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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001249347
Ethics application status
Help: Ethics application status
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
Help: Data sharing statement date
14/10/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PNV-8297 in Healthy Volunteers
Scientific title
A Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PNV-8297 in Healthy Volunteers
Additional trial identifiers [1] 318174 0
PNV-8297-001
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Major Depressive Disorder 343231 0
Depression 343783 0
Condition category
Condition code
Mental Health 339335 339335 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 A: Single Ascending Dose (SAD):
Healthy volunteers will be enrolled in one of 6 SAD cohorts with up to 8 participants per cohort. Safety and tolerability of each dose will be measured with new cohorts introduced in an ascending pattern as follows: 30 mg, 60 mg, 120 mg, 240 mg, 480 mg, 720 mg. Participants will receive a single dose of PNV-8297 (or placebo) on Day 1 of the study.

Dosing in each cohort will commence with 2 sentinel participants, whereby one of the two sentinel participants will be randomised to receive PNV-8297 and the other randomised to receive placebo. The safety and tolerability of each sentinel participant will be monitored in the clinic. The Principal Investigator (PI) will review safety/tolerability information available on the sentinel participants at 24 hours post-dose, prior to dosing the remainder of participants in each cohort.

If the dose is found to be safe and well tolerated, 6 more participants will be randomised to the cohort - 5 participants will receive PNV-8297 and one will receive placebo.

Part B: Multiple Ascending Doses (MAD):
Up to 24 healthy volunteers will be enrolled into one of three MAD cohorts. Each cohort will enrol up to 8 participants, 6 will receive PNV-8297 and 2 will receive placebo. The three active treatment doses will be determined based on safety data from the SAD cohorts, and participants will take one dose per day for 14 days (a total of 14 doses).

Participants of both the SAD and MAD groups will be confined to the study site for the duration of dosing, so adherence to the study treatment will be monitored by study staff.
Intervention code [1] 335072 0
Treatment: Drugs
Description of the comparator or control
The control treatment (placebo) will be an oral film-coated, immediate-release cellulose/lactose capsule that is visually identical to the study treatment, but it will not contain the active ingredient.

Participants in the SAD group will receive one dose of placebo on Day 1 of the study, and participants in the MAD group will receive one dose of placebo each day for 14 consecutive days, from Day 1 to Day 14 of the study.
Control group
Placebo

Outcomes
Primary outcome [1] 346548 0
Measure the incidence, severity, and relationship of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs; including withdrawals due to AEs), measured as a composite outcome.
Timepoint [1] 346548 0
AEs will be monitored continuously from baseline (Day -1) to end-of-study (Day 8, one week after receiving PNV-8297).
Primary outcome [2] 346549 0
Measure a change from baseline in vital signs measurements, body weight, 12 lead electrocardiogram (ECG), and clinical laboratory results (haematology, serum chemistry, coagulation, urinalysis) - measured as a composite outcome.
Timepoint [2] 346549 0
Vital signs will be collected at the following time points - Part A: 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 8); Part B: Baseline (Day -1), Pre-dose on Day 1, 1, 4, 24, 48, 72 and 96 hours post-dose, on Days 6-15, and at end-of-study visit (Day 21). Body weight will be measured at the following time points - Part A: Baseline (Day -1), and 72 hours post-dose; Part B: Baseline (Day -1) and on Day 15. ECG parameters will be collected at the following time points - Part A: Baseline (Day -1), Pre-dose on Day 1. 4 and 24 hours post-dose, and at end-of-study visit (Day 8); Part B: Baseline (Day -1), Pre-dose on Day 1, 4, 24 and 96 hours post-dose, on Day 15, and at end-of-study visit (Day 21). Clinical laboratory tests and urinalysis will be performed at the following time points - Part A: Baseline (Day -1) Pre-dose on Day 1, 6, 24 and 48 hours post-dose, and at end-of-study visit (Day 8); Part B: Baseline (Day -1), Pre-dose on Day 1, 6, 24 and 96 hours post-dose, on Day 15, and at end-of-study visit (Day 21).
Primary outcome [3] 346754 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] 346754 0
C-SSRS questionnaires will be completed at the following time points - Part A: Baseline (Day -1), 4 and 24 hours post-dose, and at end-of-study visit (Day 8); Part B: Baseline (Day -1), 4 and 24 hours post-dose, on Day 15, and at end-of-study visit (Day 21).
Secondary outcome [1] 467347 0
Part A: Measure how the body interacts with PNV-8297 as a single oral dose in healthy adult participants.
Timepoint [1] 467347 0
Part A: 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 8). Urine PK samples will be collected in Cohorts 3 and 5 only at the following time points: Pre-dose on Day 1, 0-4, 4-8, 8-24, 24-48 and 28-72 hours post-dose, and at end-of-study visit (Day 8).
Secondary outcome [2] 467348 0
Part B: Measure how the body interacts with PNV-8297 as multiple ascending doses in healthy adult participants.
Timepoint [2] 467348 0
Part B: 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, 72 and 96 hours post-dose, on Days 14-18, and at end-of-study visit (Day 21).

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)
All study participants who sign a participant informed consent form (PICF) will receive a unique sequential number (i.e., a screening number).

Participants who meet the study eligibility criteria will be assigned a randomisation number, which corresponds to a study treatment (PNV-8297 or placebo; Parts A and B) in accordance with the randomisation schedule.

As Parts A and B of the study are double-blinded, sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) and will be retained at the study site in a secure, accessible location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
For Parts A and B, the allocation to PNV-8297 or placebo will be performed using a block randomisation algorithm.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
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
26/10/2026
Actual
Date of last participant enrolment
Anticipated
9/07/2027
Actual
Date of last data collection
Anticipated
30/07/2027
Actual
Sample size
Target
72
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 322740 0
Commercial sector/Industry
Name [1] 322740 0
ProNovo Therapeutics Australia Pty Ltd
Country [1] 322740 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ProNovo Therapeutics Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 325843 0
None
Name [1] 325843 0
Address [1] 325843 0
Country [1] 325843 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321179 0
Bellberry Human Research Ethics Committee K
Ethics committee address [1] 321179 0
Ethics committee country [1] 321179 0
Australia
Date submitted for ethics approval [1] 321179 0
26/08/2026
Approval date [1] 321179 0
01/10/2026
Ethics approval number [1] 321179 0

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

Contacts
Principal investigator
Name 152926 0
Dr Xiu Lim
Address 152926 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 152926 0
Australia
Phone 152926 0
+61 0423 224 361
Fax 152926 0
Email 152926 0
[email protected]
Contact person for public queries
Name 152927 0
Xiu Lim
Address 152927 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 152927 0
Australia
Phone 152927 0
+61 0423 224 361
Fax 152927 0
Email 152927 0
[email protected]
Contact person for scientific queries
Name 152928 0
Xiu Lim
Address 152928 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 152928 0
Australia
Phone 152928 0
+61 0423 224 361
Fax 152928 0
Email 152928 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.