Investigation of the safety , tolerability and potential therapeutic effects of JNJ-40411813 in patients with schizophrenia

• Register: EUCTR
• Last refreshed on: 13 May 2013
• Main ID: EUCTR2010-023369-23-BG
• Date of registration: 18/04/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: Investigation of the safety , tolerability and potential therapeutic effects of JNJ-40411813 in patients with schizophrenia
• Scientific title: FIRST-IN-PATIENT STUDY TO ASSESS THE SAFETY AND TOLERABILITY AND TO EXPLORE THE POTENTIAL THERAPEUTIC EFFICACY OF A NOVEL GLUTAMATE MODULATOR AS MONOTHERAPY AND AS ADD-ON THERAPY IN PATIENTS WITH SCHIZOPHRENIA - N/A
• Date of first enrolment: 28/08/2012
• Target sample size: 105
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023369-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Austria, Belgium, Bulgaria, Germany, Spain

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen Research and Development, a Division of Janssen Pharmaceutica NV

• Name: Clinical Registry Group
• Affiliation: Janssen Research and Development, a Division of Janssen Pharmaceutica NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female between 18 and 65 years of age, inclusive

2. Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive (BMI = weight/height2)

3. Medically stable on the basis of physical examination, medical history, vital signs and 12-lead ECG performed at screening.

4. Medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to not be 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.

5. In- or outpatients who have been diagnosed with schizophrenia according to DSM-IV (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year prior to screening.

6. Known by the recruiting or referring psychiatrist for at least 12 months.

7. Men must agree to use a double barrier method of birth control at each sexual intercourse (at least a condom) and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.

8. Women must meet one of the following:
– postmenopausal (amenorrhoea for at least 12 months prior to screening or amenorrhoea for at least 6 months prior to screening and follicle stimulating hormone [FSH] concentrations of >40 mIU/mL),
– surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
– or if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception at least 3 months after the last intake of study drug.

9. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving the study drug.

10. Must be able and willing to describe subjective experiences while receiving JNJ-40411813.

11. Subjects themselves or the relatives they are living with have to be reachable by phone on a regular basis.

12. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

13. Must have agreed to frequent blood sampling during the course of the study.

14. Subjects must have signed 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. In addition, subjects must have signed a separate written ICF for pharmacogenomic (DNA) research indicating consent or refusal to participate in the optional pharmacogenomic component of the study.

Inclusion criteria specific to Acute Subjects (Part A, JNJ-40411813 monotherapy)

15. Total PANSS score: 70 to 120

16. Subjects dissatisfied with current treatment and therefore accepting treatment with an antipsychotic with a novel mode-of-action over currently available antipsychotics. Such subjects should not have received any oral antipsychotic for at least 5 days, and no long acting injectable antipsychotic for at least 3 months, before Day 1.
Exclusion criteria:
1. A current DSM-IV axis I diagnosis other than schizophrenia

2. A DSM-IV diagnosis of substance abuse or dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary; subjects with a positive drug screen at screening may be included provided use does not lead to a DSM-IV diagnosis of substance dependence and subjects should be encouraged to abstain from alcohol and illegal drugs within 3 days prior to Day 1 and at any time during the study)

3. Any medical condition that could potentially alter the absorption, metabolism, or excretion of the study medication, such as Crohn’s disease, liver disease, or renal disease

4. Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular disorders), renal, hepatic, endocrine, or immunologic diseases

5. PANSS score <50 or >120

6. Other significant and/or unstable systemic illnesses

7. Allergy or hypersensitivity to any known antipsychotic compounds

8. Inability to swallow the study medication whole with the aid of water (subjects may not chew, divide, dissolve, or crush the study medication, as this may affect the release profile)

9. Subjects who have never been treated with antipsychotics

10. Exposure to an experimental drug or experimental medical device within 90 days before screening

11. Significant risk of suicidal or violent behavior

12. Female subjects who are pregnant or breastfeeding

13. Clinically significant abnormal values for clinical chemistry, hematology or urinalysis at screening or admission. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable. Values of ALT/AST <2 fold the upper limit of normal will be allowed

14. Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or HIV antibodies at screening

15. Clinically significant abnormal physical examination, vital signs or 12-lead ECG at screening. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable.

16. Clinically significant abnormal observations in ECG defined as:
– A confirmed screening visit QTcB interval =470 msec
– A history of additional risk factors for torsades des pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)

17. Use of monoamine oxidase inhibitors within 4 weeks or fluoxetine within 5 weeks before screening. Use of all tricyclic antidepressants within 2 weeks before screening

18. Use of mood stabilizers (e.g., anticonvulsants and/or lithium) within 2 weeks before Day 1.

19. Received electroconvulsive therapy within 3 months before screening

20. Have been involuntarily committed to psychiatric hospitalization

21. Alcohol dependence and/or illicit drug use

22. Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements

23. Donation of 1 or more units (approximately 450 mL) of blood or acute loss of an equivalent amount of blood within 90 days prior to study drug administration

24. Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Schizophrenia
MedDRA version: 15.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: JNJ-40411813-AAA-capsule-50 mg
Product Code: JNJ-40411813
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not assigned
CAS Number: 1127498-03-6
Current Sponsor code: JNJ-40411813-AAA
Other descriptive name: R600737
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Secondary objectives:

- To assess the pharmacokinetics of JNJ-40411813 in a patient population using a population PK approach and explore its relationship with efficacy (e.g., change in Positive and Negative Syndrome Scale [PANSS] scores) and safety parameters

Timepoint(s) of evaluation of this end point: Please refer to time and events schedule in protocol (pg 13)

Main Objective: The primary objectives of this study are to investigate, with JNJ-40411813 as monotherapy or as add-on to antipsychotics:

- Safety and tolerability in subjects with schizophrenia;
- Explore potent effect in subjects with schizophrenia;

Primary end point(s): Efficacy Endpoints:
Potential clinical efficacy of JNJ-40411813 will be evaluated using the PANSS, Clinical Global Impression- Schizophrenia scale (CGI-SCH) and the short version of the Subjective Well-Being under Neuroleptics Scale (SWN) for all the subjects. Some scales will only be used for the stable subjects who are clinically judged as
having relevant symptoms in the evaluated dimensions; the Calgary Depression Scale for Schizophrenia (CDSS), the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

Safety Endpoints:
Safety and tolerability scales for all subjects will include the Udvalg for Klinische
Undersogelser (UKU) side effect rating scale, vital signs, body weight, lab tests (including biomarkers and prolactin [PRL]) and a suicidality scale (Columbia Suicide Severity Rating Scale [CSSRS]).

Furthermore, a detailed written report on each subject will be prepared by the investigator based on her/his observations and an interview with the subject at the end of the trial. These narratives will be used to support the efficacy evaluation.

Secondary Outcome(s)

Secondary end point(s): not applicable

Timepoint(s) of evaluation of this end point: not applicable

Secondary ID(s)

40411813SCH2001

2010-023369-23-DE

Source(s) of Monetary Support

Janssen Research and Development, a Division of Janssen Pharmaceutica NV