE):
Active treatment sequence C1: Fasted-Fed (n=6) will act as the Intervention. The dose of PNV-8297 administered will be 120 mg.

The FE cohort is a randomised crossover design, whereby participants will receive a doses of PNV-8297 on Day 1 and 7 of the study, and they will be fed and fasted on different days. Sequence C1 (Intervention) will remain fasted on Day 1 and will eat a high-fat, high-calorie meal within 30 minutes prior to taking the study drug on Day 7.

The meal provided to participants will be approximately 800-1000 calories. 500-600 calories will be derived from fat, 150 calories from protein, and 250 calories from carbohydrates. An example of a standard meal is:
- Two eggs fried in butter
- Two strips of bacon
- Two slices of toast with 32 g butter
- 2 hash browns (approximately 115 g)
- 1 cup (approximately 250 mL) of full cream milk
Intervention code [1] 335248 0
Treatment: Drugs
Description of the comparator or control
The study drug, PNV-8297, is a potent, highly selective negative allosteric modulator (NAM) of a5-GABAA receptors (a5-GABAARs). The study drug is formulated as a tablet for oral administration.

Part C: Food Effect (FE):
Active treatment sequence C2: Fed-Fasted (n=6) will act as the Comparator. The dose of PNV-8297 administered will be 120 mg.

The FE cohort is a randomised crossover design, whereby participants will receive a doses of PNV-8297 on Day 1 and 7 of the study, and they will be fed and fasted on different days. Sequence C2 (Comparator) will eat a high-fat, high-calorie meal within 30 minutes prior to taking the study drug on Day 1, and will remain fasted on Day 7.

The meal provided to participants will be approximately 800-1000 calories. 500-600 calories will be derived from fat, 150 calories from protein, and 250 calories from carbohydrates. An example of a standard meal is:
- Two eggs fried in butter
- Two strips of bacon
- Two slices of toast with 32 g butter
- 2 hash browns (approximately 115 g)
- 1 cup (approximately 250 mL) of full cream milk
Control group
Active

Outcomes
Primary outcome [1] 346766 0
Measure the incidence, severity, and relationship of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs; including withdrawals due to AEs) in healthy adult volunteers who receive a single oral dose of PNV-8297 in a fasted and fed state, measured as a composite outcome.
Timepoint [1] 346766 0
AEs will be monitored continuously from baseline (Day -1) to end-of-treatment (Day 14, two weeks after the initial dose and one week after the second dose of PNV-8297).
Primary outcome [2] 346769 0
Measure a change from baseline in vital signs measurements, body weight, 12 lead electrocardiogram (ECG), and clinical laboratory results (haematology, serum chemistry, coagulation) - measured as a composite outcome.
Timepoint [2] 346769 0
Vital signs will be collected at the following time points - Baseline (Day -1), Pre-dose on Day 1, 0.25, 1, 4, 8, 12 and 24 hours post-dose, and at end-of-study visit (Day 14). Body weight will be measured at the following time points - Baseline (Day -1), and 72 hours post-dose. ECG parameters will be collected at the following time points - Baseline (Day -1), Pre-dose on Day 1. 4 and 24 hours post-dose, and at end-of-study visit (Day 14). Clinical laboratory tests will be performed at the following time points - Baseline (Day -1) Pre-dose on Day 1, 6, 24 and 48 hours post-dose, and at end-of-study visit (Day 14).
Primary outcome [3] 346770 0
Measure changes in the occurrence, severity and frequency of suicidal thoughts in participants who receive PNV-8297, measured as a composite outcome.
Timepoint [3] 346770 0
C-SSRS questionnaires will be completed at the following time points: Baseline (Day -1), 4 and 24 hours post-dose, and at end-of-study visit (Day 14).
Secondary outcome [1] 467435 0
Measure how the body interacts with PNV-8297 when administered with or without a high-calorie meal in healthy adult participants, measured as a composite outcome.
Timepoint [1] 467435 0
PK blood samples will be collected at the following time points: Pre-dose on Day 1, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose, and at end-of-study visit (Day 14).

Eligibility
Key inclusion criteria
* Adult males and females, 18 to 65 years of age (inclusive) at Screening.
* Body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive) at Screening.
* Medically healthy (in the opinion of the PI or delegate), as determined by pre-study medical history, and without clinically significant (CS) abnormalities.
* Female volunteers must be of non-childbearing potential or be willing to avoid pregnancy by using adequate contraception.
* Male volunteers must agree not to donate sperm and to use adequate contraception with female partners.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
Yes
Key exclusion criteria
* Known hypersensitivity to the study drug or any of the study drug ingredients, or history of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
* History or presence of CS cardiovascular, pulmonary (participants with resolved childhood asthma may be included), hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, or dermatologic disease/disorder, including any acute illness, within the past 3 months prior to Screening,
* History or presence of any mental health disorders or significant psychiatric illness (including but not limited to Major Depressive Disorder (MDD), bipolar disorder, schizophrenia spectrum disorder, psychotic disorder, personality disorder, or other major psychiatric disorder) that required hospitalisation or resulted in significant functional impairment, or use of any psychotropic medication (including but not limited to antidepressants, antipsychotics, anxiolytics, mood stabilisers, or stimulants) within the past 12 months prior to Screening,
* History or presence of panic attacks, severe insomnia, anxiety disorder, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), or eating disorder within the past 12 months prior to Screening.
* History, presence, or risk of suicidal ideation, behaviour, or self-harm within the past 12 months prior to Screening.
* History or presence of CS neurological abnormalities including (but not limited to) known structural or congenital neurological abnormalities, acute neurological events, history or current experience of migraines, abnormal electroencephalogram (EEG) at Screening.
* History or presence of syncope of unexplained origin or epilepsy, or family history of epilepsy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants who meet the study eligibility criteria will be assigned a randomisation number prior to dosing on Day 1, which corresponds to a treatment sequence (treatment sequence C1 fasted/fed or treatment sequence C2 fed/fasted). Randomisation numbers assigned will be in accordance with the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to treatment sequence C1 or C2 will be performed using a block randomisation algorithm. The randomisation schedule will be prepared by the statistician(s).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Sequential.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2026
Actual
Date of last participant enrolment
Anticipated
9/07/2027
Actual
Date of last data collection
Anticipated
30/07/2027
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 322917 0
Commercial sector/Industry
Name [1] 322917 0
ProNovo Therapeutics Australia Pty Ltd
Country [1] 322917 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ProNovo Therapeutics Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 325845 0
None
Name [1] 325845 0
Address [1] 325845 0
Country [1] 325845 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321343 0
Bellberry Human Research Ethics Committee K
Ethics committee address [1] 321343 0
Ethics committee country [1] 321343 0
Australia
Date submitted for ethics approval [1] 321343 0
26/08/2026
Approval date [1] 321343 0
01/10/2026
Ethics approval number [1] 321343 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 153430 0
Dr Xiu Lim
Address 153430 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 153430 0
Australia
Phone 153430 0
+61 0423 224 361
Fax 153430 0
Email 153430 0
[email protected]
Contact person for public queries
Name 153431 0
Xiu Lim
Address 153431 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 153431 0
Australia
Phone 153431 0
+61 0423 224 361
Fax 153431 0
Email 153431 0
[email protected]
Contact person for scientific queries
Name 153432 0
Xiu Lim
Address 153432 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 153432 0
Australia
Phone 153432 0
+61 0423 224 361
Fax 153432 0
Email 153432 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.