Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001308583p
Ethics application status
Submitted, not yet approved
Date submitted
9/10/2024
Date registered
29/10/2024
Date last updated
29/10/2024
Date data sharing statement initially provided
29/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A study comparing two formulations of R-107 under fasting conditions
Scientific title
A single dose, randomized, two period, two sequence, crossover, relative bioavailability study comparing R-107-H with R-107-P in healthy participants under fasting conditions.
Secondary ID [1] 313047 0
None
Universal Trial Number (UTN)
U1111-1312-5368
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 335271 0
Condition category
Condition code
Mental Health 331844 331844 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulation of 3 x 60 mg R-107-H extended release (ER) tablets on one occasion.

The intervention for this trial is the test R-107-H formulation. The active ingredient in R-107-H is ketamine.

The duration of the study is approximately 6 weeks;
- Up to 3 weeks for screening;
- Two study periods each occurring over 3 days with dose administration on day 1 and clinical procedures and PK sample collection during each 3 day study period;
- Minimum of 1-week washout period between each dose administration period and 1 day for study exit procedures.

The intervention formulation will be administered as a single dose on one occasion only i.e. 3 x 60 mg R-107-H tablets taken on Study Day 1, and will be taken orally with 240 ml of water at ambient temperature. The tablets will be swallowed whole and a mouth check will be conducted to ensure the medication has been taken as directed.
Intervention code [1] 329602 0
Treatment: Drugs
Comparator / control treatment
The comparator/control for this trial is the innovator R-107-P extended release formulation. The active ingredient in R-107-P is ketamine.
Control group
Active

Outcomes
Primary outcome [1] 339482 0
To compare bioavailability, as summarised by AUC0-t and Cmax following the administration of 3 × 60 mg (180 mg) R-107-H extended release (ER) tablets, relative to administration of 3 × 60 mg (180 mg) R-107-P extended release (ER) tablets.
Timepoint [1] 339482 0
Pre-dose (0 hours) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 12, 18, 24, 32 and 48 hours after dose administration in each study period to determine AUC and Cmax.
Secondary outcome [1] 440426 0
To determine the pharmacokinetics of ketamine and norketamine in urine
Timepoint [1] 440426 0
Urine collection sample window times: -1 to 0 (pre-dose), 0-1, 1-2, 2 4, 4-6, 6-8, 8-12, 12-16, 16-24, 24-32, 32-48 hours after dose administration.
Secondary outcome [2] 440427 0
To assess the single-dose safety and tolerability of the formulations. This will be assessed as a c composite outcome.
Timepoint [2] 440427 0
Adverse events will be reported from the time a signed and dated Consent Form (CF) is obtained until completion of the participant's last study-related procedure (which may include contact for follow-up of safety). On each study day at each sampling timepoint throughout the study participants will be asked how they feel and if they are experiencing any adverse events. Adverse event assessment will be completed and review will take place in real time with a further review occurring at the end of each study period for any adverse events requiring further follow up.

Vital signs at pre-dose and at 0.5, 1, 2, 3, 4, 6, 12, 24, 32 and 48 hours after dose administration.

Columbia Suicide Severity rating scale (C-SSRS) at screening, pre-dose (Time 0) and 24 hours post-dose

BPRS+, CADSS and MOAA/S assessments performed pre-dose (Time 0), and at 30 minutes, 1 hour, 2 hours and 4 hours post-dose.

Electrocardiograms (ECGs) pre-dose and at 2 and 4 hours after dose administration in each study period. ECGs may be repeated to confirm abnormal readings.

Eligibility
Key inclusion criteria
Healthy males and non-pregnant female volunteers.
Aged between 18 and 55 on day of consent
Non-smoker
Drug free as determined by a Urine Drugs Test
BMI between 18.5 and 33.0
Normal, healthy individuals as determined by medical history, physical examination, ECG, vital signs and laboratory tests
Able to provide written informed consent in English
Able to adhere to all study restrictions and attend all study visits
Consent to GP being contacted if necessary
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Known history or presence of any clinically significant medical conditions
Any clinically significant abnormality at physical examination or clinically significant abnormal laboratory test results as determined by the Investigator.
Positive test result for hepatitis B, hepatitis C, or HIV
A known allergy, hypersensitivity, or intolerance to ketamine, or other forms of ketamine, or its excipients.
History of significant alcohol abuse within one year prior to date of consent or regular use of alcohol within six months prior to the date of consent
History of significant drug abuse or dependency including ketamine or its excipients within one year prior to date of consent.
Use of Class A, B and C drugs as classified in the Misuse of Drugs Act 1975 within 3 months prior to the date of consent.
Significant current risk of suicide:
o As assessed by C-SSRS, or
o as assessed by the evaluating Trial Physician
Participation in a clinical research study within 60 days prior to Study Day 1
Use of medication other than topical products without significant systemic absorption.
Receiving treatment with monoamine oxidase inhibitors, vasoconstriction agents, thyroxine or benzodiazepines;
Prescription medication (except prescribed hormonal contraceptive) within 14 days prior to Study Day 1;
Over-the-counter products and natural health products within 7 days prior to Study Day 1, with the exception of the occasional use of paracetamol (up to 2 g daily);
Use of any enzyme-modifying drugs and/or other products in the previous 30 days before first study drug administration
Donation of platelets or plasma within 30 days prior to Study Day 1.
Participants of child-bearing potential who are pregnant, lactating or breastfeeding.
Participants of childbearing potential who are sexually active and are not using effective contraception for the prevention of pregnancy (i.e. prescribed hormonal contraceptives or other reliable method)
An employee or first-degree family member of an employee of the Sponsor or the Contract Research Organisation (CRO).
Unable to swallow tablets
Participants who have poor venous access or cannot tolerate venepuncture, IV cannula insertion or who have a fear of needles or blood
Any participant for whom the Investigator believes, for any reason, inclusion would not be an acceptable risk.
Consumption of grapefruit, grapefruit juice, or Seville oranges for 72 hours before the first dose of IP administration on Day 1.
Any clinically significant illness in the 30 days prior to Study Day 1.

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 formulations will be labelled as Formulation A and B. The identification of each treatment will only be known to the Managing Director and the Section Head - Trails and Regulatory Affairs or their delegates.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each participant will be given a 3 digit screening number and a 2 digit subject number. The screening number will be issued once the participant has given written consent to participate in the study and the two digit subject number (randomisation number) after acceptance into the study. Sequence generation will be by using a simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
34
Accrual to date
Final
Recruitment outside Australia
Country [1] 26580 0
New Zealand
State/province [1] 26580 0
Otago

Funding & Sponsors
Funding source category [1] 317488 0
Commercial sector/Industry
Name [1] 317488 0
Douglas Pharmaceuticals Limited
Country [1] 317488 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
Country
New Zealand
Secondary sponsor category [1] 319780 0
None
Name [1] 319780 0
Address [1] 319780 0
Country [1] 319780 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316201 0
Northern B Health and Disability Ethics Committee 
Ethics committee address [1] 316201 0
Ethics committee country [1] 316201 0
New Zealand
Date submitted for ethics approval [1] 316201 0
12/09/2024
Approval date [1] 316201 0
Ethics approval number [1] 316201 0
2024 FULL 21349

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

Contacts
Principal investigator
Name 137122 0
Dr Noelyn Hung
Address 137122 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 137122 0
New Zealand
Phone 137122 0
+64 21 48 21 48
Fax 137122 0
Email 137122 0
[email protected]
Contact person for public queries
Name 137123 0
Ms Linda Folland
Address 137123 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 137123 0
New Zealand
Phone 137123 0
+64 3 477 9669
Fax 137123 0
Email 137123 0
[email protected]
Contact person for scientific queries
Name 137124 0
Tak Hung
Address 137124 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 137124 0
New Zealand
Phone 137124 0
+64 3 477 9669
Fax 137124 0
Email 137124 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.