Pharmacokinetics and Safety of Single-Dose Wafermine™ (Ketamine Sublingual Wafer) in Healthy Subjects

NCT07691372 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KET004
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, three-period crossover study evaluating the pharmacokinetics and safety of single-dose Wafermine™ (ketamine sublingual wafer) at dose levels of 25 mg, 50 mg, and 75 mg in healthy adult participants under fasting conditions. Participants will receive all three dose levels in a fixed ascending sequence during a single inpatient admission, with washout periods between doses. Pharmacokinetic sampling will be conducted over 36 hours following each dose.

Conditions

Healthy Adult Participants

Keywords

Ketamine; Pharmacokinetics; Sublingual; Wafer; Phase 1; Healthy Volunteers; Wafermine

Outcome Measures

Primary Outcomes (4)

• Peak Plasma Concentration (Cmax) of Ketamine and Norketamine

  Maximum observed plasma concentration (Cmax) of ketamine and norketamine following administration of study treatment. Plasma concentrations will be derived using non-compartmental analysis (NCA).

  From pre-dose through the last measurable concentration, with plasma samples collected up to 36 hours post-dose.

• Terminal Elimination Half-Life (t½) of Ketamine and Norketamine

  Terminal elimination half-life (t½) of ketamine and norketamine calculated from the terminal phase of the plasma concentration-time curve using non-compartmental analysis.

  From pre-dose through the last measurable concentration, with plasma samples collected up to 36 hours post-dose.

• Time to Peak Plasma Concentration (Tmax) of Ketamine and Norketamine

  Time to maximum observed plasma concentration (Tmax) of ketamine and norketamine following administration of study treatment.

  Pre-dose to 36 hours post-dose

• Area Under the Plasma Concentration-Time Curve (AUC) of Ketamine and Norketamine

  Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC₀-t) and extrapolated to infinity (AUC∞) for ketamine and norketamine, calculated using non-compartmental analysis.

  From pre-dose through the last measurable concentration, with plasma samples collected up to 36 hours post-dose.

Secondary Outcomes (16)

• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)

  From first dose through end of study/follow-up (~10 days)

• Vital Signs: Change From Baseline in Systolic Blood Pressure

  From first dose through End of study/ follow-up, approximately 10 days

• Vital Signs: Change From Baseline in Diastolic Blood Pressure

  From first dose through end of study/ follow-up, approximately 10 days

• Vital Signs: Change from Baseline in Heart Rate

  From first dose through End of study/ follow-up, approximately 10 days

• Vital Signs: Change From Baseline in Respiratory Rate

  From first dose through end of study/follow-up, approximately 10 days

Study Arms (1)

Wafermine™ Sublingual Wafer

EXPERIMENTAL

Participants will receive single doses of Wafermine™ (25 mg, 50 mg and 75 mg) administered sublingually in three sequential treatment periods.

Drug: Wafermine™ (ketamine sublingual wafer)

Interventions

Wafermine™ (ketamine sublingual wafer) DRUG

Single-dose sublingual administration of Wafermine™ at dose levels of 25 mg, 50 mg, and 75 mg under fasting conditions.

Wafermine™ Sublingual Wafer

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically healthy participants (male and female) aged ≥ 18 to ≤ 65 years at the time of signing the informed consent.
• Research participants with no history of clinically significant cardiac, endocrine, gastrointestinal, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological, dermatological, or renal diseases or comorbidity of significance at the discretion of the Principal Investigator (or his/her delegate). The following medical history are permitted at the discretion of the Principal Investigator: history of childhood asthma; prior history of cholecystectomy; history of eczema with no use of steroid creams for 3 months prior to screening; history of fully resolved gestational diabetes; current or history of ADHD, anxiety or antidepression ( stable condition with no use of antidepressants 6 months prior to screening)
• Be able and willing to read, understand, sign, and date the Informed Consent Form prior to entering the study.
• Have adequate venous access for blood sampling.
• Female participants are eligible only if all the following contraceptive requirements are met:
• These requirements also apply to ova donation.
• Women of non-childbearing potential (WONCBP) are not required to use contraception and are defined as women who meet at least one of the following criteria:
• Have undergone surgical sterilisation (e.g., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or
• Are postmenopausal, defined as at least 12 consecutive months of amenorrhea without an alternative medical cause, with confirmation by follicle-stimulating hormone (FSH) levels at screening, where required.
• Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception, defined as methods with a failure rate of \<1% per year when used consistently and correctly, from screening until at least 33 days after the last administration of the investigational product.
• Acceptable highly effective methods of contraception include:
• Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal) associated with inhibition of ovulation
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)

