Clinical TrialTreatment-Resistant Depression (TRD)KetamineKetaminePlaceboCompleted

A multicentre, double-blind, randomised, placebo-controlled phase II trial with a 3 week treatment period to assess the efficacy, safety and tolerability of add-on treatment with Ketamine hydrochloride prolonged release tablets (KET01, 120 mg or 240 mg once daily) in outpatients with treatment resistant depression

Randomised, double-blind, placebo-controlled Phase II trial (n=180 planned) assessing once-daily KET01 prolonged-release ketamine tablets (120 mg or 240 mg) versus placebo as add-on therapy in outpatients with treatment-resistant depression.

Target Enrollment
180 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Multicentre, double-blind, randomised parallel-group Phase II trial evaluating the efficacy and safety of KET01 120 mg or 240 mg once daily versus matched placebo as add-on treatment for subjects with treatment-resistant major depressive disorder.

Primary outcome is change in MADRS total score from baseline to end of treatment; secondary outcomes include response/remission rates, HAM-D17, CGI-S, quality of life measures, sleep indices, dissociation (CADSS), vital signs and population pharmacokinetics of ketamine and metabolites.

Study Arms & Interventions

KET01 120 mg

experimental

KET01 prolonged-release tablet 120 mg once daily as add-on to standard antidepressant therapy for 3 weeks.

Interventions

  • Ketamine120 mg
    via Oral• once daily• 21 doses total

    120 mg KET01 OD for 3 weeks

KET01 240 mg

experimental

KET01 prolonged-release tablet 240 mg once daily as add-on to standard antidepressant therapy for 3 weeks.

Interventions

  • Ketamine240 mg
    via Oral• once daily• 21 doses total

    240 mg KET01 OD for 3 weeks

Placebo

inactive

Prolonged-release matching placebo tablet once daily for 3 weeks.

Interventions

  • Placebo
    via Oral• once daily• 21 doses total

    Matching prolonged-release placebo OD for 3 weeks

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Able to comprehend and willing to sign informed consent and comply with trial procedures.
  • Age ≥18 and ≤65 years.
  • BMI ≥18 and ≤35 kg/m2.
  • Primary diagnosis of major depressive disorder (DSM-5) with current episode ≤24 months confirmed by MINI 7.0.2.
  • Treatment-resistant depression (less than 50% improvement on ≥2 different optimised antidepressant treatments each ≥6 weeks) confirmed by TRD-C.
  • Stable antidepressant treatment for ≥6 weeks prior to baseline until follow-up.
  • HAM-D17 score ≥19 at screening and Visit 2a.
  • For females of childbearing potential: willingness to use highly effective contraception from consent until 28 days after last IP.
  • For male subjects with partner of childbearing potential: use adequate contraception or sexual abstinence from consent until 28 days after last IP.
  • Outpatient at Visit 2a.

Exclusion Criteria

  • Known hypersensitivity/intolerance to ketamine or excipients.
  • Inability to swallow the IP whole.
  • Pregnant or lactating females.
  • Significant risk of suicide (C-SSRS items 4 or 5 positive, suicidal behaviour within past year, or clinically identified significant suicidal risk).
  • Current ongoing psychiatric/neurological conditions: MDD with psychotic features, schizophrenia spectrum or other psychotic disorders, bipolar disorder, other specified disorders; first-degree relatives with psychotic or bipolar disorders also excluded.
  • Certain personality disorders (paranoid, schizoid, antisocial, borderline, histrionic, narcissistic) and moderate–severe intellectual disability/autism spectrum as specified.
  • History of significant CNS disease, surgery, encephalitis, meningitis, degenerative CNS disorder, epilepsy (except uncomplicated childhood febrile seizures).
  • Significant head trauma within past 2 years.
  • History of cerebrovascular event or known/suspected cardiac disease or ECG abnormalities that jeopardise safety.
  • Family history of sudden cardiac death in first-degree relatives.
  • Untreated/uncontrolled hypertension (systolic ≥160 mmHg or diastolic ≥90 mmHg after 5 min rest).
  • Liver function abnormalities (ALT/AST/GGT/AP >2×ULN or total bilirubin >1.5×ULN) unless discussed with medical monitor.
  • Known hepatitis B or C.
  • eGFR <60 mL/min/1.73 m2 or creatinine >200 µmol/L, dialysis or kidney transplant.
  • Uncontrolled diabetes (HbA1c >8.0%).
  • Unstable thyroid disease as specified.
  • History (within 5 years) of complicated cystitis.
  • Previous administration of ketamine or esketamine within 1 year prior to Visit 1.
  • Moderate to severe alcohol use disorder or substance use disorder (except nicotine/caffeine) within 6 months or positive drug screen (except allowed meds).
  • Use of other investigational products within specified windows or participation in ≥2 MDD/psychiatric trials within 1 year.
  • Employees/family of investigator, sponsor, CRO or consultants; persons committed by judicial order.
  • Known or suspected eye globe injury or increased intraocular pressure (eg, glaucoma).

Study Details

Locations

Germany

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