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Trial registered on ANZCTR


Registration number
ACTRN12620000226909
Ethics application status
Approved
Date submitted
10/02/2020
Date registered
24/02/2020
Date last updated
24/02/2020
Date data sharing statement initially provided
24/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Study in healthy volunteers of the safety and how the body handles PCN-101
Scientific title
A Phase I Randomized, Placebo Controlled, Double-Blind, Single-Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PCN-101 (Arketamine) and a Relative Safety Comparison of PCN-101 and Esketamine in Healthy Volunteers
Secondary ID [1] 300068 0
PCN-101-02
Universal Trial Number (UTN)
U1111-1241-1005
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 315590 0
Condition category
Condition code
Mental Health 313878 313878 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in 2 parts.
Part 1 is a randomised, placebo-controlled, double-blind, safety and tolerability study of single ascending doses of PCN-101 administered via intravenous (IV) infusions over 40 minutes to healthy volunteers. A total of up to 48 healthy volunteers will be enrolled in Part 1. The study will evaluate safety, tolerability and pharmacokinetics (PK) of PCN-101. The starting dose is 5mg (cohort 1) and this will be escalated in each subsequent cohort (15mg, 30mg, 60mg, 100mg and 150mg)

Part 2 is a double-blind, crossover relative safety and tolerability study comparing a single dose of PCN-101 to esketamine. A total of 10 healthy volunteers will be randomised into one of 2 treatment groups. Treatment Group 1 will receive a single IV infusion over 40 minutes of PCN-101, then 48-hours later will receive a second IV infusion of esketamine. In Treatment Group 2, the order of infusions will be reversed. Part 2 will use the identified dose from Part 1 for PCN-101 and 15mg esketamine .

The cohorts are mutually exclusive.


Intervention code [1] 316356 0
Treatment: Drugs
Comparator / control treatment
Part 1 : Placebo, 0.9% normal saline

Part 2 : Esketamine 15mg
Control group
Placebo

Outcomes
Primary outcome [1] 322290 0
To assess the safety and tolerability of PCN-101 administered intravenously in human volunteers.
Timepoint [1] 322290 0
Safety and tolerability of PCN-101 will be evaluated by clinical laboratory assessments, physical examinations, weight, vital signs , 12- lead electrocardiogram (ECG), neuropsycholgical questionnaires and adverse events at screening, day 1, day 2 , and day 9.
Secondary outcome [1] 377984 0
To assess the PK of IV PCN-101 and its metabolites in plasma and urine.
Timepoint [1] 377984 0
Plasma PK parameters for PCN-101 and its metabolites include the following: Tmax, Cmax, AUC0-t, AUC0-8, Lambda z, t½, CL, Vz.

Urine PK parameters for PCN-101 and its metabolites include the following: Ae, fe, and CLr.

PK sampling times are measured from the start of infusion. Blood will be drawn from subjects for PK analysis at the following sampling times: Predose , 5 min , 10 min, 15 min, 30 min, 40 minutes, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 8 hr, 12 hr, 24 hr post-dose.

Urine samples for PK assessments of PCN-101 and its metabolites will be collected as single collection at predose and for pooled intervals of 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours after dosing.
Secondary outcome [2] 377985 0
To explore the dose proportionality of PCN-101 and its metabolites, if applicable
Timepoint [2] 377985 0
Assessment of dose proportionality will be conducted utilising Cmax and AUC Blood will be drawn at the following sampling times: Predose, 5 min, 10 min, 15 min, 30 min, 40 minutes, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 8 hr, 12 hr, 24 hr post-dose
Secondary outcome [3] 377988 0
To compare the relative safety profile of PCN-101 and esketamine.
Timepoint [3] 377988 0
Safety will be evaluated by clinical laboratory assessments, physical examinations, weight, vital signs, 12- lead electrocardiogram (ECG), neuropsychological questionnaires, sedation and adverse events at screening, day 1, day 2, and day 9.
Secondary outcome [4] 380334 0
Plasma PK parameters for PCN-101
Timepoint [4] 380334 0
PCN -101 Plasma PK parameters for metabolites (norketamine, 6hydroxynorketamine, and dehydronorketamine) include the following: Tmax, Cmax, AUC0t, AUC0-8, Lambda z, t½, CL (PCN-101 only), Vz (PCN-101 only), and metabolite to parent ratios
Secondary outcome [5] 380335 0
Urine PK parameters for PCN-101
Timepoint [5] 380335 0
PCN-101 Urine PK parameters for metabolites include the following: Ae, fe, and CLr.

