E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of MIN-101 compared to placebo in improving the negative symptoms of schizophrenia as measured by the change from Baseline in the Positive and Negative Syndrome Scale (PANSS) negative subscale score of the pentagonal model over 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of MIN-101 compared to placebo in improving other symptoms of schizophrenia as measured by the change from Baseline in the PANSS total score, positive symptoms score, dysphoric mood, activation, and autistic preoccupation subscores of the pentagonal model over 12 weeks of double-blind treatment.
-To evaluate the efficacy of MIN-101 compared to placebo in improving symptoms of schizophrenia as measured by the change from Baseline in the PANSS total score and subscores according to the 3 factors analysis over 12 weeks of double-blind treatment.
- To evaluate the efficacy of MIN-101 compared to placebo in improving negative symptoms of schizophrenia as measured by the change from Baseline in the Brief Negative Symptoms Scale (BNSS) total score over 12 weeks of double-blind treatment.
- To assess the effects of MIN-101 compared to placebo on the CGI-S and CGI-I over 12 weeks of double-blind treatment.
For futher information please see protocol section 2 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient or patient's legal representative has provided informed consent.
2. Male or female patient, 18 to 60 years of age, inclusive.
3. Patient meets the diagnostic criteria for schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), as established by a full psychiatric interview in conjunction with the Mini International Neuropsychiatric Interview (MINI).
4. Patient is stable in terms of positive symptoms of schizophrenia over the last 3 months according to his or her treating psychiatrist
5. Patient is stable in terms of negative symptoms of schizophrenia over the last
3 months according to his or her treating psychiatrist
6. Patient with PANSS negative subscore of at least 20.
7. Patient with PANSS item score of <4 on:
-P4 Excitement, hyperactivity
- P7 Hostility
- P6 Suspiciousness
- G8 Uncooperativeness
- G14 Poor impulse control
8. Patients can be on any psychotropic as long as the psychotropic can be discontinued at the beginning of the washout phase without endangering the patient’s safety.
9. No change in any psychotropic medication during the last month (changes are allowed if done for administrative reasons or with the permission of the Sponsor’s Responsible Medical Officer).
10. No history of violence against self, others, or property.
11. Patient in whom, in the opinion of the investigator, a switch to another antipsychotic medication or initiation of an antipsychotic medication is indicated.
12. Female patient, if of childbearing potential, must test negative for pregnancy and must be using a double barrier contraceptive method.
13. Patient must be extensive metabolizers for P450 CYP2D6, as determined by genotyping test before the first drug dose is administered.
14. Patient must be able to understand the nature of the study.
15. The patient is considered by the investigator to be reliable and likely to cooperate with the assessment procedures. |
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E.4 | Principal exclusion criteria |
1. Current bipolar disorder, panic disorder, obsessive compulsive disorder, or evidence of mental retardation.
2. Patient’s condition is due to direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition.
3. Significant risk of suicide or attempted suicide, or of danger to self or others.
4. Patient has a history of substance abuse within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
5. Positive urine drug screen except when related to prescribed benzodiazepines and opiates recently prescribed for an episode of acute pain (e.g., dental extraction).
6. Patient who cannot be discontinued from psychotropics other than those allowed.
7. Patient who received clozapine within 6 months of the Screening visit. [Country-specific exception: For patients in Russia, a dose of ≤ 100 mg/day for the treatment of insomnia is allowed.]
8. Patient receiving treatment with depot antipsychotic medication can be enrolled in the study 4 weeks after the last injection.
9. Patient with a history of significant other major or unstable neurological, neurosurgical (e.g., head trauma), metabolic, hepatic, renal, hematological,
pulmonary, cardiovascular, metabolic, gastrointestinal, or urological disorder.
10. Patient with a history of epilepsy seizure disorder (patient with a history of childhood febrile seizure may be enrolled in this study).
11. Patient who has had electroconvulsive therapy (ECT), vagal nerve stimulation (VNS), or repetitive trans-cranial magnetic stimulation (r-TMS) within the 3 months prior to the Screening visit or who are scheduled for ECT, VNS, or r-TMS at any time during the study.
12. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit.
13. Body Mass Index (BMI) > 35.
14. Current systemic infection (e.g., Hepatitis B virus [HBV], Hepatitis C virus [HCV], human immunodeficiency virus [HIV], tuberculosis [TB]). Patients with positive Hepatitis B core antibody test and negative Hepatitis B Surface Antigen (HBsAg) may be included in the study if aminotransferase levels (alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) and aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) do not exceed 2 times upper limit of normal (ULN).
15. Patient who requires or may require concomitant treatment with any other medication likely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
16. Patient who requires medication inhibiting the CYP 2D6. 17. Patient with a clinically significant electrocardiogram (ECG) abnormality that could be a safety issue in the study, including QT interval value corrected for heart rate using the Fridericia’s formula (QTcF) > 430 msec for males and > 450 msec
for females.
18. Patient with a history of myocardial infarction based on medical history or ECG findings at Screening.
19. Familial or personal history of long QT syndrome or with additional risk factors for torsade de Pointes (e.g., hypokalemia, hypomagnesemia).
20. Woman of child-bearing potential, or man, who are unwilling or unable to use accepted methods of birth control.
21. Woman with a positive pregnancy test, is lactating, or is planning to become pregnant during the study.
22. Patient who participated in another clinical study within 3 months prior to Screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in PANSS negative subscale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Weeks 2, 4, 8, 12 |
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E.5.2 | Secondary end point(s) |
Change from baseline in the PANSS total score and Positive, Dysphoric mood, Activation, and Autistic preoccupation subscores of the pentagonal model
Change from Baseline in the PANSS total score and subscores according to the 3 factors analysis
Change from baseline in the Brief Negative Symptoms Scale
Change from baseline in Brief Assessment of Cognition in Schizophrenia
Change from baseline in CGI-S and CGI-I
Safety and tolerability (assessed through physical examination, adverse event reporting, electrocardiogram, vital signs assessment, Sheehan suicidality scale, Abnormal Involuntary movement Scale )
Persistence of efficacy, and the safety and tolerability of MIN-101 during the 24-week, open-label extension phase.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For: Change from baseline in the PANSS total score and Positive, Dysphoric mood, Activation, and Autistic preoccupation subscores of the pentagonal model- Baseline and Weeks 2, 4, 8, 12
For: Change from Baseline in the PANSS total score and subscores according to the 3 factors analysis-and Change from baseline in the Brief Negative Symptoms Scale - Baseline and Weeks 2, 4, 8, 12
For: Change from baseline in Brief Assessment of Cognition in Schizophrenia- Baseline and Weeks 4 and 12
For: Change from baseline in CGI-S and CGI-I-Baseline and Weeks 4, 8, 12
For: Safety and tolerability (assessed through physical examination, adverse event reporting, electrocardiogram, vital signs assessment, Sheehan suicidality scale, Abnormal Involuntary movement Scale ) - over 12 weeks of treatment
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |