Trial Review

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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
8/04/2021
Date data sharing statement initially provided
24/02/2020
Date results information initially provided
8/04/2021
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
Sex
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
Completed
Date of first participant enrolment
Anticipated
3/03/2020
Actual
25/02/2020
Date of last participant enrolment
Anticipated
2/06/2020
Actual
29/07/2020
Date of last data collection
Anticipated
19/06/2020
Actual
8/08/2020
Sample size
Target
58
Accrual to date
Final
58
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.
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 Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInvestigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.2022https://dx.doi.org/10.3389/fphar.2022.884155
N.B. These documents automatically identified may not have been verified by the study sponsor.