Eligibility
Key inclusion criteria
Inclusion Criteria:

• Able and willing to provide signed and dated informed consent
• BMI within the range of 18 to 30, weighing between 50 kg and 100 kg
• Healthy as determined by medical history, physical examination, and clinical laboratory evaluations
• Male subjects must be sterile for at least 6 months or agree to use a double barrier method of contraception
• Female subjects of child-bearing potential must be practicing a highly effective birth control
• Female subjects of non-childbearing potential must be either surgically sterile or post-menopausal
• Has a haemoglobin value of > 120 g/L at Screening
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria:
•Pregnant or breast-feeding female
• Has a primary diagnosis of current (active) generalised anxiety disorder, panic disorder, obsessive compulsive disorder, post traumatic stress disorder, anorexia nervosa, or bulimia nervosa
• Has an active psychotic disorder within 10 years of Baseline
• Is taking compound(s) known to induce or inhibit cytochrome P450 oxidase (CYP) drug metabolising enzymes
• Has clinically significant abnormalities in any of the clinical laboratory evaluations at Screening or Baseline
• Has hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg) or any history of a hypertensive crisis
• Has an abnormal ECG of clinical relevance at Screening or Baseline
• Has past history of seizures
• Has received an investigational drug or participated in a clinical trial within 30 days of Screening
• Has a drug or alcohol abuse disorder within the past 5 years prior to Baseline or there is reason to believe a subject has such a history
• Has smoked tobacco, used tobacco or nicotine products (including e-cigarettes) in the past 6 months prior to Baseline


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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
This would be a sequential (cohort following after completion of previous cohort). Part 1 is parallel per cohort only (PCN-101:placebo).
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22221 0
New Zealand
State/province [1] 22221 0
Auckland

Funding & Sponsors
Funding source category [1] 304517 0
Commercial sector/Industry
Name [1] 304517 0
PERCEPTION NEUROSCIENCE, INC.
Address [1] 304517 0
180 VARICK STREET, FLOOR 6, NEW YORK. NY10014
Country [1] 304517 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
PERCEPTION NEUROSCIENCE, INC.
Address
180 VARICK STREET, FLOOR 6, NEW YORK. NY10014
Country
United States of America
Secondary sponsor category [1] 304786 0
None
Name [1] 304786 0
Address [1] 304786 0
Country [1] 304786 0
Other collaborator category [1] 281136 0
Commercial sector/Industry
Name [1] 281136 0
Novotech (Australia) Pty Limited
Address [1] 281136 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 281136 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304948 0
Health and Disability Ethics Committees, Ministry of Health
Ethics committee address [1] 304948 0
133 Molesworth Street, PO Box 5013 Wellington, 6011
Ethics committee country [1] 304948 0
New Zealand
Date submitted for ethics approval [1] 304948 0
24/10/2019
Approval date [1] 304948 0
19/11/2019
Ethics approval number [1] 304948 0

Summary
Brief summary
This study in healthy volunteers aims to identify safe single doses of PCN-101 administered IV; to assess how the body handles IV PCN-101; and to compare the safety of PCN-101 and esketamine. The study aims to identify tolerable dosing of IV PCN-101 to be evaluated in future clinical trials. Part 1 of the study is an ascending dose, double-blind safety and tolerability study of single doses of IV PCN-101. Up to 48 healthy volunteers will be enrolled to receive a single dose of PCN-101 or placebo, as an infusion over 40 minutes. Part 2 is a double-blind, cross-over safety and tolerability study comparing a single dose of PCN-101 versus esketamine, both given IV over 40 minutes. Ten healthy volunteers will be randomized into one of two treatment groups. Group 1 will receive a single infusion of PCN-101 and then an infusion of esketamine. In Group 2, the order of infusions will be reversed. Safety will be assessed via vital signs, 12-lead ECG, clinical laboratory tests, neuropsychological scales, sedation and adverse events.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98734 0
Dr Christian Schwabe
Address 98734 0
Auckland Clinical Studies Ltd, 3 Ferncroft Street, Grafton, Auckland, 1010
Country 98734 0
New Zealand
Phone 98734 0
+64 93733474
Fax 98734 0
Email 98734 0
Christian.Schwabe@clinicalstudies.co.nz
Contact person for public queries
Name 98735 0
Dr Chief Medical Officer
Address 98735 0
PERCEPTION NEUROSCIENCE, INC.
180 VARICK STREET, FLOOR 6, NEW YORK. NY10014
Country 98735 0
United States of America
Phone 98735 0
+16469053973
Fax 98735 0
Email 98735 0
clinicaltrials@perceptionneuroscience.com
Contact person for scientific queries
Name 98736 0
Dr Chief Medical Officer
Address 98736 0
PERCEPTION NEUROSCIENCE, INC.
180 VARICK STREET, FLOOR 6, NEW YORK. NY10014
Country 98736 0
United States of America
Phone 98736 0
+16469053973
Fax 98736 0
Email 98736 0
clinicaltrials@perceptionneuroscience.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
None
What supporting documents are/will be available?
No other documents available
Summary results
No Results