KETIVTRD2002 Phase 2a, double-blind, randomized, placebo-controlled, parallel group, dose frequency study of ketamine in subjects with treatment-resistant depression
A double-blind, randomized, placebo-controlled, parallel group, dose frequency study of ketamine in subjects with treatment-resistant depression.
Ketamine (JNJ-644059) is a racemate of R-(-)-ketamine and S-(+)-ketamine. Ketamine is an approved medication in the USA for the induction of general analgesia and for use in addition to other anesthetics. It is an anesthetic for diagnostic procedures and short lasting surgery.
The efficacy of the ketamine racemate has been successfully evaluated in subjects with treatment-resistant depression (TRD). The objective of this study is to explore the optimal dose frequency of ketamine in this population.
The study will consist of 3 phases: a screening phase of up to 4 weeks, a 4-week double-blind treatment phase (Day 1 to Day 29), and a 3-week post treatment (follow up) phase.
On Day 1, 56 subjects will be randomized to receive over 4 weeks either i.v. infusions of placebo 2 times weekly or i.v. infusions of placebo 3 times weekly or i.v. infusions of ketamine 0.50 mg/kg, 2 times weekly or i.v. infusions of ketamine 0.50 mg/kg, 3 times weekly.
Each potential subject must satisfy all of the following criteria to be enrolled in the study. Each subject must:
1. Be a man or woman, 18 to 64 years of age, inclusive.
2. Be medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel [including liver enzymes, other specific tests], hematology, serology or urinalysis are outside the normal reference ranges, a retest is allowed once. The subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
3. Meet Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV-TR) diagnostic criteria for recurrent MDD, without psychotic features (DSM-IV, 296.32, or 296.33), based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI). In addition, their major depressive episode must be deemed "valid" using the SAFER criteria interview and MGH-ATRQ confirmed by remote, independent raters (dually qualified).
4. Have an inadequate response to at least 1 antidepressant in the current episode of depression and at least one other inadequate treatment response to an antidepressant either in the current episode or in a previous episode (i.e., subject took the antidepressant at an adequate dose and for an adequate duration), assessed using the Massachusetts General Hospital – Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and medication history.
5. Have an IDS-C30 total score ≥ 34 at Screening and predose at Day 1.
6. Inpatient or agreed to be admitted to the clinic on each dosing day.
7. If a woman, before entry she must be:
Postmenopausal, defined as >45 years of age with amenorrhea for at least 18 months Menstrual Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or If heterosexually active, practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel), or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or Not heterosexually active.
Women must agree to continue using these methods of contraception throughout the study and for at least 3 months after receiving the last dose of study medication.
If a woman of childbearing potential, she must have a negative serum -human chorionic gonadotropin (-hCG) pregnancy test at screening; and a negative urine pregnancy test on Day 1 prior to randomization.
9. If a man and heterosexually active with a woman of childbearing potential, he must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.
10. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
11. Sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
12. Sign a separate written informed consent form for Part 1 of pharmacogenomic research (required), and indicate either consent or refusal for Part 2 of genetic analyses [DNA storage (optional)]. Refusal to participate in Part 2 will not result in ineligibility for the main part of the study.