You may not qualify if:

• Medical history
• Research participants with inflammatory or ulcerative disease in the oral cavity that may affect the absorption of the sublingual presentation.
• History of allergic reactions, anaphylactic reactions, severe systemic hypersensitivity, or any allergic reaction that, in the opinion of the Principal Investigator or his or her delegate, is likely to be exacerbated by the study drug.
• History of hypersensitivity to ketamine or any of the WafermineTM excipients.
• Elective procedures or surgeries scheduled after signing the Informed Consent Form and until the safety follow-up call \[3 days ± 1 day after the 36.0-hour third period is taken\].
• History of gastric bypass surgery/bariatric surgery or other gastrointestinal surgery or condition that may affect gastric emptying or absorption of the study drug.
• A history of 6 previous months of psychiatric disorders (schizophrenia, anxiety, acute psychosis, depression). A clinically significant history of psychiatric disorders (including but not limited to: schizophrenia, anxiety, acute psychosis, depression). Resolved psychiatric disorders (\>6 months before screening) may be included at the discretion of the Investigator or delegate).
• Risk of infection
• Positive serology for hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
• Presence of chronic, recurrent, or severe infection (e.g., pneumonia, sepsis) at the discretion of the Principal Investigator, within 90 days prior to the screening visit and between the screening visit and Day -1.
• Presence of symptoms of bacterial, fungal, or viral infection (including upper respiratory tract infection) within 14 days prior to the screening visit and between screening and Day -1. Participants with local fungal infection (e.g., candidiasis, ringworm, tinea pedis) are eligible for reevaluation after successful treatment of the infection.
• History of clinically significant condition involving the bladder or urinary tract, including frequent urinary tract infections (e.g. \> 2 per year), or current symptoms of bladder irritation such as frequent or urgent need to urinate or burning with urination.
• Any immunization or vaccine administered within 30 days prior to Day 1. Laboratory assessment and results
• Abnormal and clinically significant results at the discretion of the Principal investigator (or his/her delegate) in the laboratory tests and electrocardiogram of the screening visit. Laboratory values out of range and determined to be not clinically significant at the discretion of the Principal Investigator or his/her delegate may be repeated on one occasion, the subject may be enrolled if the repeated value is within the normal range.
• Participants with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin values ≥1.5 × upper limit of normal (ULN) at screening.

Sponsors & Collaborators

• iX Biopharma Ltd.: lead
• United States Department of Defense: collaborator

Study Sites (1)

Q-Pharm Pty Ltd.

Brisbane, Queensland, 4006, Australia

Location

Study Officials

• Janakan Krishnarajah, MD

  STUDY DIRECTOR

Central Study Contacts

Janakan Krishnarajah, MD

CONTACT

+61 412 999 004; j.krishnarajah@ixbiopharma.com

Janakan Krishnarajah, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive three single-dose treatments of Wafermine™ (25 mg, 50 mg, and 75 mg) in a fixed ascending sequence across three treatment periods during a single inpatient admission. Each treatment period is separated by a washout period of at least 48 hours.

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: July 8, 2026
• Study Start: June 9, 2026
• Primary Completion: July 17, 2026
• Study Completion: July 17, 2026
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Planned

Locations

AU (1)