A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients

A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients: Part I Dose Escalation

The purpose of this study is to evaluate the safety and the effective doses of PDC-1421 in cancer patients with depression.

Eligibility Criteria

• 21 to 85 Years of age
• Diagnosis of Stage I, II or III cancer
• Histologically-proven malignancy
• Receiving or within one year of having received cancer treatment with radiation and/or chemotherapy
• Montgomery and Åsberg Depression Rating Scale (MADRS) ≥ 20 (moderate to severe depressive symptoms)
• Duration of depressive symptoms ≥ 2 weeks by patient report.
• No active/acute suicidality requiring immediate care or psychiatric hospitalization
• Sufficient English language proficiency to complete all assessments without assistance
• Able to swallow pills
• No severe anemia, defined as hemoglobin < 10 g/dL
• No history of multiple adverse drug reactions or allergy to study drugs
• Not pregnant
• No history of head trauma
• No history of epilepsy
• No other concurrent antidepressant medications

Exclusion Criteria

• Have a current or previous diagnosis of or history consistent with obsessive-compulsive disorder, posttraumatic stress disorder, bipolar I or II, manic or hypomanic episodes, schizophrenia, major Axis II disorders which might compromise the study, or major depression with psychotic symptoms, as assessed using the MINI International Neuropsychiatric Interview (MINI Plus).

• Have a documented history of an intellectual disability.

• Use of any antidepressant medication in the last 2 weeks before visit 1 (4 weeks for fluoxetine).

• Currently being treated with tamoxifen.

• Subjects who were non-responsive to two or more courses of antidepressant medications given at an adequate dosage* for symptom treatment within four weeks, or by the judgment of the investigator considered to have treatment resistant depression (TRD), or a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or psychosurgery within the last year.

• Have a history of any seizure disorder.

• Any clinically significant abnormal vital sign, ECG, or laboratory values as determined by the investigator which might interfere with the study.

• Have a high suicidal risk as assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). High suicidal risk is indicated by:

  1. A positive response to question 4 or 5, indicating endorsement of suicidal ideation with at least some intent to act in the past month; and/or
  2. A positive response to part two of question 6, indicating the presence of any suicidal behavior in the past 3 months.

• Have a history of substance dependence/abuse** within the past 6 months or a positive drug screen result during the screening period.

• Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions.

• * An adequate dosage of the antidepressant medication is defined as the average of the usual dose (mg/day) recommended in American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition. E.g. the usual dose of Citalopram is 20-60 mg/day, the adequate dosage is 40 mg/day.

• ** Tobacco is excluded here, and alcohol abuse is defined as average pure alcohol intake is more than 112 g (for male) or 56 g (for female) per week and/or with Alcohol withdrawal syndrome. Pure alcohol intake =% (Concentration or alcohol content) x c.c. (volume)x 0.79 (density of alcohol). Result of serum ethanol test should be equal to or lower than 10.0 mg/dL to be determined as eligible for the trial. If test result is between 10.1 to 29.9 mg/dL, only one re-test is allowed per subject to meet the criterion. Subject with test result equal to or higher than 30.0 mg/dL is to be excluded.